Positive Study Results with Oral FTY720 Leads to Granting of Priority Review Status by FDA

In January 2010, the results from two large Phase III trials with oral FTY720 (fingolimod) were published in The New England Journal of Medicine. According to a press release from Novartis Pharmaceuticals Corporation (makers of FTY720), the TRANSFORMS and FREEDOMS studies showed positive results in reducing relapses, disability progression, and MRI lesions when MS patients were given FTY720.

TRANSFORMS was a one-year study with 1,292 individuals with MS. Participants were given either FTY720 or interferon beta-1a (Avonex®). FREEDOMS was a two-year study with 1,272 MS patients. This latter study compared FTY720 with a placebo. Two dose levels were used in both studies (0.5 mg and 1.25 mg). Given the best benefit-risk profile, Novartis will be seeking FDA (and European) approval for the smaller dose of 0.5 mg taken once daily.

In the lower-dose group of the one and two-year studies, relapses were reduced by 52 percent and 54 percent, respectively. Also in both studies, the lower dose reduced the risk of disability progression, as well as reduced brain lesion activity and brain volume loss, as measured by magnetic resonance imaging (MRI).

In February 2010, Novartis announced that FTY720, now given the new brand name of Gilenia®, had been granted priority review status by the FDA. This designation reduces the FDA’s review process from 10 months down to six months. The drug was submitted for review in December 2009, so a decision on the approval of FTY720 could come as early as June 2010.

Such a decision would make FTY720 the first approved disease-modifying therapy taken orally (by mouth) for the treatment of MS. However, Novartis cautions that this investigational drug contains an ingredient which has not been approved before (a “New Molecular Entity”), and this may require an extension of the review process beyond the anticipated June 2010 deadline*.

FTY720 is from a new class of drugs referred to as “sphingosine 1-phosphate (S1P) receptor modulators.” It works by preventing the release of certain lymphocytes (immune system cells) from the lymph nodes, so these damaging cells cannot reach the brain. According to Novartis, FTY720 reduces inflammation and may also have a beneficial effect on cells in the central nervous system (CNS).

The most commonly reported side effects from both the treated and control groups were inflammation of the nasal passages and upper part of the throat (nasopharyngitis), headache, and fatigue. Drug-related adverse events included: a reduction in heart rate (dose-related and transient); infrequent transient AV conduction block of the heart; a mild increase in blood pressure; macular edema (an eye condition that can affect vision, more common with the higher dose); and reversible elevation of liver enzymes.

*Updated: June 8, 2010:The FDA has decided to extend its review period of FTY720 by three months, to September 2010. This extension was anticipated by Novartis, the pharmaceutical company that has been developing the drug. This extension allows more time for the FDA to review further analysis of the study results, which Novartis provided following a request from the FDA. Novartis states that this clinical trial program is the largest ever submitted to the FDA for an MS disease-modifying therapy. No additional clinical trials were requested. The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee will still meet on June 10, 2010 to discuss the risks and benefits of FTY720’s new active ingredient (a “New Molecular Entity”). A decision on the drug’s approval is not expected until September.