NDA for Diroximel Fumarate for Relapsing MS Accepted by FDA

February 25, 2019

The PDUFA date for the novel oral fumarate has been set for the fourth quarter of 2019. If approved, Biogen plans to commercialize the product under the trade name Vumerity.

Craig Hopkinson, MD

The FDA has accepted a New Drug Application (NDA) for diroximel fumarate, otherwise known as BIIB098 and ALKS 8700, for the treatment of relapsing multiple sclerosis (MS), according to manufacturers Alkermes and Biogen.1

The Prescription Drug User Fee Act target date for the novel oral fumarate has been set for the fourth quarter of 2019. If approved, Biogen has announced it plans to move forward with the commercialization of the product under the trade name Vumerity, which the FDA has conditionally accepted.

"The NDA filing acceptance for diroximel fumarate further demonstrates the productive collaboration between Alkermes and Biogen and brings us closer to our shared goal of offering a new therapeutic option for people with MS," said Craig Hopkinson, MD, the chief medical officer and senior vice president of medicines development and medical affairs at Alkermes. "We believe diroximel fumarate has the potential to be a meaningful new offering for patients with MS, and we look forward to continued engagement with the FDA throughout the review process."

The NDA was accepted through the 505(b)(2) pathway and will reference Biogen’s dimethyl fumarate data, with the application including findings from the EVOLVE-MS-1 study (NCT02634307), an open-label phase 3 safety trial of the therapy in patients with relapsing-remitting MS (RRMS). The study enrolled 582 patients with a mean age of 41.4 years and a mean time since MS onset of 9.5 years. In total, 73% of patients in the trial had been previously treated for their MS. Patients were administered diroximel fumarate at a dose of 462 mg, twice daily, for up to 96 weeks.

Ultimately, the trial saw 3 patients (0.5%) discontinue due to gastrointestinal adverse events (AEs), though none were serious. From start to month 3, serious AE and AE-related discontinuation rates were 2.3% and 3.7%, respectively. “Although data are limited, [diroximel fumarate] is associated with high rates of treatment persistence within the first 3 months of initiation, and thereby demonstrates the potential to be an oral therapeutic option for patients with RRMS,” Naismith et al wrote.2

In June 2018, after Alkermes received a $50 million payment from Biogen following the preliminary data from EVOLVE-MS-1, Richard F. Pops, the company’s chief executive officer, noted that “the clinical data generated from this program underscore the potential value of BIIB098 for patients with multiple sclerosis.”3

Additionally, Alkermes is currently conducting EVOLVE-MS-2 (NCT03093324), a head-to-head gastrointestinal tolerability study comparing diroximel fumarate with dimethyl fumarate. Results from that trial are expected to read out later in 2019. EVOLVE-MS-2 will be a double-blind, phase 3 study, and will enroll roughly 420 patients with RRMS, and randomize them 1:1 to oral treatment with diroximal fumarate at 462 mg, twice daily, or dimethyl fumarate at 240 mg, twice daily, for 5 weeks. The key gastrointestinal symptoms will be examined with 2 patient-reported symptom-rating scales: the Individual GI Symptom and Impact Scale (IGISIS) and the Global GI Symptom and Impact Scale (GGISIS).

"For more than two decades Biogen has been at the forefront of delivering new medicines to MS patients," said Michael Ehlers, MD, PhD, the executive vice president of research and development at Biogen. "We are encouraged by the FDA's acceptance of the NDA for diroximel fumarate, which we believe could help elevate the treatment of this complex and often debilitating disease."

REFERENCES

1. Alkermes and Biogen Announce U.S. Food and Drug Administration Acceptance of Diroximel Fumarate New Drug Application for Multiple Sclerosis [press release]. Dublin, Ireland, and Cambridge, MA: Alkermes and Biogen; Published February 22, 2019. prnewswire.com/news-releases/alkermes-and-biogen-announce-us-food-and-drug-administration-acceptance-of-diroximel-fumarate-new-drug-application-for-multiple-sclerosis-300800855.html. Accessed February 22, 2019.

2. Naismith R, Leigh-Pemberton R, Rezendes D, et al. EVOLVE-MS-1: a phase 3, open-label, long-term safety study of ALKS 8700 in relapsing-remitting multiple sclerosis. Neurology. 2018;90(15 Suppl). P6.360.

3. Alkermes Receives $50 Million Payment From Biogen Following Review of Preliminary Gastrointestinal Tolerability Data From the Ongoing BIIB098 Clinical Development Program [press release]. Dublin, Ireland: Alkermes; Published June 6, 2018. prnewswire.com/news-releases/alkermes-receives-50-million-payment-from-biogen-following-review-of-preliminary-gastrointestinal-tolerability-data-from-the-ongoing-biib098-clinical-development-program-300660501.html. Accessed February 22, 2019.