Saturday, December 13, 2008

FTY720 (fingolimod) Research information (Oral Drug)

This was forwarded to me via the MS Society. I wasnted to share it as I think it's great news. This means we could possibly see FDA approval for an ORAL drug soon!

December 12, 2008

Oral FTY720 (Fingolimod) Reduced Relapse Rate More Effectively Than Avonex in Initial Results of One-Year Study in Relapsing-Remitting MS

The experimental oral drug FTY720 (fingolimod, Novartis) reduced relapses significantly more than Avonex® (interferon beta-1a, Biogen Idec) in a one-year study involving 1,292 people with relapsing-remitting MS. Serious adverse events in the FTY720 group included two deaths from herpes infections and seven cases of localized skin cancer. These initial results are reported in a press release from Novartis, which notes that analysis of these data is ongoing and that two other large-scale, phase 3 trials of the drug are ongoing. The company expects to submit an application to the FDA for approval by the end of 2009.

Background: FTY720 binds to a docking site (sphingosine-1-phosphate receptor, or S1P receptor) on immune cells, including T cells and B cells, that have been implicated in causing nervous system damage in MS. The drug appears to induce immune cells to remain in lymph nodes, where they can do little harm, preventing them from migrating into the brain and spinal cord. Promising phase 2 study results were published by Ludwig Kappos, MD (University Hospital, Basel, Switzerland) and colleagues in The New England Journal of Medicine (2006;355(11):1124-1139).

This one-year, phase 3 study – also known as TRANSFORMS – is one of three studies of FTY720 in relapsing-remitting MS. The company says that it expects data from two other studies – FREEDOMS and FREEDOMS II (two-year, placebo-controlled, Phase III studies that are assessing the impact of FTY720 on reducing relapses and slowing the progression of disability) – to be available in 2009. Another study, INFORMS, is evaluating the effectiveness of this drug in primary-progressive MS.

This Study: Investigators worldwide recruited 1292 people with relapsing-remitting MS. Participants were randomly assigned to receive either one of two doses (.5 mg/day FTY720 or 1.25 mg/day FTY720), or Avonex (30 mcg/week injected intramuscularly) for 12 months. The study’s primary endpoint was to compare the effectiveness of treatments in reducing the relapse rate. Secondary endpoints included comparing the proportion of relapse-free patients, drug safety and tolerability, and disease activity as observed on MRI scans. There was no assessment of neurologic disability and no evaluation of efficacy beyond one year.

The company’s press release reports on the primary outcome and drug safety and tolerability. The annualized relapse rate in those taking the lower dose of FTY720 was 0.16, compared to 0.33 in those on Avonex (a comparative reduction of 52%). Those taking the higher dose of FTY720 experienced an annualized relapse rate of 0.20 (a reduction of 38% compared with Avonex). No statistically significant difference was seen between the two FTY720 doses.

Safety: The proportion of participants discontinuing treatment during the study was 10% in the FTY720 0.5 mg group, 15% in the FTY720 1.25 mg group, and 12% in the Avonex group.

Two deaths from herpes infections occurred in the group taking the higher dose of FTY720. Seven cases of localized skin cancer occurred in the FTY720 groups, including three melanomas, and one (squamous cell carcinoma) in the Avonex group. According to the company, all skin lesions were successfully removed. .Eight cases of macular edema (swelling of the center of the retina) were seen in the FTY720 groups and one in the Avonex group. The additional clinical studies underway should help clarify whether these events are related to the experimental treatment.

The most commonly reported adverse events were headache, nasal inflammation, and fatigue, which occurred in more than 10% of participants in all three groups. Influenza-like symptoms occurred in 4% of the FTY720 groups and in 37% of the Avonex group.

Conclusion: The company is continuing to analyze the data and plans both to report fully at a scientific meeting in 2009 and to submit an application for FDA approval by the end of 2009. “It is good to see this oral drug advance through the MS pipeline,” says John Richert, MD, executive vice president for research & clinical programs at the National MS Society. “ We are eager to see longer term safety and efficacy data that also include the effects of FTY720 on measures of disability.”

-- Research and Clinical Programs Department

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