And the Winner Is...Novartis
By a length and a half, maybe?
Today the FDA approved fingolimod, trade name Gilenya,* the first orally administered disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. The pill, at a dosage of 0.5 mg once daily, was approved approximately 9 months after Novartis quietly submitted its NDA to the agency in December and nearly a year after Merck Serono filed its first application for an oral competitor, cladribine.
The final stretch of the approval horse race was significant for a bad stumble taken by Merck Serono, after the FDA refused to file its application in December. Speculation: the submission was incomplete. Merck Serono filed a new application 6 months later, and the company received a priority review from the agency (with an anticipated approval at the end of this year).
But also in June, an FDA panel voted overwhelmingly in favor of fingolimod's approval—at least with respect to its efficacy. Safety issues with Novartis's agent included opportunistic infections, and analysts speculated that the FDA would institute some kind of access-limiting REMS program for the drug—which has evidently come to pass, according to today's Novartis press release.**
A Health Care Provider letter at the Gilenya website describes the risk of initial bradycardia or AV block, and that all patients should be observed for 6 hours after the first dose—a cumbersome recommendation that may deter rapid, practical uptake of the drug. Warnings also exist for lymphopenia (and consequent opportunistic infections), macular edema (0.4%), respiratory compromise, elevation of liver enzymes, and fetal risk. Novartis says it will begin a 5-year global study to monitor safety-related outcomes and establish a voluntary pregnancy registry—much like what exists for Biogen Idec's Tysabri (natalizumab), which is associated with the rare, but deadly, PML.
The anticipated efficacy of Gilenya, provided here in a friendly tabulated format, is a 40% reduction in the annualized relapse rate, when the drug is compared with the standard disease-modifying treatment of Avonex (interferon-beta 1a 30 ug/wk IM).
AV = atrioventricular; NDA = new drug application; PML = progressive multifocal leukoencephalopathy; REMS = Risk Evaluation and Mitigation Strategies.
* Sometime during FDA review, Novartis changed the trade name from Gilenia to Gilenya.
** Although the FDA press release fails to mention a REMS program for Gilenya.
