The European Commission has endorsed the recent Committee for Medicinal Products for Human Use (CHMP) positive opinion recommending the expanded use of Swiss drug major Novartis’ drug Gilenya (fingolimod) for adult patients with highly active relapsing-remitting multiple sclerosis (RRMS).
The indication expansion will now give clinicians the flexibility to use fingolimod in the highly active RRMS group, for patients needing to switch from interferons as well as glatiramer acetate (Teva’s Copaxone) and other DMTs.
Prior to the indication expansion, fingolimod, which generated sales of nearly $2 billion last year, was limited for use in those patients with highly active RRMS not responding to an interferon.
The European Commission approval was based on a favourable review of the long-term efficacy and safety data for fingolimod and comes three years after the initial licence was granted in March 2011. Fingolimod is now approved in 80 countries and it is estimated that more than 91,500 patients have been treated with fingolimod in clinical trials and in the post-marketing setting.
.Fingolimod is the only established oral therapy approved by the UK’s drugs watchdog the National Institute for Health and Care Excellence (NICE) for the treatment of highly active RRMS that is effective across four key measures of MS disease activity – relapses, MRI lesions, brain volume loss and disability progression, the drugmaker noted. Novartis says it will work with the relevant European funding bodies to ensure that patients who meet these new criteria are able to access fingolimod in the near future.
Novartis International AG announced new data showing that more patients with relapsing multiple sclerosis treated with Gilenya (fingolimod) achieved an average annual rate of brain volume loss within the range of those expected for healthy adults of a similar age vs. those patients taking placebo. People with multiple sclerosis experience shrinkage of the brain up to three to five times faster. This acceleration starts early in people with relapsing MS, even before symptoms are apparent.
"These data are impressive as they show that Gilenya slows brain volume loss in relapsing MS patients, an important indicator of disease activity," said David Epstein, Division Head, Novartis Pharmaceuticals.
Gilenya is an oral disease modifying therapy that works on four key measures of multiple sclerosis disease activity - relapses, MRI lesions, brain volume loss and disability progression.
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Swiss drug giant Novartis said that the Committee for Medicinal Products for Human Use or CHMP has issued a positive opinion to expand the EU label for Gilenya (fingolimod) in relapsing remitting multiple sclerosis or RRMS.
The recommendation is to expand the label to include adult patients who have not responded to at least one disease-modifying therapy or DMT, including newly-approved oral DMTs. Gilenya is currently licensed in the EU for adult patients with RRMS who have not responded to treatment with interferons, or have rapidly evolving severe MS.
Novartis also announced new pooled analyses presented at the 66(th) American Academy of Neurology (AAN) Annual Meeting in Philadelphia, Pennsylvania from the pivotal FREEDOMS and FREEDOMS II trials in multiple sclerosis or MS, confirming the consistent efficacy of Gilenya across four key measures of MS (relapse rates, MRI lesions, brain volume loss and disability progression). Addressing these four measures through effective treatment and disease management is important for improving the course of MS for patients.
The pooled analyses from the FREEDOMS and FREEDOMS II trials show that in patients with high disease activity previously treated in the past year, Gilenya demonstrated significant efficacy across the certain measures.
Gilenya reduced relapses (as measured by the annualized relapse rate) by almost half (48%) compared to placebo; new T2 lesion formation was reduced by 69% compared to placebo; Gilenya reduced the rate of brain volume loss by 46% compared to placebo; using a stringent six-month disability measure, Gilenya reduced disability progression by 45% compared to placebo.
Source: RTT News Copyright © 2014 RTTNews (29/04/14)
Differential effects of fingolimod on B-cell populations in multiple sclerosis
BACKGROUND: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells.
OBJECTIVE: To clarify the effects of fingolimod on B-cell populations in patients with MS.
METHODS: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts.
RESULTS: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38int-high), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138+) among whole plasmablasts, in the patients treated with fingolimod.
CONCLUSIONS: The marked reduction of Ki-67+ memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138+ plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.
Nakamura M, Matsuoka T, Chihara N, Miyake S, Sato W, Araki M, Okamoto T, Lin Y, Ogawa M, Murata M, Aranami T, Yamamura T.
Source: Mult Scler. 2014 Feb 13. & Pubmed PMID: 24526661 (18/02/14)
The FDA is continuing to investigate a possible link between the multiple sclerosis drug Gilenya (fingolimod) and a case of a rare brain infection in a European patient.
The patient took the drug for nearly 8 months before being diagnosed with the brain infection. The FDA issued an alert at the end of August to inform the public of its investigation.
The brain infection, sometimes fatal, is called PML (progressive multifocal leukoencephalopathy). The European case is the first reported in a patient who has not previously taken the drug Tysabri (natalizumab). Tysabri is already known to be linked with a higher risk for PML.
The maker of Gilenya, Novartis, issued a statement saying it had reviewed all available evidence and that the case of PML in Europe is unlikely to be linked to the drug.
Gilenya, approved by the FDA in 2010 for relapsing MS, is taken by mouth. It is one of three new oral drugs approved in the last 3 years. The other two are Tecfidera (dimethyl fumarate) and Aubagio (teriflunomide).
In MS, the immune system attacks the central nervous system, including the brain, spinal cord, and optic nerves.
According to the FDA, patients should not quit taking Gilenya without talking to their doctor.
The FDA will issue its findings once the investigation is complete.
Source: WedMD ©2005-2013 WebMD, LLC. (21/10/13)
Novartis announced today findings from an international multiple sclerosis (MS) registry and a US health claims data base which showed the real-world superiority of Gilenya® (fingolimod) in reducing risks of relapses compared to standard therapies. These data confirm the positive results seen in clinical trials with Gilenya, and were presented at the ongoing 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark.
Relapses can make life unpredictable for patients with MS and they can potentially significantly advance an individual's level of disability. MS patients' clinical outcomes are regularly assessed and switching between disease-modifying therapies (DMTs), to reduce the rate or likelihood of a relapse, is a frequent treatment strategy.
"Controlling relapses and preventing disability are key treatment goals for patients with MS." said David Epstein, Division Head of Novartis Pharmaceuticals. "It is encouraging to see that the benefits of Gilenya, which is the only disease modifying treatment proven in clinical studies to have a superior relapse reduction compared to an active comparator, are now confirmed in the real-world setting."
The 'MSBase study', a global, longitudinal, observational registry for MS involving 60 centers in 26 countries and US administrative claims data from the 'IMS PharMetrics PlusTM Database' were interrogated for information on the impact on MS relapses of switching to either oral Gilenya or to one of the standard injectable therapies - an interferon or glatiramer acetate. Collectively, analysis of patient data from these large, real-world databases (416 patients from MSBase and 933 patients from the IMS PharMetrics PlusTM Database) showed that treatment with Gilenya reduced the annualized relapse rate and risk of relapse by approximately 50% compared to therapy with an interferon or glatiramer acetate treatment. They also showed that even amongst patients with MS who have a history of relapse, switching to Gilenya was associated with significant and clinically meaningful reductions in the number of relapses and the probability of experiencing a relapse compared to switching to an interferon or glatiramer acetate.
Following first approvals in 2010, once daily oral Gilenya is now available in more than 75 countries and more than 71,000 patients have been treated in both the clinical trial and post-marketing settings with over 87,000 patient years of exposure.
Source: MarketWatch Copyright © 2013 MarketWatch, Inc (03/10/13)
Novartis International AG has announced that new data showing the benefits of Gilenya on patient outcomes in multiple sclerosis will be presented at the 29th Congress of the European Committee for Research and Treatment in Multiple Sclerosis in Copenhagen, Denmark.
Novartis said the new four-year data from the pivotal FREEDOMS and FREEDOMS extension studies plus a separate analysis of three studies (FREEDOMS, FREEDOMS II and TRANSFORMS) will show the benefits of continued Gilenya treatment on brain volume loss compared to delayed treatment of two years. The company said these data will reinforce the correlation between brain volume loss and disability, underlining the need for addressing brain volume loss in patients with Multiple Sclerosis.
Data from international and U.S. real-world databases will also confirm the favourable effect of Gilenya on reducing relapse rates for patients with Multiple Sclerosis, the company said.
Source: RTT News Copyright © 2013 RTTNews (25/09/13)
FDA warns of PML case with Gilenya(29/08/13)
A patient being treated for multiple sclerosis and who had no history of using natalizumab (Tysabri) developed progressive multifocal leukoencephalopathy (PML) while taking fingolimod (Gilenya), the FDA said.
"This is the first case of this disease ... reported following the administration of Gilenya to a patient who had not previously received Tysabri," the agency said in a statement posted on its website.
The patient, living somewhere in Europe, had been on fingolimod for "nearly 8 months" when PML was diagnosed, according to the FDA. The agency stopped short of saying fingolimod caused the condition, however.
"We are working with Gilenya's manufacturer, Novartis, to obtain and review all available information about this occurrence," the agency said. "We will communicate our final conclusions and recommendations after our evaluation is complete."
For its part, Novartis issued a statement indicating that the firm does not believe fingolimod was responsible for PML in this case, which it had reported publicly in late July.
"Having reviewed all available information, Novartis considers that several features of this case of PML make it unlikely to be attributable to Gilenya," the company asserted.
Fingolimod was not the only drug the patient had been taking, both Novartis and the FDA noted.
"The patient had been treated with interferon beta-1a and azathioprine for 1 month before initiating Gilenya treatment; those medications were stopped when Gilenya was started. The patient also received multiple courses of intravenous corticosteroids for several months before and during Gilenya treatment," according to the FDA.
Novartis said "MRI reviewers" had examined brain scans taken before the patient started on fingolimod and determined that the patient might already have had PML, because lesions seen in the scans were "atypical" in MS.
PML results from reactivation of latent infection with the JC virus, usually in patients with acute or chronic immunosuppression. The death rate has recently been about 20%.
It was first noted in patients receiving cancer chemotherapy and later in those infected with HIV. A series of PML cases seen with natalizumab after the drug was first approved in 2004 led to its temporary removal from the market.
In the current case, the patient showed JC virus DNA in cerebrospinal fluid as well as clinical symptoms, and fingolimod was stopped, the FDA said. The agency's statement indicated the patient is still alive.
The FDA advised clinicians to report side effects involving fingolimod to its adverse-event reporting system. It also told patients currently taking the drug not to stop it without talking first with their physicians.
Source: MedPage Today © 2013 MedPage Today, LLC.(29/08/13)
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.
Source: Fox News.com ©2013 FOX News Network (30/07/13)