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MS TREATMENTS: COPAXONE

 
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agate
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PostPosted: Sat Jul 15, 2006 6:29 pm    Post subject: MS TREATMENTS: COPAXONE Reply with quote

Here's a place to discuss Copaxone if you're on it or thinking about trying it or if you've been on it in the past.
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ewizabeth



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PostPosted: Mon Sep 11, 2006 6:10 pm    Post subject: Reply with quote

Copaxone Tip

If you are on C, do not take large doses of fish oil, unless checking with your doctor. I take one gram per day, but upped it to two grams while on vacation. I am still getting big bruises with most of my shots.

Thinking I should stop the fish oil for a week until I get back to normal. My PCP is going to freak out if my blood levels are off whack when I go for my checkup in a few weeks. He is always afraid I'm going to have leukemia. pale
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Ewizabeth
DX 01/28/03 RRMS
Formerly Avonex, Rebif & Copaxone
Tysabri 06/07 through 09/09
On Copaxone again since 12/09 and hoping for oral meds to come out!
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lady_express_44



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PostPosted: Tue Sep 12, 2006 9:24 am    Post subject: Reply with quote

Interesting!

Thanks for sharing that tip.

Cherie
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ewizabeth



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PostPosted: Tue Sep 12, 2006 9:46 am    Post subject: Reply with quote

You're welcome Cherie!



Another Copaxone Tip I learned today.

From Shared Solutions, somebody had this GREAT idea.

Scan in the injection map from the package insert, enlarge it, brighten it, then print out in 8X10" size sheets to mark out your weekly shot plan.

I just did it and have the .jpg file if anyone is interested.

It will be easy to remember which sites I have used recently, since I have stopped using my sensitive arms.

PM me if you want the file to print out.
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Ewizabeth
DX 01/28/03 RRMS
Formerly Avonex, Rebif & Copaxone
Tysabri 06/07 through 09/09
On Copaxone again since 12/09 and hoping for oral meds to come out!
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Not Red5_bc



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PostPosted: Tue Sep 12, 2006 10:28 am    Post subject: Reply with quote

Tip:

Take it out of the fridge about 10 minutes before you plan on injecting (or warm it up under your arm). Room temperature injections don't sting nearly as much.
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agate
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PostPosted: Mon Oct 16, 2006 1:53 pm    Post subject: A new version of Copaxone on the horizon? Reply with quote

From the ECTRIMS conference in Madrid, September 2006:

Quote:
Immunomodulation of experimental autoimmune encephalomyelitis by the novel copolymer PI-2301

B. Carrillo-Rivas, J.T. Kovalchin, J. Krieger, M. Augustyniak, I. Dufour, K. Johnson, H.M. Genova, K. Rafuse, A. Ward, S. Baldwin, R. Kolbeck, J-C. Gutierrez-Ramos, E. Zanelli (Cambridge, USA)

Years of clinical experience have shown that daily subcutaneous administration of the peptide copolymer Copaxone™ (Cop-1), a mixture of millions of peptides composed of the four amino acids YEAK in random order, is a safe and efficacious treatment for relapsing-remitting multiple sclerosis (RR-MS).

Cop-1 was modeled to mimic myelin basic protein (MBP) and turned out to ameliorate experimental autoimmune encephalomyelitis (EAE) in mice, most likely by shifting the immune response away from an effector TH1 to an immunoregulatory TH2/TH3 immune response through presentation by MHC class II molecules.

Recently, a series of new peptide copolymers have been synthesized with the goal to improve the in vivo efficacy of Cop-1. In the present study, we show that Copolymer PI-2301 produced by substituting E with F has improved beneficial effects in a relapsing-remitting murine model of EAE.

Unlike Cop-1, PI-2301 shows long-term therapeutic efficacy when administered either daily or weekly at disease onset. In an adoptive EAE setting, efficacy of PI-2301 administered daily at the time of autoreactive lymph node cell transfer correlates with decreased serum level of Metalloproteinase-9 and increased level of Metalloproteinase Inhibitor-1.

Antibody production against PI-2301 and T-cell recall proliferation assay using splenocytes from PI-2301-treated mice underscore the induction of a TH2/TH3 immunity. Evidences of the expansion of T-cells with regulatory properties expressing Forkhead box protein P3 (FoxP3) and producing Interleukin-10 following PI-2301 treatment are also apparent.

We propose that PI-2301 is a potential novel immunomodulatory compound for the treatment of RR-MS. Clinical trials will soon be started to test this hypothesis.
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LoLo



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PostPosted: Sat Nov 04, 2006 7:15 pm    Post subject: Reply with quote

ewizabeth wrote:
Copaxone Tip

If you are on C, do not take large doses of fish oil, unless checking with your doctor. I take one gram per day, but upped it to two grams while on vacation. I am still getting big bruises with most of my shots.

Thinking I should stop the fish oil for a week until I get back to normal. My PCP is going to freak out if my blood levels are off whack when I go for my checkup in a few weeks. He is always afraid I'm going to have leukemia. pale


E -

I've never heard this - why is that? I had been recently contemplating trying to find a good fish oil supplement to take, as everyone seems to believe it's so good for PWMS in particular.
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ewizabeth



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PostPosted: Sat Nov 04, 2006 8:40 pm    Post subject: Reply with quote

Quote:
I've never heard this - why is that? I had been recently contemplating trying to find a good fish oil supplement to take, as everyone seems to believe it's so good for PWMS in particular.


Lolo,

Fish oil is a blood thinner. If you read about it at the AMA.org (I think that's the site for American Heart Association...) it tells you to guard against high doses unless you're being monitored by a doctor. Too much thinning of the blood can cause bleeding problems or strokes. It can be very serious. I take a 1 gram fish oil cap with enteric coating. I also take one small cod liver oil cap for the natural A & D combo.
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Ewizabeth
DX 01/28/03 RRMS
Formerly Avonex, Rebif & Copaxone
Tysabri 06/07 through 09/09
On Copaxone again since 12/09 and hoping for oral meds to come out!
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LoLo



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PostPosted: Thu Nov 09, 2006 5:26 pm    Post subject: Reply with quote

EEKS. Thanks!
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ewizabeth



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PostPosted: Thu Nov 09, 2006 7:42 pm    Post subject: Reply with quote

You're welcome! It's one of those innocent looking supplements that can cause real problems at high doses.
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Ewizabeth
DX 01/28/03 RRMS
Formerly Avonex, Rebif & Copaxone
Tysabri 06/07 through 09/09
On Copaxone again since 12/09 and hoping for oral meds to come out!
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agate
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PostPosted: Tue Nov 14, 2006 3:23 pm    Post subject: (Abstract) Panniculitis from subQ Copaxone injections Reply with quote

From PubMed, 11/14/06:

Quote:
J Am Acad Dermatol. 2006 Jun 21;55(6):969-975

Localized panniculitis secondary to subcutaneous glatiramer acetate injections for the treatment of multiple sclerosis: A clinicopathologic and immunohistochemical study

Soares Almeida LM, Requena L, Kutzner H, Angulo J, de Sa J, Pignatelli J.
From the Departments of Dermatology and Neurology. [Clinica Universitaria de Dermatologia, Hospital de Santa Maria, Lisboa, Portugal]

BACKGROUND
: Glatiramer acetate has been shown to be effective in reducing the relapse and improving the disability of patients with multiple sclerosis. The most common adverse effects at the injection sites include pain, inflammation, and induration that spontaneously disappear within hours or a few days.

OBJECTIVE: We sought to characterize the histopathologic findings of localized panniculitis induced by glatiramer acetate at the injection sites.

METHODS
: Seven patients receiving daily glatiramer acetate injections for treatment of multiple sclerosis developed localized panniculitis at the injection sites. The lesions were histopathologically and immunohistochemically studied.

RESULTS: The lesions consisted of a mostly lobular panniculitis, with lipophagic granuloma, namely histiocytes engulfing the lipids from necrotic adipocytes. In many areas, scattered neutrophils and eosinophils were seen both in the septa and in the fat lobules. Connective tissue septa showed widening and fibrosis in conjunction with many lymphoid follicles, presenting with germinal center formation. Immunohistochemically, the inflammatory infiltrate of the fat lobule consisted of CD68(+) histiocytes and suppressor/cytotoxic T lymphocytes. In contrast, the lymphoid follicles in the septa and at the interface between septum and fat lobule were mainly composed of B lymphocytes.

LIMITATIONS: Only one biopsy was performed in each patient and, therefore, it was not possible to study the histopathologic evolution of the panniculitic process.

CONCLUSIONS: Localized panniculitis at the sites of subcutaneous injections of glatiramer acetate for treatment of multiple sclerosis seems to be a rare, but characteristic side effect of this therapy. The histopathologic pattern of these lesions consists of a mostly lobular panniculitis, with histiocytes and T lymphocytes in the fat lobule and thickened septa with scattered lymphoid follicles, which are mostly composed of B lymphocytes.



Panniculitis is
Quote:
an inflammatory reaction of the subcutaneous fat, which may involve the connective tissue septa between the fat lobes, the septa lobules and vessels or the fat lobules, characterised by the development of single or multiple cutaneous nodules.
--according to an online medical dictionary.
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PostPosted: Wed Jan 31, 2007 2:59 pm    Post subject: (Abstract) Copaxone in PPMS: Results of a ...trial Reply with quote

From PubMed, January 31, 2007:

Quote:
Ann Neurol. 2007 Jan 29;61(1):14-24

Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double-blind, placebo-controlled trial

Wolinsky JS, Narayana PA, O'connor P, Coyle PK, Ford C, Johnson K, Miller A, Pardo L, Kadosh S, Ladkani D.
Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX.

OBJECTIVE: To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis.

METHODS:
A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3-year, double-blind trial. The primary end point was an intention-to-treat analysis of time to 1- (entry expanded disability status scale, 3.0-5.0) or 0.5-point expanded disability status scale change (entry expanded disability status scale, 5.5-6.5) sustained for 3 months. The trial was stopped after an interim analysis by an independent data safety monitoring board indicated no discernible treatment effect on the primary outcome. Intention-to-treat analyses of disability and magnetic resonance imaging end points were performed.

RESULTS: There was a nonsignificant delay in time to sustained accumulated disability in GA- versus PBO-treated patients (hazard ratio, 0.87 [95% confidence interval, 0.71-1.07]; p = 0.1753), with significant decreases in enhancing lesions in year 1 and smaller increases in T2 lesion volumes in years 2 and 3 versus PBO. Post hoc analysis showed that survival curves for GA-treated male patients diverged early from PBO-treated male subjects (hazard ratio, 0.71 [95% confidence interval, 0.53-0.95]; p = 0.0193).

INTERPRETATION: The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated. Ann Neurol 2007;61:14-24.

PMID: 17262850


More on this study from Neura.net, April 27, 2007:

Quote:
Study Analysis Suggests PROMiSe in Men With Primary-Progressive Multiple Sclerosis

Wolinsky JS, Narayana PA, O'Connor P, et al., and the PROMiSe Trial Study Group.

Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007;61:14-24. [PubMed]

Primary-progressive multiple sclerosis (PPMS) is a relatively uncommon but devastating form of MS. Unlike the other forms, PPMS lacks a remission phase. From onset, PPMS advances unremittingly, producing accumulated neurologic disability throughout its course. Because of its relentless nature, PPMS may be an appropriate model for studying the effect of a drug on MS progression without the confounding effects of remission.

In a 1991 trial,1 15 mg of subcutaneous glatiramer acetate (GA; Copaxone) twice daily delayed time to disease progression in patients with "chronic progressive" MS, of whom 27.7% were later found to have PPMS. Recently, Jerry Wolinsky, MD, and colleagues in the PROMiSe Study Group designed a 3-year, multinational, randomized, double-blind, placebo-controlled study of GA in PPMS (n=943) to determine whether 20 mg of subcutaneous GA daily increases the time delay to sustained disability progression, with the change in disability indicated by a 1.0- or 0.5-point change in Expanded Disability Status Scale (EDSS) score; patients had baseline scores of 3.0 to 5.0 (stratum I) or 5.5 to 6.5 (stratum II), respectively.

The rate of disability progression during the first 12 months of the study was much slower than predicted: stratum I had a 16.1% rate of EDSS progression in both treated and placebo groups vs the predicted rate of 50%; stratum II had a 19.3% rate of EDSS progression in both treated and placebo groups vs the predicted rate of 20%. The study was discontinued at 24 months based on the recommendations of the data safety monitoring board, which felt that the study protocol would not detect a significant effect. Participants were allowed to remain in the study, however, as part of a 12-month natural history extension.

During the 2 years of active treatment, the GA group demonstrated a tendency for prolonged time to both sustained disability progression and mean EDSS score increase from baseline vs placebo, but neither effect reached statistical significance. However, the number of gadolinium-enhancing lesions seen on magnetic resonance imaging in the treated group decreased significantly compared with the placebo group (P = 0.0022) during the first year; this difference became borderline at 24 months (P = 0.0702), and disappeared at 36 months.

Post hoc analyses to determine whether disease progression rates varied among subpopulations of the study revealed that the delay in disease progression compared with placebo was significant in men (P = 0.0193), but not in women (P = 0.6304). An intention-to-treat analysis revealed a study population closely resembling a PPMS population, ie, increased male:female ratio, older age at onset (mean: 39 years), and similar time to first diagnosis (9.8 and 12.1 years for EDSS scores 3.9 and 6.2, respectively). Postanalysis recommendations, eg, for an alternative definition of "sustained progression of disability" and alternative criteria for evaluating neurologic function tests, may result in protocols with improved sensitivity to GA benefits in PPMS in future studies.

Reference


1. Bornstein MB, Miller A, Slagle S, et al. A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Neurology. 1991;41:533-539. [PubMed]



Last edited by agate on Fri Apr 27, 2007 3:21 pm; edited 1 time in total
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ewizabeth



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PostPosted: Thu Feb 01, 2007 7:37 pm    Post subject: Reply with quote

Well, hopefully they'll find something good that will work soon. Maybe one of the vaccine type treatments will work. After they get them more perfected, they might be able to custom design for PPMS patients too. Anyway, just wishful thinking ....
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PostPosted: Wed Mar 14, 2007 6:57 pm    Post subject: (Abstract) Copaxone w/minocycline versus Copaxone alone Reply with quote

Scheduled for the upcoming AAN conference in May:

Quote:
[S02.003] Glatiramer Acetate Combined with Minocycline Reduces the Number of T1 Gd-Enhancing and New T2 Lesions Compared to Glatiramer Actetate Alone

Luanne Metz, David Li, Anthony Traboulsee, Vancouver, BC, Canada, Mary Myles, Edmonton, AB, Canada, Pierre Duquette, Jean Godin, Montreal, QC, Canada, Michel Constantin, Montreal, PQ, Canada, V. Wee Yong, Calgary, AB, Canada

OBJECTIVE: To evaluate the add-on effect of minocycline in subjects initiating treatment with GA.

BACKGROUND: Glatiramer acetate (GA) reduces clinical and MRI activity in relapsing-remitting multiple sclerosis (RRMS). Recently minocycline was shown to reduce enhancing MRI activity in a pilot trial. Animal studies support an increased benefit from the combination.

DESIGN/METHODS: RRMS patients (n=44) with one or more T1-enhancing lesions on their screening MRI were randomized to either GA 20 mg daily + minocycline 100 mg twice daily or GA + placebo. Subjects were assessed clinically and by MRI at screening and months 1, 3, 8 and 9. The primary outcome was the total number of T1 enhancing lesions at months 8 and 9.

RESULTS: Forty subjects completed the study. Two subjects from each group discontinued study drug. Groups were balanced clinically at baseline except for greater T1-enhancing lesion number in the GA/minocycline group (median 3 versus 2; mean 7.62 versus 2.43 (p=0.07)). Despite this imbalance treatment favoured the GA/minocycline group. At months 8 and 9, the number of T1-enhancing lesions was reduced by 63% (mean 1.47 versus 2.95; p=0.08) and the number of new T2 lesions was reduced by 65% (mean 1.84 versus 5.14; p=0.06), compared to GA/placebo. Relapse risk was reduced by 42% in the GA/minocycline group (0.19 versus 0.41; p=NS). Treatment was safe and well tolerated.

CONCLUSIONS/RELEVANCE: A trend to significance on both primary and secondary end-points, despite imbalance at baseline, reflects a consistent pattern of benefit favoring the combination of GA and minocycline. As minocycline is a safe, well-tolerated and inexpensive therapy a further study of this combination in RRMS is warranted.

Supported by: Teva Neuroscience Canada.

Tuesday, May 1, 2007 2:30 PM

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PostPosted: Fri Mar 16, 2007 2:19 pm    Post subject: (Abstract) Copaxone alone vs. Copaxone + Novantrone Reply with quote

Scheduled for the upcoming AAN conference in May:

Quote:
[P01.046] Tracking In Vivo Immune Modulation in MS Patients Treated with Glatiramer Acetate (GA) Alone, or with GA Preceded by Mitoxantrone, Provides Novel Insights into the Mode of Action of Therapeutic Strategies That Combine Immune Suppression and Immune Deviation

Amit Bar-Or, Ebrima Gibbs, Masaaki Niino, Tariq Aziz, Sudabeh Alatab, Fu Dong Shi, Denise Campagnolo, Farzaneh Jalili, Susan Rhodes, Tami Yamashita, Boli Fan, Mark Freedman, Ottawa, ON, Canada, Hillel Panitch, Burlington, VT, Douglas Arnold, Montreal, QC, Canada, Timothy Vollmer, Phoenix, AZ, Joel Oger, Vancouver, BC, Canada

OBJECTIVE: To compare the effect of pre-treatment with a brief course of mitoxantrone [Novantrone] followed by GA [Copaxone] therapy, to treatment with GA alone, on the in vivo kinetics of GA-mediated Th2-deviation.

BACKGROUND: In a recent controlled study, GA therapy following a brief course of mitoxantrone (Mitox-GA) was more effective than GA-alone, on clinical and neuroimaging measures, including markers of inflammation (gado+ lesions) and neuroprotection (persistent black holes). Whether these improved outcomes reflect enhanced capacity for GA-mediated Th2-deviation following immune suppression has important ramifications on combination-therapy strategies.

DESIGN/METHODS: GA-induced antibodies (total-IgG; IgG1, IgG2, IgG3, IgG4) were measured serially (ELISA) in serum of n=21 consenting RRMS patients recruited during screening for the above trial. The relationship between IgG1 and IgG4 GA-reactive antibodies is a useful marker of GA-mediated Th2-deviation, as previously reported.

RESULTS: GA-reactive antibodies were undetectable pre-treatment. GA-alone induced strong GA-reactive total-IgG and IgG1-4 responses, peaking at 3 months (p<0.0001 for all), with subsequent partial decreases by 12 months in IgG1-3 (p<0.02 for all), but a significant further IgG4 increase (p=0.007), reflecting the expected GA-mediated in vivo Th2-deviation. GA therapy following mitoxantrone (3 monthly-infusions totaling 36 mg/m2), also induced GA-reactive total IgG, and IgG1-4, peaking at 3 months (p=0.018), although to lower levels than GA-only therapy. By month 12 of GA therapy in the Mitox-GA arm, IgG1-3 tended to decrease (p=0.043; p=0.028; p=0.063, respectively) while IgG4 exhibited an ongoing increasing trend (p=0.064).

CONCLUSIONS/RELEVANCE: The pre-treatment with mitoxantrone appears to partially reduce and/or delay the IgG1 to IgG4 switch characteristic of the Th1 to Th2 switch.

Taken together with the aforementioned neuroimaging observations, our results suggest the enhanced efficacy of Mitox-GA over GA-alone is not due to an enhanced Th2-shift but rather reflects combined anti-inflammatory effects of mitoxantrone and GA, and a preserved neuroprotective effect of GA. These findings will help guide future approaches combining immune-suppression and immune-deviation.


Tuesday, May 1, 2007 7:00 AM
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PostPosted: Wed Mar 21, 2007 2:07 pm    Post subject: (Abstract) Dose-comparison study of Copaxone in RRMS Reply with quote

From PubMed, 3/21/07:

Quote:
Neurology. 2007 Mar 20;68(12):939-44

Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing-remitting MS

Cohen JA, Rovaris M, Goodman AD, Ladkani D, Wynn D, Filippi M; 9006 Study Group.
Mellen Center for MS Treatment and Research, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. cohenj@ccf.org

OBJECTIVE: To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40 mg daily vs the approved 20-mg formulation in relapsing-remitting multiple sclerosis.

METHODS:
Eligibility criteria included clinically definite multiple sclerosis, Expanded Disability Status Scale score 0 to 5.0, no previous use of GA, at least one relapse in the previous year, and 1 to 15 gadolinium-enhancing (GdE) lesions on a screening MRI. MRI was repeated at months 3, 7, 8, and 9, and neurologic examinations were performed at baseline and months 3, 6, and 9.

RESULTS: Of 229 subjects screened, 90 were randomly assigned to GA 20 mg (n = 44) or 40 mg (n = 46). The groups were well matched at baseline for demographic, clinical, and MRI characteristics. The primary efficacy endpoint, total number of GdE lesions at months 7, 8, and 9, showed a trend favoring the 40-mg group (38% relative reduction, p = 0.0898). A difference between the two dose groups emerged as early as month 3 (52% reduction; p = 0.0051). There was a trend favoring the 40-mg group for relapse rate with benefit on proportion of relapse-free subjects (p = 0.0183) and time to first relapse (p = 0.0367).

GA 40 mg was well tolerated, with an overall safety profile similar to that of 20 mg. Some features of injection site reactions and immediate postinjection reactions were more common and severe with the higher dose.

CONCLUSIONS: Glatiramer acetate (GA) 40 mg was safe and well tolerated. The overall efficacy results suggested that a 40-mg dose of GA may be more effective than the currently approved 20-mg daily dose in reducing MRI activity and clinical relapses.

PMID: 17372130
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PostPosted: Fri Apr 06, 2007 5:33 pm    Post subject: Copaxone possibly useful in treating glaucoma Reply with quote

Johns Hopkins Health Alerts for April 6, 2007:

Quote:



Neuroprotection -- New Frontier in the Treatment of Glaucoma


Johns Hopkins reports on new drugs for fighting glaucoma.

Physicians have recently confirmed through large clinical studies that lowering intraocular pressure (IOP) is highly beneficial in reducing vision loss in people with glaucoma. Indeed, the lowering of IOP is the only FDA-approved approach for treating glaucoma. However, newer approaches to the treatment of glaucoma are being studied to supplement present therapy in order to reduce the progressive loss of vision in glaucoma even further.

Glaucoma researchers are investigating a number of ways to intervene in this process. Overall, their area of research is known as neuroprotection -- protecting the retinal ganglion cell from damage. Retinal ganglion cells are responsible for visual signaling from the eye to target areas in the brain, and their death is the hallmark of glaucoma. The hope of neuroprotection research is that this retinal ganglion cell loss can be slowed, or even stopped altogether.

A number of neuroprotection strategies are under investigation. Some use drugs originally developed for other conditions, such as multiple sclerosis. Some of the most promising are as follows:

Memantine (Namenda). This drug is FDA-approved for treating Alzheimer’s disease. It is taken orally and appears to protect brain cells from the damaging effects of high levels of glutamate, an amino acid. A large study of memantine in more than 2,000 people with glaucoma is currently under way; the study is expected to end next year.

Brimonidine (Alphagan). This medication is currently used in eye drop form to treat glaucoma by lowering IOP. In animal studies, oral and injected forms of bromonidine show promise as having a protective effect on the optic nerves and the retinal ganglion cells. In people, brimonidine is being tested and compared with another glaucoma drug, timolol (Timoptic) in 190 people with normal-tension glaucoma (people with IOP readings in the normal range whose glaucoma is worsening). The goal of the study is to see whether there is any difference between the two drugs in terms of visual field stability or deterioration. It is important to note that the use of brimonidine eye drops as a neuroprotectant has no definitive evidence in humans.

Glatiramer (Copaxone). This drug, normally used to treat multiple sclerosis, may protect the optic nerve by triggering a mild autoimmune response. Glaucoma researchers theorize that the autoimmune response is one way the body protects itself from injury to nerve cells. By using glatiramer, researchers hope to boost the autoimmune response to the initial damage and prevent any additional damage.


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PostPosted: Tue May 01, 2007 5:26 pm    Post subject: Reply with quote

John F. Kurtzke (the one who came up with the Kurtzke disability scale) has a comment in Journal Watch: Neurology, May 1, 2007, that concerns the study by Wolinsky et al described in the post of January 31 in this thread.

Quote:
Treatment of Primary Progressive Multiple Sclerosis

Glatiramer acetate did not have a statistically significant benefit in a study with a high dropout rate.

Wolinsky and colleagues exhaustively assessed whether glatiramer acetate (GA) can delay progression in primary progressive multiple sclerosis (PPMS). This multicenter, international, and multifaceted double-blind trial was designed to last 3 years. Clinical, laboratory, and statistical assessments were extremely thorough. Patients were classified into two strata according to Expanded Disability Scale (EDSS) score, but all post-entry data are given for the EDSS-score strata combined. There were 627 patients randomized to receive GA and 316 to receive placebo (PBO).

The second planned interim analysis of the data safety monitoring board indicated both that disease progression was much slower than expected and that the groups did not differ in the primary outcome measure. At that time, only 35 GA and 18 PBO recipients had completed 3 years of treatment, and 188 GA and 98 PBO recipients had dropped out. For the remaining 404 GA and 200 PBO recipients, the study sponsor (the drug’s manufacturer) halted the study at that point and offered "natural history" follow-up.

The intention-to-treat hazard ratio for confirmed progression in the planned 3-year study was 0.87, suggesting a drug effect, but was not significant. A post hoc analysis showed a significant effect for males (HR, 0.71) but not females (HR, 1.08). Numbers contributing to the "survival curves" for time to confirmed disease progression were 465 GA and 239 PBO recipients at 12 months; 355 GA and 175 PBO recipients at 24 months; and 68 GA and 30 PBO recipients at 36 months.

Comment: Why did this study — conducted by the most knowledgeable and experienced MS investigators extant, with a protocol that was a model for emulation — fail to meet its goal? I was struck by the large proportions of dropouts, particularly in the third year. I wonder whether the only contact with these patients after their initial assessment was during their trimonthly trek to receive the new drug packets along with their reassessments. Who took care of them in the interim? Was their total illness managed by the study centers with physiotherapy, counseling, or other treatments on a regular, ongoing basis?

I have been told that lack of proof is not proof of lack; "truth" lies in more than P<0.05, and we still must treat our patients today as best we can. I think the authors do have evidence to suggest efficacy at the 2-year point. Statistical testing for the hazard ratio up to that point might have indicated significance because dropouts were not then numerous, but the study design precluded such testing. However, the authors could have performed a post hoc analysis of the 2-year data, just as they had analyzed effects by sex — though I would not limit use of glatiramer acetate by sex. Barring anything better, this seems to me a reasonable treatment for patients with worsening PPMS, but not (yet) for those with stable illness.

— John F. Kurtzke, MD, FACP, FAAN

Dr. Kurtzke is Professor Emeritus of Neurology, Georgetown University, Washington, DC.

Published in Journal Watch Neurology May 1, 2007


Citation(s):

Wolinsky JS et al. Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 2007 Jan; 61:14-24.

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PostPosted: Fri May 25, 2007 9:04 am    Post subject: Generic Copaxone in the works Reply with quote

From Market Watch, May 20, 2007:

Quote:
Teva may face generic rival to Copaxone
By Robert Daniel, MarketWatch
Last Update: 11:41 AM ET May 20, 2007

TEL AVIV (MarketWatch) -- Teva Pharmaceutical Industries Ltd. may face its first generic competition for its first branded drug, Copaxone, a treatment for multiple sclerosis.

Natco Pharma Ltd. of Hyderabad, India, said it would launch glatiramer acetate, the generic version of Copaxone, at about 40% of the price of the branded Teva drug.

The Indian company said it would launch the drug in India, where about 50,000 people suffer from the disease.

The Israeli dailies Globes and Haaretz say that Teva's patent on Copaxone runs through 2014 in the U.S. and 2015 in other countries.

Teva is cleared to market Copaxone in 47 countries, including the U.S., Canada, Mexico, Australia, Israel, and all of Europe. The U.S. Food and Drug Administration first cleared the drug for marketing in the U.S. late in 1996.



Multiple sclerosis is thought to be an autoimmune disease in which the sheath that protects the nerve fibers in the central nervous system is destroyed. This damage disrupts the electrical impulses traveling within the nervous system. In turn, those who suffer from MS may have symptoms including trouble balancing, their speech may be slurred, and their vision may be impaired.

On its web site, Teva says that MS afflicts some 400,000 people in the U.S. and more than two million worldwide.

Copaxone, taken by daily injection, reduces the frequency of relapses of MS. Scientists have yet to figure out what causes the disease.

Teva's 2006 worldwide sales of Copaxone were $1.41 billion, up 20% from 2005. Copaxone accounted for 17% of Teva's total 2006 sales of $8.41 billion.

.........

Robert Daniel is MarketWatch's Middle East bureau chief, based in Tel Aviv.

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PostPosted: Wed May 30, 2007 11:18 pm    Post subject: Reply with quote

Tonight I finally got hold of the nurse who is going to train me in giving the Copaxone shot. She'll be here Monday afternoon for less than an hour, she says.

She says most people have no problems with the Copaxone shots. That was good to know.
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PostPosted: Mon Jun 04, 2007 6:30 pm    Post subject: Does anyone speak nurse-speak? Reply with quote

The nurse, sporting a top that had "COPAXONE" written across her pocket, arrived today, with a Copaxone shoulder bag containing some syringes set up for testing, along with a little gizmo with a rubber top, into which I could do my test injections of Copaxone.

We went through this routine, doing manual injection and autoject injection. Then I did my own shot in my right arm, using the autoject.

A few minutes later, the nurse wanted to see the injection site. She said, "Hmm, you have a nice dollar-sized wheal there."

OK, that's where I need some help. The word "nice"--does that mean "extra big" or "desirable" or what?

She was calling it a hive, too, but when I said it didn't look like the hives my daughter used to get (those were numerous and red), she said, "Well, it's not really a hive..."

She said that she's trained about 100 MS patients to do Copaxone shots. She mentioned that one of them is 80 years old.
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PostPosted: Wed Jun 06, 2007 2:16 pm    Post subject: OK to store Copaxone at room temp for up to 1 month now Reply with quote

Here's a press release, June 6, 2006:

Quote:
June 06, 2007 02:00 AM Eastern Daylight Time

COPAXONE® Pre-Filled Syringe Can Now Be Stored for up to One Month at Room Temperature

Extended Storage Provides Enhanced Convenience for Relapsing-Remitting Multiple Sclerosis (RRMS) Patients
JERUSALEM & PARIS--(BUSINESS WIRE)--Teva Pharmaceutical Industries, Ltd. and sanofi-aventis today announced that the application for up to one month room temperature storage of COPAXONE® (glatiramer acetate injection) pre-filled syringe has been approved by the U.S. Food and Drug Administration (FDA) and in Europe under the Mutual Recognition Procedure (MRP). With this supplemental amendment, COPAXONE® may now be stored by patients at room temperature for up to one month. Prior to this approval, COPAXONE® was approved for storage at room temperature for up to seven days.

Christina A., Germany, an opera singer who has been using COPAXONE® for the past six years commented: “As a performer, I spend a lot of time on tour. Transporting and storing my COPAXONE® will now be much easier.”

“For the past fifteen years, COPAXONE® has allowed me to control my disease and has granted me the ability to maintain an active lifestyle,” said Laura K., a participant in the first pivotal trial evaluating the drug. “As a competitive equestrian, I spend a lot of time away from home, and now that COPAXONE® can remain at room temperature for a longer period of time, transporting and storing it will be much easier.”



I'm going to check into this further and will update this post if needed.
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PostPosted: Wed Jun 06, 2007 6:13 pm    Post subject: Reply with quote

I called Shared Solutions and confirmed that it's now OK to store Copaxone at room temperature (under 86 degrees F.) for up to 30 days--and that goes for any Copaxone you might happen to have on hand, too.

It isn't mentioned on their Website now but my guess is that it soon will be posted there.
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PostPosted: Thu Jun 07, 2007 5:34 am    Post subject: Reply with quote

Agate:

How are you managing with the shots? I imagine you are a pro at it - are you still getting the wheals?

I used to give allergy shots, it wasn't unusual to see wheals on upper arms from the different serums.

You are really brave to try one of the CRABs. I think if it ever warrants it I'll opt for LDN.
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PostPosted: Thu Jun 07, 2007 8:40 am    Post subject: Reply with quote

Yesterday was the third shot, and I opted for the back site this time, including using the auto-ject thing. The autoject is another "procedure" to learn, and I'm more timid about using it than about the manual injecting.

Avonex didn't have an auto-inject device, at least not when I was on it, and so these are new to me though the glucose monitor I have has a similar deal for drawing blood (press a button and the needle goes in).

So far, I've just had the one wheal. If this is the way it will be, I'm very, very lucky.
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PostPosted: Thu Jun 07, 2007 7:25 pm    Post subject: Reply with quote

Hi Agate,

I always had the worst site reactions on my arms, they were typically the most tender spot.

Did the nurse explain about site rotation and moving around within each site? That is very important.
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PostPosted: Thu Jun 07, 2007 10:31 pm    Post subject: Reply with quote

She did indeed explain. In fact, when I told her that the diagrams of the injection sites are hard for me to see (and to write dates on) because they're faint and tiny, she said she'd see about getting the illustrations magnified and reproduced for people like me.

I should think this might be a problem for a number of people with less-than-perfect eyesight.
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PostPosted: Fri Jun 08, 2007 7:34 am    Post subject: Reply with quote

Agate,

If you'd like, I can scan them in, blow them up and email the file to you. I did that for myself when I was taking it. Then, when I'd do my shots, I'd just put the date in the spot, for instance, M1 for Monday the first, then Tuesday (T2) would get a different section, and so on.

Also, if you get to a spot within a section that has a lump, or is still sore or bruised, use the opposite end of that section for that day's shot as much as possible.

Doing this, I was able to handle the shot routine pretty well. Let me know if you'd like the shot map emailed to you.
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PostPosted: Fri Jun 08, 2007 8:43 am    Post subject: Reply with quote

Thanks so much! I wouldn't want to put you to the trouble of tinkering with the chart unless Shared Solutions can't come up with an enlarged chart. I'd like to give them a week or two to get it to me, since the promise was made.

And thank you for the helpful tips. It's nice to have help from experienced people who've been there and done that!
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PostPosted: Fri Jun 08, 2007 8:47 am    Post subject: Reply with quote

You're welcome!

Let me know if you'd like the shot chart, it isn't a problem and I'd be happy to do it.

I think it would be a great idea for them to do that though, for all of their patients.
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PostPosted: Fri Jun 22, 2007 8:55 am    Post subject: Reply with quote

ewizabeth, I've made up diagrams of the 7 injection locations and ruled them off with huge boxes so I can enter the dates for the shots. I remember doing this for my thighs with Avonex, and it worked fairly well. For the time being, I'm OK without the magnified chart--but thank you again.

And now a question for Copaxone users in general:

If you get a lump under your skin after a shot, I understand (from the Shared Solutions people) that that is the Copaxone itself, pooling under your skin, and that 24 hours later you can massage it to try to get it to go down.

I've been doing that, and it helps the lump to get smaller, but some lumps haven't gone away for a couple of weeks now.

If this is the Copaxone pooling there in the lump, how is the Copaxone doing its job? Isn't it supposed to be getting dispersed in your body? Does a lump mean that you're not getting any benefit from the Copaxone?
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PostPosted: Fri Jun 22, 2007 9:33 pm    Post subject: Reply with quote

agate wrote:

And now a question for Copaxone users in general:

If you get a lump under your skin after a shot, I understand (from the Shared Solutions people) that that is the Copaxone itself, pooling under your skin, and that 24 hours later you can massage it to try to get it to go down.

I've been doing that, and it helps the lump to get smaller, but some lumps haven't gone away for a couple of weeks now.

If this is the Copaxone pooling there in the lump, how is the Copaxone doing its job? Isn't it supposed to be getting dispersed in your body? Does a lump mean that you're not getting any benefit from the Copaxone?


Agate,

From my level of understanding how Copaxone works (greatly simplified for my own benefit... )

When you give yourself the shot, the medicine does disperse. But, the body initiates a sort of immune system reaction to the copaxone and this sets up sort of a decoy for the immune system to attack to get its focus away from the myelin that it attacks due to the MS. (Although they aren't exactly certain how it does its thing.)

So, that's part of the reason for the site reactions from the way I understand it.

If you have a lump from a shot in one place for two weeks, you just don't use that exact spot, even if you don't get back to that same section (within an area) for 3-4 weeks. And yes, after 24 hours you can massage the spot, and it might even be more effective if you do it in the warmth of the shower or bath.

I hope that made sense! And good luck with the Copaxone, I hope it works ok and the shots become do-able! thumbright It took me several weeks to really get a routine going with them.
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PostPosted: Fri Jun 22, 2007 10:56 pm    Post subject: Reply with quote

Thanks so much for the helpful reply!
I guess I couldn't understand how the medicine could be doing anything useful if it's just sitting there, "pooled" in that lump around the injection site. From what you say, it sounds as if it can still work even though it's all glommed together in that lump. (I apologize for my nonscientific vocabulary!)

So far, the shots are going fine. I hope this continues. Thanks for your interest!
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PostPosted: Tue Aug 07, 2007 5:46 pm    Post subject: (Abstract) Reply with quote

From PubMed, August 7, 2007:

Quote:
Nat Med. 2007 Aug 5

Type II monocytes modulate T cell-mediated central nervous system autoimmune disease

Weber MS, Prod'homme T, Youssef S, Dunn SE, Rundle CD, Lee L, Patarroyo JC, Stüve O, Sobel RA, Steinman L, Zamvil SS.
Department of Neurology and Program in Immunology, University of California, San Francisco, 513 Parnassus Avenue, S-268, San Francisco, California 94143-0435, USA.

Treatment with glatiramer acetate (GA, copolymer-1, Copaxone), a drug approved for multiple sclerosis (MS), in a mouse model promoted development of anti-inflammatory type II monocytes, characterized by increased secretion of interleukin (IL)-10 and transforming growth factor (TGF)-beta, and decreased production of IL-12 and tumor necrosis factor (TNF). This anti-inflammatory cytokine shift was associated with reduced STAT-1 signaling. Type II monocytes directed differentiation of T(H)2 cells and CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg)) independent of antigen specificity. Type II monocyte-induced regulatory T cells specific for a foreign antigen ameliorated experimental autoimmune encephalomyelitis (EAE), indicating that neither GA specificity nor recognition of self-antigen was required for their therapeutic effect. Adoptive transfer of type II monocytes reversed EAE, suppressed T(H)17 cell development and promoted both T(H)2 differentiation and expansion of T(reg) cells in recipient mice. This demonstration of adoptive immunotherapy by type II monocytes identifies a central role for these cells in T cell immune modulation of autoimmunity.

PMID: 17676050
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PostPosted: Fri Sep 07, 2007 8:45 am    Post subject: Problems with Copaxone needles? Reply with quote

LaDeeDa has just posted in another thread about a shipment of Copaxone she suspects contained blunter needles than usual.

I'd be interested in knowing if anyone else has had this problem. She also says that the Shared Solutions people weren't helpful.

Is this (blunt needles and therefore more difficult and more painful shots) something that happens with Copaxone?
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PostPosted: Fri Sep 21, 2007 4:34 pm    Post subject: (Abstract) Erythema nodosum & Copaxone in RRMS Reply with quote

From PubMed, September 21, 2007:

Quote:
Mult Scler. 2007 Aug;13(7):941-4

Erythema nodosum and glatiramer acetate treatment in relapsing-remitting multiple sclerosis

Thouvenot E, Hillaire-Buys D, Bos-Thompson MA, Rigau V, Durand L, Guillot B, Camu W.
Service de Neurologie, Hôpital Gui de Chauliac 80 avenue Augustin Fliche, 34295 Montpellier Cedex 5, France.

Glatiramer acetate (GA), a well tolerated immunomodulatory treatment for relapsing-remitting multiple sclerosis (RR-MS), consists of a 4-amino acid polymer that mimics the myelin basic protein (MBP). We report the first case of biopsy-proven erythema nodosum (EN) in a patient presenting RR-MS under GA treatment.

Comprehensive exams were negative in the search of the etiology of EN, which spontaneously resolved despite treatment continuation. GA treatment is known to generate reactive polyclonal antibodies that can cross-react with myelin epitopes, like MBP. These antibodies may also be implicated in allergenic reactions and auto-immune adverse events, such as anaphylactic shock, lymphadenopathy, livedo-like dermatitis, or lymphocytic infiltration. EN is an unspecific skin reaction occurring in several disorders and induced by many treatments. As EN can result from a polyclonal antibody response or type I hypersensitivity mechanisms, we hypothesize that GA treatment could be responsible for the occurrence of EN.

Multiple Sclerosis 2007; 13: 941-944. http://msj.sagepub.com.

PMID: 17881403
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PostPosted: Sat Oct 20, 2007 12:21 pm    Post subject: (Abstract) FOCUS study--fatigue & quality of life ... Reply with quote

From the ECTRIMS conference in Prague, October 11-14, 2007:

Quote:
FOCUS study – fatigue and quality of life in relapsing-remitting multiple sclerosis patients using glatiramer acetate improved at 6 and 12 months of treatment

P.J.H. Jongen, H. Carton, E.A.C.M. Sanders, P. Seeldrayers, S. Fredrikson, M. Andersson, D. Lehnick and the FOCUS Study Group


Introduction:

Fatigue is a common symptom in multiple sclerosis (MS). Metz et al. studied fatigue before and after 6 months of immunomodulatory treatment (IMT) in patients with relapsing-remitting (RR) MS. In 25% of glatiramer acetate treated patients fatigue decreased, as measured by the Fatigue Impact Scale (FIS), compared to 13% of INF-beta treated patients (Metz LM et al. 2004). To confirm this result and to study whether the positive effect of glatiramer acetate is sustained at 12 months, we performed the following study.

Methods:

197 RRMS patients starting glatiramer acetate treatment as IMT were studied: 135 Dutch, 42 Swedish and 20 Belgian patients. Outcomes measures were FIS, Leeds Quality of Life (QoL) Scale, Beck Depression Inventory (BDI), Guy’s Neurological Disability Scale (GNDS), and annualised relapse rate (ARR).

Measurements were performed at baseline, Month 6 and Month 12 (M12). Changes in scores were assessed for the complete group and for subgroups; subgroup analyses compared IMT-naïve patients (Group A) to patients with previous IMT (Group B) (t-tests). Data are given as mean and Standard Deviation (SD). Level of statistical significance 0.05, without adjustment for multiplicity.

Results:

Age 38.6 (9.6) years, % female patients 76.6, disease duration 4.3 (4.7) years, annualized relapse rate (ARR) previous 24 months 1.15 (0.62). For the total group (A+B) – strongly pronounced for group A, but not demonstrable for group B – mean scores for FIS total, FIS cognition, FIS physical and FIS social at M12 were lower than at baseline. The Leeds QoL score for the total group – again, strongly pronounced for group A, but not demonstrable for group B - was higher at M12 than at baseline. For BDI and GNDS scores no differences were found between baseline and M12. The ARR observed within 12 months of treatment tended to be lower in group A compared to group B.

Conclusion:

In RRMS patients treated with glatiramer acetate mean values for all FIS domains were lower at M12 than at baseline. Moreover, at M12 mean value for QoL was higher than at baseline. On subgroup analyses these results were also found for IMT-naïve patients, not for patients who had been treated with IMT before.

Our data indicate that glatiramer acetate may have a positive effect on fatigue in RR-MS, as suggested by Metz et al., and that the positive effect of glatiramer acetate on fatigue and QoL is sustained for at least 12 months.
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PostPosted: Wed Oct 24, 2007 5:58 pm    Post subject: (Abstract) Neurogenesis & neuroprotection in the CNS... Reply with quote

From PubMed, October 24, 2007:

Quote:
Mol Neurobiol. 2007 Dec;36(3):245-53

Neurogenesis and neuroprotection in the CNS - fundamental elements in the effect of glatiramer acetate on treatment of autoimmune neurological disorders

Arnon R, Aharoni R.
The Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel, ruth.arnon@weizmann.ac.il.

Multiple sclerosis (MS) is no longer considered to be simply an autoimmune disease. In addition to inflammation and demyelination, axonal injury and neuronal loss underlie the accumulation of disability and the disease progression.

Specific treatment strategies should thus aim to act within the central nervous system (CNS) by interfering with both neuroinflammation and neurodegeneration. Specific treatment strategies for autoimmune neurological disorders should aim to act within the CNS by interfering with both neuroinflammation and neurodegeneration.

The cumulative effect of glatiramer acetate (GA; Copaxone(R), Copolymer 1), an approved drug for the treatment of MS, reviewed herewith, draws a direct linkage between anti-inflammatory immunomodulation, neuroprotection, neurogenesis, and therapeutic activity in the CNS. GA treatment augmented the three processes characteristic of neurogenesis, namely, neuronal progenitor cell proliferation, migration, and differentiation. The newborn neurons manifested massive migration through exciting and dormant migratory pathways, into injury sites in brain regions, which do not normally undergo neurogenesis, and differentiated to mature neuronal phenotype, thus counteracting the neurodegenerative course of disease.

The plausible mechanism underlying this multifactorial effect is the induction of GA-reactive T cells in the periphery and their infiltration into the CNS, where they release immunomodulatory cytokines and neurotrophic factors in the injury site.

PMID: 17955199
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PostPosted: Thu Oct 25, 2007 10:10 am    Post subject: (Abstract) Managing injection site reactions w/Copaxone Reply with quote

From the ECTRIMS conference in Prague, October 11-14, 2007:

Quote:
Exploring interventions for management of injection site reactions with glatiramer acetate

H. Zwibel, H. Jolly, M. Oleen-Burkey, J. Conner, D. Denney on behalf of the Alcohol Wipes, Warm Compress, and Oral Antihistamine Study Groups

Background:

A common reason for discontinuing therapy early in the course of treatment for multiple sclerosis (MS) is the development of local injection site reactions (LISRs). Research directed toward reduction of LISRs can aid nurses who provide training and advice to patients regarding regular self-injection.

Objective:

Three studies were implemented to explore interventions for reducing LISRs prior to daily injections of glatiramer acetate (GA): 1) the elimination of alcohol wipes, 2) the use of warm compresses, and 3) the use of oral antihistamines.

Design/Methods:

Single cross-over designs with 50 patients were used to investigate the impact of 1) removing alcohol wipes from the injection site preparation and 2) using warm compresses on the injection sites for 5 minutes prior to self-injections of GA. A randomized placebo-controlled group design with 80 patients was used to investigate the impact of using an oral antihistamine 30 minutes prior to self-injections of GA. Patients used standardized daily diaries to record LISRs and were required to pass concordance testing before participating in the studies. The primary endpoint was total number of LISRs recorded at 5 minutes post-injection.

Results:

There was no statistically significant difference in LISRs when alcohol wipes were or were not used in the injection preparation for 30 days. However, patients recorded a significantly lower number of LISRs when warm compresses were applied to GA injection sites over 14 days compared to the usual site preparation (p = 0.002).

Compared to using placebo, patients who took an oral antihistamine prior to each self-injection of GA for 14 days did not record a statistically significant difference on the primary endpoints, but some post-hoc exploratory analyses did reveal some statistically significant differences between the treatment groups.

Conclusions:

At this time only warm compresses can be recommended for the management of LISRs associated with self-injections of GA.




http://tinyurl.com/35zz5o
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PostPosted: Sat Dec 08, 2007 6:42 pm    Post subject: Press release on early treatment w/Copaxone... Reply with quote

Press release from Teva Pharmaceuticals, December 3, 2007:

Quote:
Press Release

Early Treatment with COPAXONE® Demonstrated Robust Protection against Progression to Clinically Definite Multiple Sclerosis in the PreCISe Study


Efficacy Is Attained and the Study Is Stopped after Interim Analysis and Supports Filing of COPAXONE® For Patients with a First Clinical Event Suggestive of MS

Jerusalem, Israel, December 3, 2007 - Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) today announced the positive results from a pre planned interim analysis of the PreCISe trial in patients presenting with a first clinical event and MRI features suggestive of multiple sclerosis (MS). The results showed that treatment with COPAXONE® (glatiramer acetate injection) reduced the risk of developing clinically definite MS (CDMS) by 44 percent versus placebo, and prolonged the quartile time to disease conversion to 722 days versus 336 days (+386 days, +115%) in those patients receiving placebo (hazard ratio 0.56, p=0.0005). At the time of the interim analysis, the proportion of patients who had developed CDMS was reduced from 43 percent in the placebo group to only 25 percent in the COPAXONE® group. Based on these results, Teva plans to file a request for marketing authorization of COPAXONE® in Europe, the U.S. and Canada for the treatment of patients with a first clinical event suggestive of MS.

Professor Paul O'Connor, Neurology Division Chief at St. Michael's Hospital, Toronto, Canada and the chairman of the study's independent data monitoring committee (DMC), said, "We are deeply impressed by Teva's commitment to continue developing COPAXONE® for patients presenting with a first clinical event and MRI suggestive of MS. After analyzing the data from the PreCISe study at the interim analysis, the DMC recommended that the placebo arm of the trial be stopped, as COPAXONE® successfully met the efficacy endpoint of the study; all placebo patients will now be given the opportunity to receive active treatment with COPAXONE® for two years."

This study further demonstrated the beneficial effect of early treatment with COPAXONE® on disease activity and burden, also in its early stages, as measured by both short-term clinical and magnetic resonance imaging (MRI) disease outcomes. COPAXONE® is the only relapsing remitting MS (RRMS) treatment with data from a long-term, prospective, ongoing study which demonstrated that in those patients adhering to therapy, 92 percent still walk unassisted after a mean of 10 years of therapy and 18 years of disease duration.

Professor Giancarlo Comi, Department of Neurology, San Raffaele Scientific Institute, Milan, Italy, and principal investigator of the study said, "We are very pleased by the results of this trial. These data on COPAXONE® demonstrated the importance of treating patients early on to provide rapid, early control of progression to CDMS, and stand to improve therapy options for the treatment of patients with first clinical event and a high risk to develop MS."

Moshe Manor, Group Vice President - Global Innovative Resources of Teva Pharmaceutical Industries, Ltd., said: "The interim results of this study, which showed that early treatment with COPAXONE® delayed progression to CDMS, together with the unmatched long-term efficacy, tolerability and favorable safety profile supporting COPAXONE®, position it now also as the outstanding treatment option for patients with a first clinical event suggestive of MS and RRMS patients."


About the Study

The multi-national, multi-center, prospective, double-blind, randomized, Phase III PreCISe study was conducted in approximately 100 centers located in the U.S., Europe, Argentina, Israel, Nordic countries, Australia and New Zealand and included a total of 481 patients presenting with a single clinical episode and MRI suggestive of MS. Patients included are those who had a unifocal disease manifestation (i.e., clinical evidence of a single lesion). Patients received either COPAXONE® 20mg/day or placebo as a subcutaneous injection and continued treatment for up to 36 months, unless a second attack was experienced and they were diagnosed with clinically definite MS. Patients who converted to CDMS continued the trial on active treatment for an additional two years. The primary efficacy outcome was time to CDMS, based on a second clinical attack. The pre-planned interim analysis was performed on data accumulated from approximately 80 percent of the three-year placebo-controlled study exposure. Over the period up to the interim analysis, the proportion of patients developing CDMS was reduced from 43 percent in the placebo group to only 25 percent in the COPAXONE® group (p< 0.0001).

COPAXONE® was also very well tolerated in the PreCISe study, with only 13 percent overall dropouts during the up to three-year study period, similar to that observed in RRMS patients treated with COPAXONE®. All patients in the study participate in a follow-up study with COPAXONE® to asssess prospectively the impact of early versus delayed treatment with COPAXONE® on the long-term course of the disease for a total observation time of up to five years.

About COPAXONE®

Current data suggest COPAXONE® is a selective MHC (Major Histocompatability Complex) class II modulator. COPAXONE® is indicated for the reduction of the frequency of relapses in RRMS. COPAXONE® is very well tolerated, and the most common side effects of COPAXONE® are redness, pain, swelling, itching, or a lump or an indentation at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness.

COPAXONE® is now approved in 47 countries worldwide, including the United States, all European countries, Canada, Mexico, Australia, and Israel. In Europe, COPAXONE® is marketed by Teva Pharmaceutical Industries Ltd. and sanofi-aventis. In North America, COPAXONE® is marketed by Teva Neuroscience, Inc.

See additional important information at http://www.copaxone.com/pi/index.html or call 1-800-887-8100 for electronic releases.


http://www.tevapharm.com/pr/2007/pr_705.asp
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PostPosted: Wed Apr 30, 2008 3:08 pm    Post subject: Effect of Copaxone on axonal function Reply with quote

From the MS Foundation newsletter, April 30, 2008:

Quote:
EFFECT OF GLATIRAMER ACETATE ON AXONAL FUNCTION

Glatiramer acetate (GA) has several mechanisms of action with the potential of limiting axonal injury in the central nervous system (CNS). MR spectroscopy allows in vivo examination of axonal integrity by quantifying the neuronal marker N-acetylaspartate (NAA), often expressed as a ratio to creatine (Cr).

Researchers from Detroit Medical Center at Wayne State University School of Medicine showed that treatment with GA led to improvement in NAA/Cr over a two-year period. Researchers report the results of this ongoing study after four years with MR spectroscopy annually. Compared to baseline at year four, those receiving continuous GA therapy showed a 12.7% increase in NAA/Cr and in the multivoxel brain volume of interest (VOI) studied and by 9.6% in the normal-appearing white matter within the VOI. Three participants in the control group, who began therapy with GA during the course of the study, showed similar increases in NAA/Cr after the first year of therapy.

These data support the long-term effect of GA on maintaining axonal metabolic function and protection from sublethal injury as well as the feasibility of employing MR spectroscopy in long-term investigative studies in MS. MRS allows researchers to measure certain chemicals in the brain. NAA is a marker of how well the axons (nerve fibers) are working. While the precise role of NAA is unclear, Creatine (Cr) is used solely as a reference chemical. Studies have shown that NAA levels are frequently decreased on brain MRI in MS, even in areas of white matter that appear normal on standard MRI. So, there has been interest in using MRS to determine NAA/Cr ratios to look at the effect of different MS therapies on axonal function.
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PostPosted: Sat Jul 12, 2008 10:34 am    Post subject: Copaxone may be available in generic form Reply with quote

From The Economic Times, June 10, 2008:

Quote:




Natco inks agreement with Mylan for Copaxone
10 Jun, 2008, 2038 hrs IST, PTI


NEW DELHI: Home grown major Natco Pharma today said it has signed a licence and supply agreement with US-based Mylan for the global sale of generic version of Teva's patented 'Copaxone', a drug prescribed for multiple sclerosis.

"After an extensive review, we believe that no company is better positioned than Mylan to help us unlock the extraordinary value of this product in the United States and around the world," NATCO Chairman and Managing Director Chowadary V.Nannapaneni said in a statement.

Natco has signed the deal for its glatiramer acetate pre-filled syringes, a generic version of Teva's Copaxone, used in the treatment of multiple sclerosis.

The agreement grants Mylan exclusive distribution rights in the United States and all major markets in Europe, New Zealand, Australia, Japan and Canada and includes an option to expand into additional territories, Natco said.

Natco has successfully commercialised its glatiramer acetate product in India and Ukraine, it added.

About the agreement, Mylan said the company plans to work closely with all relevant regulatory agencies in the US and internationally and leverage Mylan's considerable global expertise in regulatory applications - to bring the therapeutic and economic benefits of this product to the widest possible patient-base.






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PostPosted: Wed Jul 23, 2008 8:50 am    Post subject: (Article) Double dose of Copaxone no better than 20mg dose Reply with quote

From Medical News Today, July 8, 2008:

Quote:
Multiple Sclerosis - Teva Provides Update On FORTE Trial

Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) announced top-line results from a Phase III study designed to assess the efficacy, safety and tolerability of glatiramer acetate (GA) 40mg as compared to the approved COPAXONE® 20mg in the treatment of relapsing-remitting multiple sclerosis (RRMS). The 40mg dose did not demonstrate increased efficacy in reducing the relapse rate; however, the higher dose maintained the favorable safety and tolerability profile of COPAXONE® 20mg.

Seventy-eight percent (78%) of COPAXONE® 20mg treated patients remained relapse-free throughout the study. Moreover, patients that completed one year of treatment with COPAXONE® 20mg experienced a very low annualized relapse rate of 0.27. This robust effect was also reflected in a remarkable reduction of inflammatory activity as measured by MRI.

"While the trial did not demonstrate an enhanced efficacy at the higher dose level, the study reaffirms that COPAXONE® 20mg, the leading multiple sclerosis therapy, remains the optimal treatment dose with unmatched long-term efficacy confirmed over 10 years," said Moshe Manor, Group Vice President - Global Innovative Resources. "Teva is committed to ongoing research in the field of multiple sclerosis and will continue to move forward towards providing additional treatment options to multiple sclerosis patients".

Teva will continue to analyze the study results to better understand the effect of GA 40mg on patients. The Company is also evaluating the use of GA for additional indications.

About the Study

A randomized, double-blind study, designed to assess the efficacy, safety and tolerability of 40mg glatiramer acetate, as compared to the currently approved COPAXONE® (glatiramer acetate) 20mg dose.

The study was conducted in 136 centers in North America, Argentina, Europe and Israel, and included 1,155 patients with RRMS. The trial's primary clinical outcome measure was rate of confirmed relapses.

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PostPosted: Tue Sep 16, 2008 4:20 pm    Post subject: (Abstract) Long-term effects of Copaxone in MS Reply with quote

From PubMed, September 16, 2008:

Quote:
[Long-term effects of glatiramer acetate in multiple sclerosis.]

[Article in French]


Brochet B.
Service de neurologie, pôle des neurosciences cliniques, clinique de la SEP, CHU Pellegrin, 33076 Bordeaux, France.

INTRODUCTION:


Multiple sclerosis is a chronic progressive neurological disorder. For this reason, the clinician needs to have access to treatments that are effective and well-tolerated over decades. However, in the absence of long-term controlled clinical trials, it is difficult to assess the long-term benefit provided by currently available immunomodulatory treatments.

The objective of this report is to review the strengths and limitations of available long-term data obtained in different phases of the randomized phase III clinical trial with glatiramer acetate collected over a 10-year period in particular.

METHODS:

Data were obtained from six published analyses of data from the phase III randomized clinical trial of glatiramer acetate performed at different times over a 10-year period. Initially patients were randomized to receive glatiramer acetate (n=125) or placebo (n=126) for 24 months under a double blind scheme, which was subsequently extended to up to 35 months. All patients were then proposed to continue glatiramer acetate treatment in an open-label prospective extension. Analyses of this extension study were performed at six and eight years after initial randomization. Finally, a pooled analysis was performed after a mean treatment duration of 10 years of all patients who had ever received glatiramer acetate during the study. Data were available for 68% of the original cohort at 10 years. At this stage, 108 patients (46.6%) had been continually treated with glatiramer acetate for a mean duration of 10 years.

RESULTS:


After one year of treatment, the annualized relapse rate decreased by around 50% from 1.18relapses/year before inclusion to 0.60relapses/year. Thereafter, relapse rates continued to decline progressively, reaching less than 0.2relapses/year from the ninth year of treatment onward. For 65% of patients, EDSS disability scores remained stable or improved over the entire treatment period, and 8% had reached a score of 6 on the EDSS scale (inability to walk unaided) after a mean continuous treatment duration of 10 years. With respect to safety, 23 patients (< 10%) needed to stop treatment due to an adverse event over the 10-year follow-up period. The most frequently encountered adverse events were local injection site reactions and systemic immediate postinjection reactions. No specific safety issue associated with long-term treatment was identified.

CONCLUSIONS:

The information collected from prospective long-term follow-up of patients treated with glatiramer acetate extending out to 10 years provides clear evidence for the long-term efficacy and adequate safety of this immunomodulatory treatment in the treatment of relapsing-remitting multiple sclerosis over a period of at least 10 years.

PMID: 18790510
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PostPosted: Tue Sep 30, 2008 8:40 am    Post subject: Smaller needles ahead for Copaxone users Reply with quote

Sorry I don't have anything "official-looking" to add to this post, but so far Shared Solutions hasn't issued anything in writing.

I did get the information from them by phone, though, and they are definitely changing over to smaller needles. They said some people have them already (as part of a trial they were doing), and others are getting them as they become available.

Their "availability" has a lot to do with whether your pharmacy has to use up a lot of the bigger needles. But people are asking their pharmacy for the smaller needles and getting them, apparently.

It's worth a try.

You can tell if you have the smaller needles because the rubber cap for the needle will be black instead of gray.

I'm really excited about this change. I hope it will mean easier shots for everybody.

EDITED TO ADD: I just took a closer look at my Copaxone syringes. I have the smaller needles already--didn't need to ask for them. Another way to tell if you have the new needles is by looking at the lot number. It will start with P instead of numbers.
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PostPosted: Sat Oct 04, 2008 1:22 pm    Post subject: (Abstract) 40mg Copaxone dose may be more effective Reply with quote

From WCTRIMS in Montreal, September 20, 2008:

Quote:
Presentation Category:
Disease Modifying Therapy



Results from a phase III, one-year, randomized, double-blind, parallel-group, dose-comparison study with glatiramer acetate in relapsing-remitting multiple sclerosis

G. Comi(1); J. A. Cohen2; M. Filippi3
1. Department of Neurology, University Vita-Salute and Scientific Institute San Raffaele, Milan, Italy.
2. Mellen MS Center, Cleveland, OH, USA.
3. Scientific Institute San Raffaele, Milan, Italy.



Results from a phase II study showed that 40mg dose of glatiramer acetate (GA) was possibly more effective than the currently approved 20mg dose in reducing MRI activity and clinical relapses.

To evaluate the safety, tolerability, and efficacy of GA 40mg compared to the 20mg dose.

Patients with definite MS (revised McDonald criteria), with at least one documented relapse in the 12 months prior to screening, or at least two documented relapses in the 24 months prior to screening, and EDSS score 0-5.5, were enrolled. Subjects were evaluated at screening, baseline, and at months 1, 2, 3, 6, 9, and 12. The primary endpoint was the rate of confirmed relapses observed during the study.

A total of 136 centers in 20 countries participated in the trial. Of the 1262 subjects screened, 1155 were randomized to GA 20mg (n=586) or 40mg (n=569). The groups were well-matched at baseline on demographic, clinical, and MRI characteristics. Annualized relapse rate (ARR) in the last year prior to study was 1.498. The primary efficacy endpoint was similar in both groups (relative risk=1.07, p=0.4859) with mean ARR of 0.33 for the 20 mg and 0.35 for the 40 mg group and 0.27 for those who completed one year treatment. Seventy-seven % of the patients remained relapse-free in both groups. Both groups showed a reduction in the mean number of gadolinium-enhancing and new T2 lesions over time with a trend for a faster reduction in the first trimester in the 40mg dose compared with 20mg dose. Both doses were well-tolerated with a safety profile similar to that observed in previous studies of 20mg GA.

In RRMS patients, both GA 40 mg and the currently approved 20mg doses were safe and well-tolerated, and were equally effective in reducing clinical relapses and MRI activity.







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PostPosted: Sat Oct 11, 2008 1:18 pm    Post subject: Neurology Now: Doctor's reply about Cochrane Review Reply with quote

I have been wondering why the Cochrane Review gave an unfavorable evaluation for Copaxone when most other research seems to support its use for MS. Neurology Now (September/October 2008, page 34) has a similar question, with a doctor's reply:

Quote:
MULTIPLE SCLEROSIS THERAPIES

[DEPARTMENT: ASK THE EXPERTS: YOUR QUESTIONS ANSWERED]

KANTOR, DANIEL

Daniel Kantor, M.D., is assistant professor of neurology and director of the Comprehensive Multiple Sclerosis Center at the University of Florida in Jacksonville, FL.

Q Why are glatiramer acetate therapies prescribed for multiple sclerosis (MS)? According to the Cochrane Collaboration, the evidence does not support use of these therapies.


A Glatiramer acetate (Copaxone) is one of four FDA-approved injectable medications for relapsing-remitting MS. An assortment of four amino acids (the building blocks of our bodies), glatiramer acetate was originally developed to give laboratory animals a disease similar to MS called experimental autoimmune encephalomyelitis (EAE). When glatiramer acetate failed to cause EAE in the mice, investigators gave it to mice that already had the disease, and it helped improve their symptoms. After much laboratory and animal research, clinical trials were started in human MS patients. There were some flaws in the statistical methods used in these trials, and so the Cochrane Collaboration-an international non-profit organization that reviews trials (Cochrane.org )-decided that these were not the best trials to support its use.

However, since the Cochrane Review was published, we have learned much more about glatiramer acetate, including how it works, the long-term benefits of staying on therapy, and even how it compares to beta interferons, the other class of injectable medications for MS. This also highlights how far we have come with MS medications; before 1993 there were no medicines for the condition, and now we have four injectable medications, two intravenous (IV) medicines, and dozens of ongoing clinical trials of IV and oral medicines. We have also come a long way in the methods we use to design clinical trials, which only give us a hint as to the full power of these medications.



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PostPosted: Mon Oct 13, 2008 6:37 pm    Post subject: (Abstract) Copaxone-associated ... lymphoma Reply with quote

From Archives of Neurology, vol. 65, no. 10, October 2008:

Quote:


Glatiramer Acetate–Associated, CD30+, Primary, Cutaneous, Anaplastic Large-Cell Lymphoma

Monica M. Madray, MD; John F. Greene Jr, MD; David F. Butler, MD


Arch Neurol. 2008;65(10):1378-1379.

Objective


To report the association of the development of a primary, cutaneous, anaplastic large-cell lymphoma after initiation of glatiramer acetate treatment of a patient with relapsing-remitting multiple sclerosis.

Design

Case report.

Setting

Dermatology outpatient clinic.

Patient

A 33-year-old white woman developed an erythematous nodule on her leg 4 months after starting treatment with glatiramer acetate. Biopsy showed primary, cutaneous, anaplastic large-cell lymphoma. Further evaluation showed no systemic involvement.

Intervention

Radiation therapy induced a complete remission.

Conclusions


Several T-cell–mediated skin conditions have been associated with the use of glatiramer acetate, such as pseudolymphoma, drug eruptions, and erythema nodosum. We report the association of a T-cell malignancy with the use of glatiramer acetate.




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PostPosted: Thu Oct 16, 2008 7:41 pm    Post subject: (Abstract) Copaxone after Novantrone improves MRI markers... Reply with quote

From PubMed, October 16, 2008:

Quote:
J Neurol. 2008 Oct 7

Glatiramer acetate after mitoxantrone induction improves MRI markers of lesion volume and permanent tissue injury in MS

Arnold DL, Campagnolo D, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Vollmer T.
NeuroRx Research, 3605 University Street, Suite 4, Montreal, Quebec Canada, H3A, 2B3, doug@neurorx.com.

BACKGROUND

Glatiramer acetate (GA) therapy following brief, low-dose induction with mitoxantrone was safe and more effective than GA alone in suppressing inflammatory disease activity, as determined by a significant reduction in gadolinium (Gd)- enhancing MRI lesions, in a 15-month, randomized, single-blind study of relapsing-remitting multiple sclerosis (RRMS) patients.

OBJECTIVE

To determine whether effects on MRI markers of disease burden and tissue damage support and extend data on the benefits of mitoxantrone induction therapy before initiation of long-term GA therapy.

DESIGN/METHODS

40 RRMS patients, aged 18 to 55 years, with 1-15 Gd-enhancing lesions on screening MRI and EDSS score 0-6.5 were randomized to receive GA (20 mg/d SC), starting 2 weeks after the last of 3 monthly mitoxantrone infusions (36 mg/m(2) total; n = 21), or to GA alone (20 mg/d SC; n = 19), for a total of 15 months. MRIs were obtained at baseline and months 6, 9, 12, and 15.

RESULTS

At baseline, mean (+/- SD) age was 37.2 +/- 9.7 years; disease duration, 3.5 +/- 4.8 years; EDSS score, 2.3 +/- 1.1; and number of Gd-enhancing lesions, 3.75 +/- 3.95. Reductions in Gd-enhancing lesions (RR = 0.30, 95 % CI, 0.11-0.86, p = 0.0147) and relapse activity favoring mitoxantrone- GA were accompanied by significant differences in changes in T2w lesion volume (p = 0.0139), T1w hypointense lesion volume (p = 0.0303), and proportion of Gd-enhancing lesions that evolved into black holes (p = 0.0023) compared with GA alone.

CONCLUSIONS

Long-term continuous GA after brief, low-dose mitoxantrone induction is safe and more effective than GA alone. A trend toward decreased clinical disease activity was accompanied by major effects on MRI measures of disease burden and severe tissue injury.

PMID: 18854910
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PostPosted: Sun Apr 26, 2009 10:26 am    Post subject: Health Canada approves Copaxone for CIS suggesting MS Reply with quote

From Doctor's Guide, April 24, 2009:

Quote:
Health Canada Approves Glatiramer Acetate for Clinically Isolated Syndrome Suggestive of MS"

NEW YORK -- April 17, 2009 -- Health Canada has approved an expanded indication for glatiramer acetate injection (Copaxone) to include the treatment of patients who have experienced a single demyelinating event, accompanied by abnormal magnetic resonance imaging (MRI) scans and are considered to be at risk of developing clinically definite multiple sclerosis (CDMS), after alternative diagnoses are excluded.

Administering glatiramer acetate to patients who have experienced a single demyelinating event has been shown to delay the onset of definite MS and reduce the number of active brain lesions and overall disease burden identified by MRI scans.

The approval is based on the multinational, multicentre, prospective, double-blind, randomised controlled, phase 3 (PreCISEe) study which included a total of 481 patients presenting with a single clinical episode and MRI scans suggestive of MS over a period of up to 3 years.

Patients included were those who had a unifocal disease manifestation. Patients were randomised to receive either glatiramer acetate injection 20mg/day or placebo as a subcutaneous injection and continued treatment for up to 3 years, unless a second exacerbation was experienced. Patients who experienced a second exacerbation continued the trial on active treatment for an additional 2 years.

he primary efficacy outcome was time to development of second exacerbation. A pre-planned interim analysis was performed on data accumulated from 81% of the 3-year placebo-controlled study exposure. Resutls demonstrated that in the 25th percentile of the patient population, the number of days to second exacerbation was more than doubled by treatment with glatiramer acetate from 336 days to 722 days (hazard ratio [HR] = 0.55; 95% confidence interval [CI], 0.40-0.77; [P = .0005), compared with placebo.


There was also a significant reduction in the number of new T2 lesions and in the volume of T2 lesions in the glatiramer acetate arm compared with the placebo arm, as measured by MRI scnas following 29 months of therapy.

Glatiramer acetate appears to be well tolerated with 84% of patients completing the 3-year study period.

SOURCE: CNW Group






The article can be seen here.
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PostPosted: Sun Sep 27, 2009 6:20 pm    Post subject: (Abstract) Copaxone w/minocycline in RRMS... Reply with quote

From PubMed, September 25, 2009:

Quote:
Mult Scler. 2009 Sep 23.

Glatiramer Acetate in Combination with Minocycline in Patients with Relapsing-Remitting Multiple Sclerosis: Results of a Canadian, Multicenter, Double-Blind, Placebo-Controlled Trial

Metz LM, Li D, Traboulsee A, Myles ML, Duquette P, Godin J, Constantin M, Yong VW.
University of Calgary.

Minocycline is proposed as an add-on therapy to improve the efficacy of glatiramer acetate in relapsing-remitting multiple sclerosis. The effect of minocycline plus glatiramer acetate was evaluated in this double-blind, placebo-controlled study by determining the total number of T1 gadolinium-enhanced lesions at months 8 and 9 in patients who were starting glatiramer acetate and had at least one T1 gadolinium-enhanced lesion on screening magnetic resonance imaging.

Forty-four participants were randomized to either minocycline 100 mg twice daily or matching placebo for 9 months as add-on therapy. They were assessed at screening and months 1, 3, 6, 8 and 9. Forty participants completed the study.

Compared with glatiramer acetate/placebo, glatiramer acetate/minocycline reduced the total number of T1 gadolinium-enhanced lesions by 63% (mean 1.47 versus 2.95; p = 0.08), the total number of new and enlarging T2 lesions by 65% (mean 1.84 versus 5.14; p = 0.06), and the total T2 disease burden (p = 0.10). A higher number of gadolinium-enhanced lesions were present in the glatiramer acetate/minocycline group at baseline; this was incorporated into the analysis of the primary endpoint but makes interpretation of the data more challenging.

The risk of relapse tended to be lower in the combination group (0.19 versus 0.41; p = NS).

Treatment was safe and well tolerated. We conclude that efficacy endpoints showed a consistent trend favoring combination treatment. As minocycline is a relatively safe oral therapy, further study of this combination is warranted in relapsing-remitting multiple sclerosis.

PMID: 19776092


The abstract can be seen here.
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PostPosted: Sun Nov 01, 2009 7:34 pm    Post subject: Cells from Copaxone-treated mice suppress EAE Reply with quote

From Experimental Neurology, through Science Direct Neurology, October 30, 2009:

Quote:
Article in Press, Accepted Manuscript

B Cells from Glatiramer Acetate-Treated Mice Suppress Experimental Autoimmune Encephalomyelitis

Mrinalini Kala, a, , Susan N. Rhodesa, Wen-Hua Piao1, a, Fu-Dong Shia, Denise I. Campagnoloa and Timothy L. Vollmer2, a

aBarrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 West Thomas, Road, Phoenix, AZ 85013, USA


Received 17 August 2009; revised 20 October 2009; accepted 23 October 2009. Available online 29 October 2009.


B Cells from Glatiramer Acetate-Treated Mice Suppress Experimental Autoimmune Encephalomyelitis

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) thought to be primarily mediated by T cells. However, emerging evidence supports an important role for B cells in the pathogenesis and inhibition of MS. Glatiramer acetate (GA), a Food and Drug Administration-approved drug for the treatment of MS, has a good safety profile. But GA’s mechanism of action in MS is still elusive.

In this study, we showed that B cells from GA-treated mice increased production of IL-10 and reduced expression of co-stimulatory molecules viz: CD80 and CD86. B cells from GA-treated mice also diminished proliferation of myelin oligodendrocyte glycoprotein (MOG35-55) specific T cells. Purified B cells transferred from GA-treated mice suppressed experimental autoimmune encephalomyelitis (EAE) in recipient mice compared with B cells transferred from mice treated with PBS or ovalbumin. The treatment effect of GA in EAE was abrogated in B cell-deficient mice. Transfer of B cells from GA-treated mice inhibited the proliferation of autoreactive T cells as well as the development of Th1 and Th17 cells but promoted IL-10 production in recipient mice. The number of peripheral CD11b+ macrophages in recipient mice also decreased after transfer of B cells from GA-treated mice; however, the number of dendritic cells and regulatory T cells remained unaltered. These results suggest that B cells are important to the protective effects of GA in EAE.


Corresponding author. Division of Neurology, Barrow Neurological Institute, 350 W. Thomas Road, Rm 420, Phoenix, AZ, 85013 USA. Tel.: +1 602 406 3086; fax: +1 602 406 8765.
1 Current address: Department of Clinical Laboratory, Ningxia People’s Hospital, Yinchuan, Ningxia Province, People’s Republic of China.
2 Current address: Department of Neurology, University of Colorado Health Sciences, 12631, East 17th Avenue, Aurora Colorado 80045, Mail Stop B 182.

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PostPosted: Thu Apr 15, 2010 5:58 pm    Post subject: (AAN abstract) Twice-weekly vs. daily Copaxone... Reply with quote

Presented at the annual AAN meeting in Toronto, April 10-17, 2010:

Quote:
Twice Weekly Versus Daily Glatiramer Acetate: Results of a Randomized, Rater-Blinded Prospective Clinical Trial Clinical and MRI Study in Relapsing-Remitting MS

Christina Caon, Jai Perumal, Alexandros Tselis, Wendy Ching, Fen Bao, Zahid Latif, Imad Zak, Omar Khan, Detroit, MI

OBJECTIVE:

To investigate in a small pilot study the safety, tolerability, and efficacy of glatiramer acetate (GA) 20 mg injected subcutaneously (SC) twice a week versus GA administered 20 mg SC daily in RRMS.

BACKGROUND:

The optimal dose of GA in RRMS remains unknown. We have previously shown that GA administered on alternate days appears to be as effective as daily GA. There is considerable interest in identifying the optimal dose of GA in RRMS.

DESIGN/METHODS:

We conducted a prospective, randomized, rater-blinded 2 year study to compare GA 20 mg SC twice a week to GA 20 mg SC daily. RRMS patients receiving GA 20 mg SC daily for at least one year were randomized to either continue in the same fashion or switch to GA 20 mg SC twice weekly. EDSS were recorded every 6 months and to confirm relapses, while brain MRI scans were done at baseline and month 24.

RESULTS:

48 RRMS were randomized into equal groups of GA 20 mg SC daily or GA 20 mg SC twice-weekly. Both groups were well-matched. After two years, the annualized relapse rate, mean EDSS, proportion of relapse-free patients, and the proportion of patients without disease progression were similar in the two groups. Brain MRI also did not demonstrate any significant changes in T2W or T1W lesion, or in the percentage brain volume change. However, the incidence of lipoatrophy, local injection site reactions, and immediate-post injection systemic reactions were significantly lower in the GA twice-weekly group.

CONCLUSIONS/RELEVANCE:

This study provides further evidence that GA administered less frequently than daily may be as efficacious and better tolerated than GA administered daily. This may have a significant impact in the clinical use of GA.

Larger, multi-center studies are warranted to confirm our findings and investigate the optimal dose of GA in RRMS.

Supported by: Wayne State University Neuroscience Program.
Category - MS and Related Diseases - Clinical Science

Tuesday, April 13, 2010 4:15 PM

Scientific Sessions: Multiple Sclerosis: Clinical Trials I (4:00 PM-5:15 PM)



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PostPosted: Sat Apr 24, 2010 7:18 pm    Post subject: (Abstract) Successful desensitization for treatment of MS Reply with quote

From PubMed, April 23, 2010:

Quote:


Ann Allergy Asthma Immunol
. 2010 Apr;104(4):321-5.

Glatiramer acetate: successful desensitization for treatment of multiple sclerosis

Bains SN, Hsieh FH, Rensel MR, Radojicic C, Katz HT, Inamdar SR, Lang DM.

Department of Allergy and Immunology, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.


BACKGROUND:

Glatiramer acetate is an immunomodulatory drug that is widely prescribed for the treatment of multiple sclerosis. It is frequently associated with local injection site reactions and generalized urticaria. It is also associated with immediate postinjection systemic reactions in approximately 10% of patients. To our knowledge, no desensitization protocols for glatiramer acetate have been published to date.

OBJECTIVES:

To evaluate the safety and efficacy of glatiramer acetate desensitization in a series of patients with multiple sclerosis.

METHODS:

Six patients with multiple sclerosis and glatiramer acetate-associated local or systemic reactions underwent a 4-hour outpatient desensitization procedure at Cleveland Clinic between 2003 and 2008. Beginning with 20 ng, we administered subcutaneous glatiramer acetate suspension in increasing dosages every 15 minutes. Patient outcomes were monitored by return clinic visit and telephone follow-up.

RESULTS:

No episodes of anaphylaxis or serious adverse reactions occurred during or immediately after desensitization. One patient suspended therapy after 14 months due to persistent local injection site reactions. All other patients successfully continued glatiramer acetate therapy.

CONCLUSION:

Glatiramer acetate offers significant benefit to patients with multiple sclerosis. Our experience suggests that patients who suspend its use owing to local or systemic reactions can be successfully and safely desensitized and can resume medication use. To our knowledge, this is the first report of successful desensitization to glatiramer acetate in patients with multiple sclerosis.

PMID: 20408342


The abstract can be seen here.
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PostPosted: Thu Jun 10, 2010 6:30 pm    Post subject: Teva: Positive results for new Copaxone formulation Reply with quote

From Medical News Today, June 8, 2010:

Quote:
Teva Announces Positive Results From A Study Assessing A New Formulation Of Copaxone(R)


Teva Pharmaceutical Industries Ltd. announced positive results from a study assessing a new lower-volume injection of Copaxone® (glatiramer acetate) containing the currently approved dose in half the injection volume.

The SONG study ('Study of New Glatiramer Acetate Formulation') explored the safety and tolerability of a 20mg/0.5mL injection of Copaxone® versus the current formulation of 20 mg/1.0mL.

These findings were presented at the 24th Annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC) in San Antonio, Texas.

"Copaxone® has proven long-term efficacy, safety and tolerability with more than one million patient years of treatment," said Dr. Ronald Murray, FAAN, a lead study investigator and Director of the MS Clinic of Colorado. "We are encouraged by these data as they suggest that a 0.5mL dose of glatiramer acetate may enhance patients' experience with the most frequently prescribed MS therapy."

The SONG study enrolled 148 relapsing-remitting MS patients (RRMS) at 21 sites in the United States. Data demonstrated that both the 1.0mL and 0.5mL products were safe and well tolerated. Patients receiving the lower-volume injection reported significantly less pain immediately following and five minutes after administration (p<0.0001). Although the presence of injection site reactions (swelling, redness, itching, lumps) was not high for either group, patients reported fewer and less severe reactions within five minutes (p<0.0001) and 24 hours (p<0.0001) post-administration with the 20mg/0.5mL product. No serious adverse events were reported in the study.

"Copaxone® is the global market leading RRMS treatment, and Teva is continuously pursuing research focused on further enhancing the patient treatment experience with the product," said Moshe Manor, Teva's Group Vice President, Global Branded Products. "Our investment in research has already translated to increased benefits for Copaxone® patients, including an expanded indication to treat early-stage MS-like symptoms in patients at risk of progression to an MS diagnosis, as well as device improvements such as a thinner needle to reduce injection discomfort and an auto inject device to better facilitate treatment delivery."

About the Study


Patients (N=148) enrolled in an open-label randomized two-arm single crossover study. Half of the patients (n=76) were randomized to inject 20mg/1.0mL daily for the first 14 day period (Period 1); the other half of the patients (n=72) injected 20mg/0.5mL daily during Period 1. During the second 14 day period (Period 2), the groups switched their injection volume formulation. Patients completed a daily diary reporting pain occurring immediately and at 5 minutes post injection, as well as the presence and severity of injection site reactions within 5 minutes and 24 hours of injection. Safety, tolerability, clinical and laboratory assessments occurred during the course of the study. Adverse events were reported by 12.5 percent of patients when injecting 20mg/1.0mL and by 18.1 percent of patients when injecting 20mg/0.5mL.

Overall, the AE profile of Copaxone in patients treated with either formulation was consistent with Copaxone's observed safety profile in placebo-controlled pivotal trials and post-marketing experience.

...

Source
Teva Pharmaceutical Industries Ltd.
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PostPosted: Fri Jul 16, 2010 11:49 am    Post subject: Reply with quote

Neura.net's current issue of MS Scan (issue 26, 2010) has an article, "Effects of antihistamines on injection-site reactions," with some good information about ways to cut down on site reactions while taking Copaxone. The article can be seen here.
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PostPosted: Thu Aug 26, 2010 2:41 pm    Post subject: (Abstract) Treatment switching criteria... Reply with quote

From Multiple Sclerosis, August 24, 2010:

Quote:
A method for evaluating treatment switching criteria in multiple sclerosis

Brian C Healy bchealy@partners.org
Partners Multiple Sclerosis Center, Department of Neurology, Brigham & Women’s Hospital/Biostatistics Center, Massachusetts General Hospital, Boston MA, USA

Bonnie I Glanz
Partners Multiple Sclerosis Center, Department of Neurology, Brigham & Women’s Hospital, Boston MA, USA

James Stankiewicz
Partners Multiple Sclerosis Center, Department of Neurology, Brigham & Women’s Hospital, Boston MA, USA

Guy Buckle
Partners Multiple Sclerosis Center, Department of Neurology, Brigham & Women’s Hospital, Boston MA, USA

Howard Weiner
Partners Multiple Sclerosis Center, Department of Neurology, Brigham & Women’s Hospital, Boston MA, USA

Tanuja Chitnis
Partners Multiple Sclerosis Center, Department of Neurology, Brigham & Women’s Hospital, Boston MA, USA

Background and Objective:

We investigated a method to evaluate a treatment switching approach, namely treatment change after one multiple sclerosis (MS) relapse.

Methods:

Patients who experienced a relapse while on a first-line disease-modifying therapy, glatiramer acetate, were identified. Based on their subsequent course, patients were divided into two groups: those who changed treatment and those who did not. Patients were allowed to change to any other treatment.

Subsequent annualized relapse rate and time to next relapse were compared in the two groups. Since patients were not randomized to treatment group, negative binomial and Cox regression models were used to control for several potential clinical confounders, including relapse severity, relapse duration, age, disease duration and presence of previous/combination therapy. In addition, an inverse probability of treatment weighting model was used to control for confounding. Several secondary analyses investigated patient subgroups.

Results:

Statistical modeling showed that there was no significant difference between groups in terms of relapse rate (rate ratio; 95% CI = 0.68; 0.35, 1.31) and time to next relapse (hazard ratio; 95% CI = 0.61; 0.30, 1.25). All secondary analyses confirmed these results. In addition, no significant difference in time to sustained progression on the Expanded Disability Status Scale was observed (p > 0.05). Our approach allowed investigation of the choice to change treatment after a relapse.

Conclusions:

Our results showed that a single relapse may not be sufficient to indicate treatment failure. Although clinical confounders were addressed in our modeling, unmeasured confounders, particularly the presence of magnetic resonance imaging activity, may have biased our conclusion.


The abstract can be seen here.
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PostPosted: Sun Dec 12, 2010 6:26 pm    Post subject: Lipoatrophy in Canadian MS patients on Copaxone Reply with quote

From the International Journal of MS Care (Winter 2010), "Lipoatrophy in Canadian Multiple Sclerosis Patients Receiving Glatiramer Acetate: Report of a Postmarketing Observational Study."

The article can be seen here.

The study was funded by Teva Neuroscience. It shows an occurrence of lipoatrophy in 85% of the patients in the study. Over half of the patients had been on Copaxone for 5 years or longer.
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PostPosted: Tue Dec 28, 2010 6:57 pm    Post subject: Copaxone in first MS attack Reply with quote

Journal Watch has named this one of the top 10 neurology stories for 2010.

Quote:
Glatiramer Acetate in First MS Attack

The PreCISe trial showed, unsurprisingly, that glatiramer acetate can delay a second clinical attack and decrease silent brain-lesion development in patients with a clinical isolated syndrome.

In this international, randomized, double-blind, manufacturer-funded, phase III study (the PreCISe trial), researchers compared glatiramer acetate (GA) with placebo to treat patients with a clinically isolated syndrome, who are at high risk for multiple sclerosis (MS). Researchers randomized patients aged 15 to 45 to daily, subcutaneous GA (N=243) or placebo (N=238) injections, within 90 days of a unifocal clinically isolated syndrome (such as monocular optic neuritis or incomplete transverse myelitis). All had at least two brain lesions 6 mm in diameter. The 3-year trial terminated early, at a preplanned interim analysis at 2.3 years.

Among the quarter of participants who had a second attack, the primary outcome — time to second clinical attack — was delayed significantly with GA compared with placebo, by 386 days, a 45% reduction in relative risk. Relapses occurred in 42.9% of the placebo group and in 24.7% of the GA group, a significant difference. The number of new T2 brain MRI lesions was significantly smaller with GA treatment (by 58%; 0.7 vs. 1.8), as was T2 lesion volume. Brain atrophy rates did not differ between treatment groups.

In post hoc analyses, GA response was better in women than in men; in those younger than 30 than in older patients; in those with 1 enhancing lesion or <9 T2 lesions on baseline MRI than in those without these characteristics; and when steroids were not used for the initial attack compared with when they were. Early study termination occurred in 37 (15.2%) of the GA group and 21 (8.8%) of the placebo group, but only 14 (5.8%) and 4 (1.7%) patients, respectively, dropped out because of adverse events. The authors conclude that GA is a safe, effective treatment for patients with a clinically isolated syndrome.

Comment: These results show a clear benefit, over 2 years, in using GA (vs. placebo) to treat patients with a clinically isolated syndrome. This finding is no surprise, because GA is an established therapy for relapsing MS. Notably, the study included only patients with a unifocal first attack, which carries a milder (better) prognosis than a multifocal first attack. That women had a better response is surprising in light of the GA primary progressive trial, wherein men showed a better response (Ann Neurol 2007; 61:14). I do not put a lot of weight on these limited post hoc analyses. Although the lack of effect on brain atrophy is disappointing, the authors suggest several explanations. Most important, many PreCISe trial patients continue to be followed in a long-term extension study.

This study provides a sound rationale to consider GA, along with interferon beta, as a treatment option for patients with a clinically isolated syndrome.

— Patricia K. Coyle, MD

Dr. Coyle is Professor and Acting Chair, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York. Stony Brook was a center that participated in the PreCISe trial, although Dr. Coyle was not principal investigator.

Published in Journal Watch Neurology January 12, 2010

Citation(s):

Comi G et al. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): A randomised, double-blind, placebo-controlled trial. Lancet 2009 Oct 31; 374:1503.



The article can be seen here.
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PostPosted: Mon Feb 28, 2011 1:43 pm    Post subject: Shared Solutions notice about alcohol prep pads recall Reply with quote

Triad alcohol prep pads, normally included in shipments of Copaxone, have been recalled, and the Shared Solutions Website has a notice about this recall:

http://www.sharedsolutions.com/Information/TakingCOPAXONE/TriadRecall.aspx
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PostPosted: Fri Jun 24, 2011 6:14 pm    Post subject: End enrollment in phase 3 trial for 3x-weekly Copaxone Reply with quote

From Medical News Today, June 3, 2011:

Quote:
Teva Completes Enrollment In Phase III Multiple Sclerosis Trial Evaluating Glatiramer Acetate Three Times Weekly

Teva Pharmaceutical Industries Ltd. today announced completion of patient enrollment for the GALA (Glatiramer Acetate Low-frequency Administration) trial. This international Phase III trial in patients with relapsing-remitting multiple sclerosis (RRMS), is designed to examine the efficacy, safety and tolerability of 40mg COPAXONE® (glatiramer acetate injection) administered three times a week compared to placebo. The primary endpoint of the trial is the total number of confirmed relapses during a 12-month placebo-controlled phase, which will be followed by an open-label extension phase.

Patient enrollment was completed in May 2011, recruiting over 1,400 patients at 180 sites in the United States, Europe, Central Eastern Europe and Israel. Results from the trial are expected in the second quarter of 2012.

"The GALA trial demonstrates Teva's commitment to the continued research and development of COPAXONE®, the global-leading RRMS therapy with 20 years of robust efficacy and safety data," said Professor Yitzhak Peterburg, Teva's Group Vice President, Global Branded Products. "With glatiramer acetate 40mg three times a week, we hope to further enhance the patient experience over the long-term."

The GALA study investigates glatiramer acetate 40mg administered three times a week in comparison to placebo. This dose (glatiramer acetate 40mg) is a higher strength than the currently marketed 20mg of COPAXONE® injected daily.

COPAXONE® is currently approved in over 50 countries worldwide and is indicated for the treatment of RRMS and for patients presenting with clinically isolated syndrome (CIS). It is the worldwide market-leading RRMS treatment with a global market share of 31%.

...

Source:
Teva Pharmaceutical Industries Ltd.


The article can be seen in its entirety here.
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PostPosted: Sun Mar 25, 2012 8:15 am    Post subject: FDA "Cease & Desist" letter about Copaxone Reply with quote

Apparently the US FDA has sent a warning letter to Teva Pharmaceuticals ordering them to "cease and desist" issuing misleading promotional material about the benefits of Copaxone. The letter, dated March 12, 2012, can be seen here.
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PostPosted: Wed Oct 31, 2012 3:52 pm    Post subject: New Copaxone dosing Reply with quote

If this dosage is adopted, a Copaxone user would be getting a bit less of the drug--140mg/mL/week vs. 120 mg/mL/week.

From the MS Foundation Newsletter, MSFYi, October 31, 2012:

Quote:
New Dosing for Copaxone

Data from a phase III trial support the efficacy of a new dosing regimen for Copaxone® (glatiramer acetate) for patients with relapsing-remitting MS.

Teva Pharmaceutical Industries released data from the Glatiramer Acetate Low-Frequency Administration (GALA) study, which was designed to evaluate the efficacy, safety, and tolerability of 40 mg/mL of glatiramer acetate three times weekly instead of the 20-mg/mL daily subcutaneous injection that has been the recommended dose for almost two decades.

In the GALA study, a one-year, randomized, double-blind, placebo-controlled trial, glatiramer acetate 40 mg/mL injected three times weekly significantly reduced annualized relapse rates by 34.4 percent versus placebo. The cumulative number of new and enlarging T2 lesions was significantly reduced by the same percentage.

In addition, a significant 44.8 percent reduction in the cumulative number of gadolinium-enhancing lesions was observed in people treated with the investigational dosing regimen. At 12 months, there was no significant difference in percentage change of brain volume between the glatiramer acetate-treated patients and those receiving placebo. Discontinuation rates among the two cohorts were comparable.

Glatiramer acetate in a dose of 40 mg/mL also showed a favorable safety and tolerability profile. The overall frequency of adverse events was comparable to that of the placebo group. The most common reported adverse events were injection-site reactions, headaches, and nasopharyngitis.

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PostPosted: Sun Sep 08, 2013 11:17 pm    Post subject: Copaxone 3 times weekly may or may not happen Reply with quote

From www.bloomberg.com, July 29, 2013:

Quote:
Teva Plan to Safeguard $4 Billion Drug Endangered by Ruling

By David Wainer

Teva Pharmaceutical Industries Ltd. (TEVA)’s plan to switch patients to a longer-acting version of its Copaxone treatment suffered a setback as a U.S. court ruling gave the $4 billion drug less than a year of patent protection.

Teva wants to move as many as half of the multiple-sclerosis patients taking daily Copaxone injections to a three-times-weekly version of the medicine. The U.S. Court of Appeals decision to invalidate a 2015 patent may allow generic competitors such as Cambridge, Massachusetts-based Momenta Pharmaceuticals Inc. (MNTA) to lure away patients with cheaper copies as early as next year, said Marc Goodman, an analyst at UBS AG.

“This not only moves up the potential generic Copaxone launch into 2014 but it also doesn’t give Teva much time to convert patients,” said Goodman, who is based in New York. The analyst said he changed his earnings forecast to reflect a generic competitor by 2014 and a 15 percent patient conversion instead of a previously forecast 30 percent.

Teva, based in Petach Tikva, Israel, markets a 20-milligram Copaxone injection, which generates more than five times the revenue of its second-best-selling branded drug, Treanda.

A longer-acting, 40-milligram dose of Copaxone was effective in lowering relapse rates in MS patients compared with a placebo in a late-stage trial last year.

Extra Year

Because Teva expects the U.S. Food and Drug Administration to approve the long-acting version by early 2014, the extra year without generic competition would be key to moving its patients to the higher dosage.

“Teva wanted to switch a significant portion of its prescriptions to the 40-milligram dose but that will be de facto impossible if the market goes generic in May 2014,” said Ori Hershkovitz, a partner at Sphera Funds Management Ltd., a Tel Aviv-based health-care hedge fund.

...

Switching Patients

Teva expects 30 percent to 35 percent of its patients to switch, Jon Congleton, senior vice president at Teva’s Global Medicines Group, said in a first-quarter earnings conference call. Market research done by Teva showed as many as half of all Copaxone patients would transition to fewer weekly injections, Congleton said. The newer formulation would have patent protection through 2030.
Generic-drug makers still face hurdles in getting their products to the market next year. Teva can seek a review before the U.S. Supreme Court and the company said it will appeal the decision. The FDA would need to approve copies of the drug and Teva says that the regulator should require lengthy clinical trials not typical for generic medicines because Copaxone is a complex molecule.
“Since the generics did not receive FDA approval, nor is there any indication as to when, if at all, such approval would be received, it is too early to assess if there will be any impact on Copaxone, and specifically on our launch of Copaxone 40-milligram 3-times-a-week,” Teva said in an e-mailed statement.

Momenta’s application with the FDA for a generic has been under review for five years and the regulatory pathway “remains murky,” said David Steinberg, a San Francisco-based analyst at Deutsche Bank AG. There is a real possibility that a generic to Copaxone may not emerge for a number of years, said Steinberg, who has a buy recommendation on Teva.

A generic approval in 2014 is increasingly possible as the FDA demonstrates more willingness to approve complex drugs, said Ronny Gal, an analyst at Sanford C. Bernstein & Co. Gal estimated the chances of a generic entrant next year at 50 percent.

________________

To contact the reporter on this story: David Wainer in Tel Aviv at dwainer3@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net


The story can be seen in its entirety here.
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