Alkermes plc (Nasdaq: ALKS) and Biogen Inc. (Nasdaq: BIIB) announced on 2/25/19 that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for diroximel fumarate (BIIB098), a novel oral fumarate in development for the treatment of relapsing forms of multiple sclerosis (MS). The NDA has been assigned a PDUFA (Prescription Drug User Fee Act) target action date in the fourth quarter of 2019. If approved, Biogen intends to market diroximel fumarate under the brand name VUMERITY™, which has been conditionally accepted by the FDA and will be confirmed upon approval.
Alkermes is seeking approval of diroximel fumarate under the 505(b)(2) regulatory pathway, referencing Biogen’s dimethyl fumarate data. The NDA submission includes data from EVOLVE-MS-1, a Phase 3, open-label, two-year safety study in relapsing-remitting MS (RRMS) patients. It is hypothesized that the distinct chemical structure of diroximel fumarate may impact its gastrointestinal (GI) tolerability. Alkermes is conducting EVOLVE-MS-2, a head-to-head GI tolerability study versus dimethyl fumarate, with results expected later this year.
While the mechanism of action of diroximel fumarate is not fully understood, it is known to rapidly convert to monomethyl fumarate in the body. Its immunomodulatory nature and anti-oxidant properties could help to protect the myelin sheath that insulates nerve fibers without leading to immune suppression. Biogen made a $50 million milestone payment to Alkermes in June of 2018 following review of preliminary GI tolerability data for the drug. Under terms of their agreement, Alkermes may also receive a $150 million milestone payment from Biogen upon FDA approval, on or before 12/31/21, of the NDA for diroximel fumarate.