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MS TREATMENTS: FINGOLIMOD/GILENYA/FTY720

 
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PostPosted: Sat Mar 02, 2013 2:39 pm    Post subject: MS TREATMENTS: FINGOLIMOD/GILENYA/FTY720 Reply with quote

Fingolimod (Gilenya) is given orally in daily doses of 0.5mg and does not need to be refrigerated.

Last edited by agate on Mon Jul 22, 2013 4:48 pm; edited 1 time in total
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PostPosted: Sat Mar 02, 2013 2:59 pm    Post subject: Fingolimod (Gilenya) approved--1st oral MS drug [9/23/10] Reply with quote

This is an FDA news release, September 22, 2010:

Quote:
FDA NEWS RELEASE

For Immediate Release: Sept. 22, 2010
Media Inquiries: Sandy Walsh, 301-796-4669, sandy.walsh@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA approves first oral drug to reduce MS relapses

The U.S. Food and Drug Administration has approved Gilenya capsules (fingolimod) to reduce relapses and delay disability progression in patients with relapsing forms of multiple sclerosis (MS).

“Gilenya is the first oral drug that can slow the progression of disability and reduce the frequency and severity of symptoms in MS, offering patients an alternative to currently available injectable therapies,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research.

Gilenya is the first in a new class of drugs that block some blood cells in lymph nodes, reducing their migration to the brain and spinal cord, which may help with reducing the severity of MS.

MS is a chronic, often disabling, disease that affects the central nervous system—the brain, spinal cord, and optic nerves. According to the National Multiple Sclerosis Society, there are about 400,000 people in the United States and 2.1 million people worldwide with MS.

The progress, severity, and specific symptoms of MS are unpredictable and vary from one person to another. Symptoms can be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.

Patients using Gilenya should be monitored for a decrease in heart rate upon starting the drug. Gilenya may also increase the risk of infections. Cases of serious eye problems (macular edema) have occurred in patients taking the drug and an ophthalmologic evaluation is recommended.

The most frequent adverse reactions reported by patients taking Gilenya in clinical trials include headache, influenza, diarrhea, back pain, elevation of certain liver enzymes and cough.

The drug will be available in 0.5 milligram capsules. Gilenya is made by Novartis, Basel, Switzerland.

For more information:

National Institute of Neurological Disorders and Stroke: Multiple Sclerosis Information


Another thread provides a study comparing fingolimod and Avonex, published in the New England Journal of Medicine in February.
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PostPosted: Thu Mar 14, 2013 1:39 pm    Post subject: (Abst.) Fingolimod impact on MRI outcomes [10/12] Reply with quote

From Archives of Neurology, October 2012:

Quote:

Impact of Fingolimod Therapy on Magnetic Resonance Imaging Outcomes in Patients With Multiple Sclerosis

Ernst-Wilhelm Radue, MD; Paul O’Connor, MD; Chris H. Polman, MD; Reinhard Hohlfeld, MD; Peter Calabresi, MD; Krystof Selmaj, MD; Nicole Mueller-Lenke, MD; Catherine Agoropoulou, PhD; Frederick Holdbrook, PhD; Ana de Vera, MD; Lixin Zhang-Auberson, MD; Gordon Francis, MD; Pascale Burtin, MD; Ludwig Kappos, MD; for the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) Study Group


Objective

To assess the impact of fingolimod (FTY720) therapy on magnetic resonance imaging measures of inflammatory activity and tissue damage in patients participating in a 2-year, placebo-controlled, phase 3 study.

Design

Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change.

Findings were compared across subgroups by treatment and baseline characteristics.

Setting

Worldwide, multicenter clinical trial.

Patients

Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N = 1272).

Main Outcome Measures

We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume.

Results

Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P < .001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P < .05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P < .05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability.

Conclusion

These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution.

Trial Registration clinicaltrials.gov

Identifier: NCT00289978




The abstract can be seen here.
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PostPosted: Thu Mar 14, 2013 1:43 pm    Post subject: (Abst.) Early tolerability, safety of fingolimod [10/9/12] Reply with quote

From PubMed, October 9, 2012:


J Neurol Sci. 2012 Oct 3.

Early tolerability and safety of fingolimod in clinical practice

Ontaneda D, Hara-Cleaver C, Rudick RA, Cohen JA, Bermel RA.

Mellen Center, Department of Neurology, Cleveland Clinic, Cleveland, OH, USA. Electronic address: ontaned@ccf.org.

BACKGROUND:

Fingolimod is approved by the U.S. Food and Drug Administration to reduce relapses and disability progression in relapsing forms of MS. Several screening studies and a first-dose observation (FDO) period are recommended due to adverse effects observed in clinical trials.

OBJECTIVE:

The objective of this study is to describe the early experience with fingolimod, including startup, tolerability and safety in a large academic multiple sclerosis (MS) center.

METHODS:

Patients prescribed fingolimod from September 2010 to July 2011 were identified through electronic medical records. Demographics, MS disease history, pre-treatment screening studies, FDO experience during shared medical visits and three month follow-up data were analyzed.

RESULTS:

Three hundred ninety-one patients were prescribed fingolimod of whom 317 started the medication and were included in the analysis. Fingolimod was most frequently used in relapsing remitting MS (n=256, 80.8%) and was prescribed as a first-line agent in 11 cases (3.5%). FDO was uneventful in 308 patients (96.8%). Adverse events during FDO were self limited and included symptomatic bradycardia (n=3), chest tightness (n=2) and hypertension (n=1).

Fingolimod was discontinued in 30 patients (9.5%) at three months. Adverse effects leading to discontinuation by more than one patient included headache (n=4), macular edema (n=3), nausea (n=3) and hypertension (n=2).

CONCLUSIONS:

Fingolimod was well tolerated during FDO and adverse events were self limited. The shared medical visit is an appropriate setting for FDO. Adverse effects were similar to those described in clinical trials but the discontinuation rate was higher.


PMID:23040960[/quote]


The abstract can be seen here.
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PostPosted: Thu Mar 14, 2013 5:56 pm    Post subject: FTY720 first oral drug for MS? [April 2008] Reply with quote

Posted in April 2008:

From HealthDayNews, April 15, 2008:

Quote:
Pill Reduces Relapses in MS Patients

First oral drug could benefit many with the autoimmune disease, researchers say

By Steven Reinberg, HealthDay Reporter




TUESDAY, April 15 (HealthDay News) -- The first pill designed to reduce the number of attacks in people with multiple sclerosis appears to be effective in early tests, Italian researchers report.

The pill was effective in preventing relapses in more than 60 percent of patients who took the pill for three years, according to research that was expected to be presented April 15 the American Academy of Neurology annual meeting, in Chicago.

"All of the current treatments for MS must be injected, so having a pill you can swallow with a glass of water would be a welcome improvement for many people," lead researcher Dr. Giancarlo Comi, from Vita-Salute San Raffaele University in Milan, said in a prepared statement.

In the study, Comi's team treated 281 people with relapsing MS with FTY720 (fingolimod) or a placebo. After six months, two-thirds of the patients who received FTY720 had more than 50 percent fewer relapses, compared with those receiving placebo.

During the three years of the trial, more than 67 percent of the 173 people receiving FTY720 were free of relapses. In addition, 89 percent of the patients were free of disease activity and 75 percent did not develop new lesions or see their lesions enlarge. This was confirmed by MRI scans, the researchers stated.

"The first-line treatments for MS, beta interferon and glatiramer acetate, reduce the relapse rate by only about 30 percent, so this is a significant development for people with MS," Comi said in a statement.

The most commonly reported side effects of FTY720 were headache, flu and cold symptoms.

The drug works by binding to receptors on immune cells, isolating them in the lymph nodes, thereby reducing their ability to cause the damage associated with MS symptoms.

The study was paid for by Novartis Pharma AG, maker of FTY720.

One expert thinks this preliminary data is encouraging, but a lot more needs to be done to prove the drug's effectiveness.

"This is a new drug that has a very strong scientific rationale why it could work," said Dr. John Richert, executive vice president of the National Multiple Sclerosis Society. "Certainly, everything we've seen so far continues to keep us optimistic."

Richert noted that over three years, 77 patients receiving the drug dropped out of the study. "You're left wondering if a more severe adverse event led to the dropouts," he said.

The six-month data where the drug was tested against placebo looks promising, Richert said. "If this turns out to be a safe oral drug that has substantial benefit, that will be very important for many people with MS," he added.



SOURCES: John Richert, M.D., executive vice president, National Multiple Sclerosis Society, New York City; April 15, 2008, presentation, American Academy of Neurology annual meeting, Chicago


____________________________________________________
[posted April 16, 2008]

A WebMD article on this is available here.

__________________________________________________

[posted April 30, 2008]

From Medscape Medical News, April 25, 2008 (charts omitted):

Quote:

Fingolimod 3-Year Results Show Continued Low Relapse and Disease Activity in MS

Susan Jeffrey


April 25, 2008 (Chicago) — Results from the 3-year extension of an earlier randomized trial of FTY720, or fingolimod (Novartis), a still-investigational oral treatment in patients with relapsing-remitting multiple sclerosis (RRMS), show continued low rates of relapse and disease activity on magnetic resonance imaging (MRI), researchers report.

Results of the extension study, funded by Novartis Pharma AG, were presented here at the American Academy of Neurology 60th Annual Meeting.


"In conclusion, here we have a drug that is an oral drug, and this is a very important point to underline" for patients, Giancarlo Comi, MD, from Vita-Salute San Raffaele University, in Milan, Italy, told a press conference here. "The drug, based on the data that we have, seems to be active even for the extended 3-year period tested in this type of clinical trial, and it seems that the safety profile, at least as far as we know today, is not presenting any major problems."

An Oral Alternative

Currently approved treatments for MS are the immune-modulating agents beta interferon and glatiramer acetate, which reduce relapse rates by about 30%, the authors note. However, both types of drugs are given either intramuscularly or subcutaneously, and interferons are associated with systemic reactions in some 60% of patients, with implications for adherence to treatment.

Fingolimod is a still-investigational drug that, given orally, acts as a superagonist to sphingosine-1-phosphate (S1P) receptors on the surface of thymocytes and lymphocytes, causing them to be sequestered in secondary lymph organs. This reduces the overall number of circulating lymphocytes available to mount an autoimmune reaction to the myelin sheath surrounding axons in MS. The phase 2 study was a double-blind, placebo-controlled proof-of-concept study that randomized 281 patients with relapsing MS to 1 of 3 treatment groups — 1.25-mg oral fingolimod, 5.0-mg oral fingolimod, or placebo — for 6 months (the core study). The primary end point was the total cumulative number of gadolinium-enhancing lesions on 6 postbaseline MRI scans. Other MRI parameters and clinical parameters were also evaluated. Of 281 randomized patients, 255 completed the 6-month core study. The most common reasons for premature discontinuation were adverse events and withdrawal of consent, the authors note. In their report of the primary results, published in 2006 in the New England Journal of Medicine, the authors showed that the median number of enhancing lesions on MRI — indicative of active disease — was significantly reduced with fingolimod treatment compared with placebo. Although the study was not powered to detect a treatment effect on clinical relapse-related end points, the authors pointed out that there were significant improvements in the annualized relapse rate with both fingolimod doses (reduced by 53% in the 5.0-mg group and 55% in the 1.25-mg group) compared with placebo (Kappos L et al. N Engl J Med. 2006;355:1124-1140). They then carried out a long-term extension study, where patients who had received placebo in the core study were randomized again to 1 of the 2 fingolimod doses. Of the 255 patients who completed the core study, 250 entered the extension. Investigators and patients remained blinded during this phase to their original treatment assignment.

Results of the first 6 months of that extension study with oral fingolimod in patients with RRMS, published in the original report, continued to show low levels of disease activity on MRI as well as low relapse rates in patients who received the drug continuously through 12 months. The group of patients who had been receiving placebo during in the core study and were switched to active drug in the extension showed marked reduction in disease activity on MRI and clinical relapses after 6 months on fingolimod compared with the 6 months on placebo.

At the meeting here, Dr. Comi and colleagues reported on the results of the analysis at 36 months (30 months of the extension to the original 6-month core trial). A total of 173 of the 250 patients who entered the extension study completed month 36.

Between month 18 and month 24, all patients who had been on the 5-mg dose were converted to 1.25 mg, since both doses were equally effective, but the lower dose was seen to be better tolerated. At the month-36 analysis, patients originally on the 5-mg dose had been receiving 1.25 mg for at least 12 months.

At 36 months, the mean number of enhancing lesions remained very low in the overall cohort, Dr. Comi said. Almost 90% of patients were free of gadolinium-enhancing lesions, and annualized relapse rates were low in all groups. In addition, between 70% and 78% of patients treated for up to 36 months, depending on the group, were free of new T2 lesions on MRI since month 24.

The most frequent adverse events were nasopharyngitis, influenza, headache, and fatigue. Most of the adverse events frequently reported in the first 6 months of the core study appeared to decline over the period of follow-up, Dr. Comi said.

Interestingly, given the benefits of a potential oral agent, only 73% of patients completed the 3 years. Many of the dropouts occurred in the early part of the extension, he noted. The most common reason for discontinuation was adverse events (occurring in 5 of 16 patients who withdrew between months 24 and 36) and withdrawal of consent (frequently a decision by women to become pregnant).

Macular edema had been seen with fingolimod in previous transplantation trials, and there were 4 cases of suspected macular edema in this trial (1 since the month-24 analysis). However, the diagnosis was not confirmed by external review of retinal specialists. There was some elevation of hepatic enzymes, but as had been seen with other adverse events, the frequency declined over time, Dr. Comi noted.

"All of these data taken together continue to suggest that the drug is active; second, the frequency of adverse effects tends to decrease with continuation of the treatment, and there was no evidence of any new adverse effects except some reports of skin malignancies," he said.

Seven cases of skin malignancies were observed during the extension trial: 3 basal-cell carcinomas, 2 squamous-cell carcinomas, and 2 melanomas. All were in situ, and all have been treated without other complications, he said.


This potential effect will be monitored closely in phase 3 trials that are now under way. In more than 3000 patients enrolled in those trials to date, all of whom are being evaluated by dermatologists, 8 skin malignancies have been reported (with the treatment code still masked), again all in situ and all treated, Dr. Comi said. The safety monitoring board reviewing the safety data from all ongoing fingolimod studies has not indicated at this time that there is an imbalance between placebo and active-treatment groups.

"The real problem is that . . . we started a program of surveillance . . . that resulted in [an] immediate early diagnosis, so we are still [asking] whether it is because we are paying attention to the problem that we are seeing cases or whether it because there is a real excess. We don't underestimate the problem, but we need to understand," he said.

Two of the phase 3 trials are comparing fingolimod with placebo, and 1 is using an active comparator, interferon beta-1a (Avonex, Biogen). "It will be fundamental to see whether these phase 3 trials will confirm the quite good profile of the drug seen in this extension of the original trial," he told Medscape Neurology & Neurosurgery.

Continual and Prolonged Effect

Asked for comment on these results by Medscape Neurology & Neurosurgery, B. Mark Keegan, MD, a neurologist at the Mayo Clinic in Rochester, Minnesota, said, "This is an important study in the ongoing search for safe and effective oral medications for MS patients. Given MS is a long-term chronic disease, it is essential that the effects on reducing relapses and new MRI activity be continual and prolonged, and this is what the study suggests."

The study was supported by Novartis Pharma AG. Dr. Comi reports that he has received personal compensation for activities with Teva Neuroscience, Schering-Plough, and EMD Serono. Disclosures for coauthors appear in the abstract. Dr. Keegan reports no disclosures relevant to this study.

American Academy of Neurology 60th Annual Meeting: Abstract S12.005. Presented April 15, 2008.
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PostPosted: Fri Mar 15, 2013 5:47 pm    Post subject: Reply with quote

For other threads about Gilenya or fingolimod that predate this thread, please try the Search function.

Enter "Gilenya" or "fingolimod" in the window and limit your search to the "MS - Research, Articles, Abstracts, Discussion" forum. This should bring up all of the threads where those words occur.
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PostPosted: Thu Mar 28, 2013 4:00 pm    Post subject: (AAN) Early initiation of fingolimod after stopping Tysabri Reply with quote

Presented at the annual AAN conference in San Diego, March 16-23, 2013:

Quote:
[P01.199] Early Initiation of Fingolimod Treatment Reduces the Recurrence of Disease Activity after Natalizumab Discontinuation in Multiple Sclerosis

Joachim Havla, Munchen, Germany, Bjorn Tackenberg, Marburg, Germany, Kerstin Hellwig, Bochum, Germany, Markus Krumbholz, Munich, Germany, Ingrid Meinl, Munich, Germany, Florian Seitz, Marburg, Germany, Christian Eienbroecker, Marburg, Germany, Ralf Gold, Bochum, Germany, Reinhard Hohlfeld, Munich, Germany, Ingo Kleiter, Bochum, Germany, Tania Kuempfel, Munich, Germany

OBJECTIVE:

To assess the recurrence of clinical disease activity after switching from natalizumab (NAT) to fingolimod (FTY) in patients with relapsing-remitting multiple sclerosis (RRMS).

BACKGROUND:

Natalizumab (NAT, Tysabri®) is an effective therapy for relapsing-remitting multiple sclerosis (RRMS), but it carries the risk of progressive multifocal leukoencephalopathy (PML). Accordingly, fear of PML is the leading cause for discontinuation of NAT treatment. Because disease activity is likely to recur in highly active RRMS within 4-7 months after stopping NAT, early substitution of an alternative treatment is recommended. An obvious option is fingolimod (FTY, Gilenya®).

DESIGN/METHODS:

Retrospective analysis of disease activity (Annualized relapse rate (ARR) and (Gd+) lesions on magnetic resonance imaging) before, during, and after discontinuation of NAT in patients, who switched to FTY ≤24 weeks after cessation of NAT (FTY group, n=32) compared to patients who remained without therapy for at least 24 weeks (therapy free group=TFG; n=11).

RESULTS:

15 patients (47%) in the FTY group and 8 patients (73%) in the TFG had ≥1 relapses after cessation of NAT (ARR 0.8 vs. 1.8, p=0.03). 3/15 (20%) FTY patients and 7/10 (70%) patients in the TFG showed Gd+ lesions on MRI after stopping NAT (p<0.05). Patients who switched to FTY ≤12 weeks after NAT discontinuation (n=10) had a lower post-NAT ARR (0.4) compared to patients (n=22) who started FTY therapy ≥12 weeks after NAT (ARR 0.9; not significant). Most relapses in the FTY group occurred just before or within 8 weeks after starting FTY.

CONCLUSIONS:

Our observation suggests that initiation of FTY treatment after NAT discontinuation reduces the recurrence of disease activity compared to patients who remain without immunomodulatory treatment. In the FTY group the ARR tended to depend on the time interval between discontinuation of NAT and initiation of FTY.

Category - MS and Related Diseases: Clinical Science


Session P01: Multiple Sclerosis: MS Treatments
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PostPosted: Fri Mar 29, 2013 6:11 pm    Post subject: (AAN) Switching from Tysabri to Gilenya in MS--French study Reply with quote

Presented at the annual AAN conference in San Diego, March 16-23, 2013:

Quote:
[S41.002] ENIGM: A French Observational Study about Switching from Natalizumab to Fingolimod in Multiple Sclerosis

Mikael Cohen, Nice, France, Elisabeth Maillart, Paris, France, Caroline Papeix, Paris, France, Sandra Vukusic, Lyon, France, David Brassat, Toulouse, France, Jerome De Seze, Strasbourg, Cedex, France, Ayman Tourbah, Paris, Cedex, France, Sandrine Wiertlewski, Nantes, France, David Laplaud, Nantes, France, Sylvie Courtois, Mulhouse, France, Faycal Derouiche, Mulhouse, France, Loic Chambaud, Mulhouse, Clotilde Boulay, Mulhouse, France, Bruno Brochet, Bordeaux, France, Marc Debouverie, Nancy, France, Olivier Casez, Grenoble, France, Olivier Heinzlef, Paris, France, Jean Ouallet, San Francisco, CA, Bruno Stankoff, Paris, France, Giovanni Castelnovo, Nimes, France, Emmanuelle Le Page, Rennes, France, Gilles Defer, Caen, France, Nathalie Derache, Caen, France, Olivier Anne, Bordeaux, France, Eric Berger, Besancon, France, Lucien Rumbach, Besancon, France, Jean-Phillippe Camdessanche, Saint-Etienne, France, Audrey Kopf, Paris, France, Marie Fleury, Strasbourg, France, Irina Malikova, Marseille, France, Jean Pelletier, Marseille, France, Abdullatif Al Khedr, Amiens, France, Christian Zaenker, Colmar, France, Gilles Edan, Cedex, France, Thibault Moreau, Rousse, France, Agnes Fromont, Dijon, France, Audrey Rico, Marseille, France, Frederic Blanc, Strasbourg, France, Nicolas Collongues, Strasbourg, France, Pascal Barth, Saverne, France, Pierre Louiset, Bordeaux, France, Sophie Pittion, Metz, France, Pierre Clavelou, Clermont Ferrand, France, Frederic Taithe, Clermont Ferrand, France, Patrick Vermersch, Lille, France, Helene Zephir, Lille, France, Alain Creange, Creteil, France, Olivier Gout, Paris, France, Anne Marie Guennoc, Tours, France, Marc Coustans, Quimper, France, Gregory Taurin, Rennes, France, Francois Lallement, Rennes, France, Francois Rouhart, Brest Cedex, France, William Camu, Montpellier, France, Eric Thouvenot, Montpellier, France, Pierre Labauge, Nimes, France, Dominique Dive, Liege, Belgium, Pierrette Seeldrayers, Charleroi, Belgium, Christine Lebrun Frenay, Nice, France

OBJECTIVE:

To collect prospectively safety and efficacy outcomes in relapsing remitting multiple sclerosis (RRMS) patients switching from natalizumab (NTZ) to fingolimod (FTY) therapy.

BACKGROUND:

Switching from NTZ to FTY can be considered as an option regarding tolerance, efficacy, or risk of developing progressive multifocal leukoencephalopathy (PML) under NTZ. Depending on patients or neurologists, a switch can be proposed either after two years of NTZ infusions or earlier in case of adverse events. However, safety of such strategies haven't been evaluated.

DESIGN/METHODS:

This is a French observational multicentric study. Patients for which a switching strategy from NTZ to FTY was planned were prospectively included. Demographical data, clinical data about NTZ treatment period, duration and management of washout period (WP), relapses during WP and after initiation of FTY were anonymously collected.

RESULTS:

36 centers treating 4500 patients with NTZ participated. 177 patients switched to FTY after an average of 36 infusions (F/M sex ratio: 2.5; age 40y; EDSS 3.6). 72% were seropositive for JC virus and 50% were classified in the highest risk category for developing PML. EDSS score remained stable under treatment. During the WP, 55% patients did not receive any treatment and 45% received sequential methylprednisolone infusions. 65% presented a relapse. The only predictive factor was the duration of the WP (p=0.002). At the initiation of FTY, EDSS had slightly but significantly worsened (3.7; p=0.004). 33% of patients who received FTY for more than 6 months presented at least one relapse. 3.3% stopped FTY for efficacy or tolerance issues.

CONCLUSIONS:

In this study, switching from NTZ to FTY is not safe enough to be considered as a routine option in treatment strategy. Use of immunomodulatory drugs didn't prevent the risk of relapse during WP. No predictive factor of relapse under FTY has been identified yet in this cohort.
____________________________

Supported by: The ENIGM (Enquete Nationale concernant l'Introduction du finGolimod en relais au natalizuMab) study was conducted on behalf the Club Francophone de la Sclerose en Plaques (CFSEP).
Category - MS and Related Diseases: Clinical Science

Thursday, March 21, 2013 12:15 PM

Session S41: Multiple Sclerosis: Clinical Trials II
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PostPosted: Thu Apr 04, 2013 6:24 pm    Post subject: (AAN) Efficacy of Gilenya in MS patients... Reply with quote

Presented at the AAN conference in San Diego, March 16-23, 2013:

Quote:
P01.204] Efficacy of Fingolimod Treatment in Multiple Sclerosis Patients: A Multicenter Experience in Clinical Practice

Rocco Totaro, L'Aquila, Italy, Gianfranco Costantino, Foggia, Italy, Paolo Bellantonio, Pozzilli, Italy, Maria Rossi, L'Aquila, Italy, Caterina Di Carmine, L'Aquila, Italy, Aurora Fuiani, Foggia, Italy, Ciro Mundi, Foggia, Italy, Stefano Ruggieri, Rome, Italy, Antonio Carolei, L' Aquila, Italy

OBJECTIVE:

To evaluate efficacy of fingolimod in a cohort of relapsing-remitting multiple sclerosis (MS) patients treated with fingolimod in a real clinical practice setting.

BACKGROUND:

Fingolimod is the first oral drug approved for the treatment of MS patients. Fingolimod use in clinical practice is reserved to patients with inadequate response to other disease-modifying drugs or with a rapidly evolving disease. No data about the real impact in patients who satisfy eligibility criteria are reported.

DESIGN/METHODS:

We report data of the first consecutive 84 patients receiving fingolimod at 3 Italian MS centers. Patients have been chosen in accord to AIFA Eligibility Criteria. Main efficacy endpoints were the proportion of patients free from relapses, from MRI activity, from EDSS progression, and from any disease activity.

RESULTS:

Out of 84 patients included, 58 were women and 26 men. Mean age was 38.5±8.3 years. Sixteen patients were treated with natalizumab before starting fingolimod and were shifted to this treatment because of risk of progressive multifocal leukoencephalopaty.Fourteen patients received fingolimod <6 months, 21 patients received treatment between 6 and 11 months, 42 patients between 12 and 18 months, and 7 patients >18 months. Therapy was stopped in 4 patients (4.8%) within the first 6 months of treatment. In 2 patients [therapy] was stopped due to inefficacy and in 2 patients due [to] their decision.

Mean EDSS score at baseline was 2.4±1.1, at 6 months it decreased in 10 patients while [it] increased in 1 patient, at 12 and 18 months it remained stable. During the treatment, 95.2% of patients were relapse-free, 86.8% were free [from] MRI activity, 98.8% were free from EDSS progression, and 90.5% were free from any disease activity.

CONCLUSIONS:

In clinical practice, fingolimod is effective in reducing disease activity and progression of disability over the treatment period. The amount of efficacy was more pronounced than reported in the pivotal registration trials.

Category - MS and Related Diseases: Clinical Science


Session P01: Multiple Sclerosis: MS Treatments
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PostPosted: Tue Apr 16, 2013 7:54 pm    Post subject: Gilenya's marketing campaign Reply with quote

From the New York Times, April 3, 2013:

Quote:
Advertising

An MS Drug Takes a Feisty Approach Aimed at Younger Patients

By ELIZABETH OLSON

THE Swiss drug maker Novartis is taking a sassy new tack to win converts to its oral multiple sclerosis treatment, Gilenya. Its “Hey MS, Take This!” campaign shows patients sticking out their tongues with Gilenya capsules on them to show their willingness to fight back against the neurological condition.

The campaign, which begins this week, is aimed at younger people with multiple sclerosis, a chronic autoimmune disease with symptoms like fatigue, difficulty in walking and blurred or double vision. The campaign will be in national print outlets, including a half-dozen national magazines like People, Shape and Self, and on the Web sites of women’s magazine[s]. A television-style online video will also be available on social media outlets.

“MS strikes in the prime of life, and many patients use the Web and social media to connect,” said Dagmar Rosa-Bjorkeson, head of Novartis’s multiple sclerosis unit. “Many are now being diagnosed in their 20s and 30s, and early treatment makes the most impact, so we are trying to target those people who are active and digitally savvy.”

The campaign’s upbeat tone comes, Ms. Rosa-Bjorkeson said, from sentiments patients expressed on blogs and other forms of social media where “people were saying that ‘this disease is not going to stop me.’ ”

“Those were spirited words, with an edginess and power to them that wound up giving the campaign a bolder tone,” she said.

Novartis is trying to set the Gilenya campaign apart from other pharmaceutical advertising.

All such ads must conform to federal regulatory strictures that consumers receive balanced information that not only includes the drug’s effectiveness but also enumerates its risks in consumer-friendly language.

“Since it was approved in 1997, direct contact advertising with consumers has led to a fairly conservative pharma culture,” said Bill Daddi, president of Daddi Brand Communications. “It sometimes leads to people looking at the ads to ask, ‘What’s worse, the symptoms or the cure?’ ”

“But it also encourages people to speak up about their symptoms, which they didn’t always do before,” he said.

Gilenya is in an increasingly crowded treatment market. It is one of three oral therapies that have been approved recently to treat multiple sclerosis, a condition thought to occur when the body’s immune system attacks its nerve fiber insulation.

The Novartis drug is aimed at the most prevalent form of multiple sclerosis, called relapsing, in which the condition can flare up and intensify impairment of neurological function. Novartis says one daily dose of Gilenya helps slow the advance of physical problems that can be brought on by the disease, including shrinkage of the brain.

...

Since its approval by the Food and Drug Administration in September 2010, Gilenya has been used by 28,000 multiple sclerosis patients in the United States. Last year its sales reached $1.2 billion. It competes with products from Bayer, Biogen Idec and Teva in the nearly $9 billion annual market in the United States.

Novartis did not disclose its spending on the Gilenya campaign. But last year, its pharmaceutical ad spending was $95.3 million, according to figures from Kantar Media, a unit of WPP, down from $116.6 million in 2011.

Two-thirds of those with multiple sclerosis are women, and many receive the diagnosis between ages 25 and 44, according to Ms. Rosa-Bjorkeson. A majority of patients use blogs, Facebook, Twitter and YouTube to find information and to connect with fellow sufferers, she said.

The company is using some real patient stories, gleaned from about a dozen patients, on its Web site, gilenya.com, and in brochures and other marketing materials, she said. It plans to add to this as the campaign reaches more people with multiple sclerosis, she said.

“It’s all about attitude,” explained Mike Devlin, creative director of the campaign’s ad agency, Draftfcb, part of the Interpublic Group, which interviewed the multiple sclerosis patients. “There were a lot of nuggets that reflected their voice and attitude, and an outpouring about the impact Gilenya had on their lives.” A 60-second commercial and print ads, he said, “are designed to get people thinking about their treatment choices.”

Featuring real patients “is a contemporary way to get patients to recognize their symptoms and to be more in control,” said Jeff Rothstein, a partner at Cult Health, a Cult360 ad agency. “But pharma ads have to tread a fine line so they are not seen as promoting the idea that patients should just ask the doctor to write a prescription for the drug.”

This is the first broad marketing campaign for Gilenya, which Novartis licensed in 1997 from Mitsubishi Tanabe Pharma and tested in clinical trials. The company says trials have shown the drug to be more effective than interferon treatments, but serious side effects include elevated liver enzymes, headaches, diarrhea and back pain.

Shortly after Gilenya entered the market, Novartis conducted a smaller marketing effort, with ads in magazines aimed at those with multiple sclerosis as well as a limited placement in national magazines.

Its new campaign emphasizes empowered young patients, who use phrases like “No needles for me” and “Take this, you bully” to show their defiant attitude as they cope with the disease.

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PostPosted: Mon Jul 22, 2013 4:51 pm    Post subject: FTY720 may help prevent heart failure Reply with quote

From Medical News Today, July 19, 2013:

Quote:
Drug Approved For MS Shows Promise For Preventing Heart Failure


A drug already approved to treat multiple sclerosis may also hold promise for treating cardiac hypertrophy, or thickening of the cardiac muscle - a disorder that often leads to heart failure, researchers at the University of Illinois at Chicago College of Medicine report.

The findings are published in the journal Circulation: Heart Failure.

Cardiac hypertrophy is a slow thickening of the heart muscle that shrinks the interior volume of the heart, forcing the organ to work harder to pump a diminishing volume of blood.

"There comes a day when the heart just can't keep up any more, and it fails," says R. John Solaro, UIC distinguished university professor and head of physiology and biophysics.

Cardiac hypertrophy, which afflicts one in 500 people, can be caused by high blood pressure or inherited through genes that control contraction of the heart.

Solaro and his colleagues believe that if the thickening of the heart muscle could be slowed, or maybe even reversed, heart failure could be prevented.

Solaro and his UIC colleague Yunbo Ke, research assistant professor of physiology and biophysics, were interested in a chemical derived from a fungus used in traditional Chinese medicine as an eternal-youth nostrum. That compound, designated FTY-720, has been developed into a drug to treat multiple sclerosis and is a chemical cousin to the drug most widely used to suppress the immune system and prevent organ rejection in transplant patients.

The substance, Solaro said, "mimics certain lipids in the body that play a role in the development of cardiac hypertrophy."

Using an experimental mouse model of cardiac hypertrophy, Solaro and his team found that FTY-720 significantly reduced heart mass; lessened fibrosis, or stiffening of the heart muscle; and improved overall cardiac function in the mice that received the drug.

The researchers also showed that the drug inhibits expression of several genes involved in cardiac hypertrophy.

"We saw that FTY-720 blocked the activity of a protein we know is involved in causing heart-cell thickening," said Solaro. When that protein is blocked, he said, collagen and other proteins involved in heart-cell thickening are also down-regulated.

Collagen, a fibrous protein found between heart cells, causes the heart muscle to become stiff. Collagen is often overabundant in people with cardiac hypertrophy.

"When the heart muscle is stiff, it actually takes effort to relax the heart and allow blood to flow into the ventricles, so this is another way this disease causes the heart to work harder than it should have to," Solaro said.

"FTY-720 is a potential therapy to treat this disease and prevent heart failure for people where the disease is acquired through high blood pressure, and possibly inherited hypertrophy as well," he said.

__________________________

References:

In addition to Solaro and Ke of UIC, other contributors to the new study were Wei Liu, Hoyee Tsui, Sanjoy Chowdhury, Leo Zeef, Qing-Jun Meng, Mark Travis, Min Zi, Sukhpal Prehar, Andrew Berry, Niel Hanley, Ludwig Neyses, Delvac Oceandy, Elizabeth Cartwright, Ming Lei and Xin Wang of the University of Manchester in the U.K. and Rui-Ping Xiao of the Institute of Molecular Medicine at Peking University in Beijing.

The study was supported in part by NIH grants PO1 HL 062426 and RO1 HL 064035; grant G10002647 from the Medical Research Council of Great Britain; and UIC’s Center for Clinical and Translational Science grant UL1RR029879.

University of Illinois at Chicago
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PostPosted: Tue Jul 30, 2013 4:30 pm    Post subject: MS patient on Gilenya develops PML Reply with quote

Reuters press release, July 30, 2013:

Quote:
Patient taking Novartis MS pill developed rare disease

* Patient took Novartis' Gilenya MS pill
* Developed progressive viral disease
* First incidence in 71,000 patients
* Gilenya facing competition from Biogen's Tecfidera

ZURICH, July 30 (Reuters) - A patient taking Novartis' multiple sclerosis pill Gilenya developed a rare and potentially fatal viral disease, the Swiss drugmaker said on Tuesday, an unexpected setback as it faces growing competition from new oral treatments.

Gilenya is one of Novartis' big new drug hopes, growing 66 percent in the second quarter to $468 million. But the drug faces competition from new medicines such as Biogen Idec's Tecfidera.

Novartis said it had been informed of a case of progressive multifocal leukoencephalopathy (PML) in a patient who had been taking Gilenya for MS for seven months.

It said it was working with the reporting physician to understand all possible contributing factors, including those beyond treatment, given several atypical features of the case.

"The course of the underlying neurological disease was rapid with some atypical findings for MS on the MRI scans of the brain and spinal cord, as well as some unusual clinical features," Novartis said in a statement.

Novartis said all previously reported cases of PML among the approximately 71,000 patients treated with Gilenya thus far had been attributed to prior treatment with Biogen Idec's Tysabri, which bears a known risk of PML.

Deutsche bank analyst Tim Race said the case may provoke some concerns about Gilenya's future growth potential. But he noted the incidence of reported PML cases for Gilenya has so far been extremely low.
"By the time there was a similar level of patient experience with Tysabri there had been 298 cases reported. Thus, even if the risk proves to be real it is likely to be of a very different order of magnitude," Race said in a note.

Shares in Novartis were trading down 0.8 percent at 66.10 Swiss francs by 0904 GMT, compared to a 0.4 percent weaker European healthcare sector.


The article can be seen here.
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PostPosted: Mon Sep 02, 2013 4:30 pm    Post subject: Gilenya under FDA investigation for PML case Reply with quote

From PharmTech.com, September 2, 2013:

Quote:
Novartis' MS Drug Gilenya Under FDA Investigation for PML Case

By: Adeline Siew, PhD

FDA has issued issued a safety alert after a patient with multiple sclerosis (MS) in Europe developed a rare and serious brain infection known as progressive multifocal leukoencephalopathy (PML) following treatment with Gilenya (fingolimod). According to the agency, this is the first case of PML in a patient taking Gilenya who had not previously received Tysabri (natalizumab, marketed by Biogen Idec), which is an MS drug associated with a higher risk of PML.

FDA warns patients not to stop taking Gilenya without consulting their doctors. FDA is working with Novartis to investigate this case and will review all available information about this occurrence. The final conclusions and recommendations will be announced after completion of the evaluation.

Gilenya was approved in 2010 as the first oral treatment for relapsing forms of MS and approximately 71,000 patients worldwide have been treated since its launch, according to Novartis. Novartis first reported this new case of PML in July.



Quote:
ABOUT THE AUTHOR

Adeline Siew, PhD

Adeline Siew is the editor of Pharmaceutical Technology Europe. Adeline Siew joined the editorial team of Pharmaceutical Technology and BioPharm International in 2012. She has a pharmacy degree from the University of Strathclyde and a PhD in Pharmaceutics (Drug Delivery) from the School of Pharmacy, University of London, where she also did her post doctorate research. She previously worked as an editor at IMS Health and BioMed Central before joining Advanstar's Pharm Sciences group.


The article can be seen here.
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PostPosted: Tue Sep 03, 2013 4:18 pm    Post subject: More on this Reply with quote

From Doctors Guide Alerts, August 29, 2013:

Quote:
FDA Investigating Rare Brain Infection in Patient Taking Fingolimod

ROCKVILLE, Md -- August 29, 2013 -- The US Food and Drug Administration (FDA) is alerting the public that a patient in Europe diagnosed with possible multiple sclerosis (MS) has developed a rare and serious brain infection after taking the drug fingolimod (Gilenya).

This is the first case of progressive multifocal leukoencephalopathy (PML) reported following the administration of fingolimod to a patient who had not previously received natalizumab (Tysabri).

The FDA is providing this alert while they continue to investigate the PML case, and are working with the manufacturer of fingolimod, Novartis, to obtain and review all available information about this occurrence. The FDA will communicate their final conclusions and recommendations after the evaluation is complete.

The patient who developed PML received nearly 8 months of fingolimod treatment before being diagnosed with PML. The patient had been treated with interferon beta-1a and azathioprine for 1 month before initiating fingolimod treatment; those medications were stopped when fingolimod was started. The patient also received multiple courses of intravenous corticosteroids for several months before and during fingolimod treatment. The diagnosis was made based on clinical symptoms and the detection of John Cunningham (JC) viral DNA in the cerebrospinal fluid. Fingolimod treatment was stopped.

The FDA urges healthcare professionals and patients to report side effects involving fingolimod to the FDA MedWatch program, using the contact information below:

Contact FDA

1-800-332-1088

1-800-FDA-0178 Fax



SOURCE: US Food and Drug Administration
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