The FDA has granted the go-ahead to Biogen and Alkermes’ diroximel fumarate, which will be marketed as Vumerity, for the treatment of relapsing-remitting and secondary progressive MS, as well as clinically isolated syndrome.
Alfred Sandrock, Jr., MD, PhD
Biogen and Alkermes have announced that the FDA has approved their multiple sclerosis (MS) agent diroximel fumarate (Vumerity) for the treatment of relapsing forms of MS, including relapsing-remitting and secondary progressive disease, as well as clinically isolated syndrome (CIS).1
Previously known as BIIB098 and ALKS 8700, the agent’s new drug application (NDA) was supported by findings from the EVOLVE-MS-1 study (NCT02634307), an open-label phase 3 safety trial of the therapy in approximately 500 patients with relapsing-remitting MS.
“The FDA’s approval of Vumerity delivers on Biogen’s commitment to pursue new therapies that may provide meaningful impact for people living with relapsing MS, and we look forward to bringing it to the MS community as an additional treatment option,” Alfred Sandrock, Jr., MD, PhD, executive vice president, research and development, and chief medical officer, Biogen, said in a statement. “Vumerity is a novel fumarate that offers the well-characterized efficacy of Tecfidera and has been studied for improved patient-reported gastrointestinal tolerability.”
EVOLVE-MS-1 ultimately 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.2
Exploratory interim data from EVOLVE-MS-1, presented at the 2018 American Academy of Neurology Annual Meeting, showed that the annualized relapse rates (ARR) for 570 participants was .016 at 1 year. Of these patients, 152 were also assessed by MRI for changes in the number and size of gadolinium-enhancing lesions (mean: 0.3; standard deviation [SD]: 1.1), new T1-hypointesnse lesions (mean: 1.8; SD: 4.2), and new/enlarging T2 lesions (mean: 2.8; SD: 5.9) compared to baseline. The MRI analysis showed a significant reduction in the number of gadolinium-enhancing lesions and T1 and T2 lesions compared to baseline. The number of gadolinium-enhancing lesions in 374 participants with available MRI data decreased 80% compared to baseline, from a mean 1.5 to 0.3 (P
“The approval of Vumerity for relapsing MS marks the culmination of a multi-year development program and is the latest milestone in our mission to develop new treatments for patients living with chronic central nervous system disorders,” said Craig Hopkinson, MD, chief medical officer and senior vice president of medicines development and medical affairs, Alkermes, in a statement. “We are grateful to the patients and study investigators who have participated in our Vumerity clinical trials and we look forward to working with our collaboration partners at Biogen to make this new treatment available to patients.”
Additionally, Alkermes conducted EVOLVE-MS-2
(NCT03093324), a head-to-head gastrointestinal tolerability study comparing diroximel fumarate with dimethyl fumarate. The double-blind, phase 3 study included 506 patients with RRMS, randomized 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 were 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). Findings suggested that it is superior to dimethyl fumarate in patients with relapsing MS, who experienced fewer days of GI symptoms with intensity scores ≥2 on the IGISIS compared to those on dimethyl fumarate (P
Biogen holds the exclusive, worldwide license to commercialize diroximel fumarate and issued its intention to make it available in the United States in the near future.
“MS is a heterogeneous disease, and real-world patient circumstances can vary, reinforcing the benefits of having therapeutic choices to support the diverse range of treatment considerations,” said Robert Naismith, MD, professor of neurology, Washington University School of Medicine in St. Louis, in a statement. “Throughout its clinical development program, VUMERITY has demonstrated a desirable therapeutic profile, making it a compelling new option for patients.”
1. Biogen and Alkermes Announce FDA Approval of VUMERITY™ (diroximel fumarate) for Multiple Sclerosis [press release]. Cambridge, MA, and Dublin, Ireland: Biogen and Alkermes; Published October 30, 2019. globenewswire.com/news-release/2019/10/30/1937769/0/en/Biogen-and-Alkermes-Announce-FDA-Approval-of-VUMERITY-diroximel-fumarate-for-Multiple-Sclerosis.html. Accessed October 30, 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. Leigh-Pemberton R, Naismith R, Kandinov B, et al. MRI and Relapse Results for ALKS 8700 in Patients with relapsing Remitting Multiple Sclerosis: 1-year Interim Results from the Phase 3 EVOLVE-MS-1 Study. Poster presented at the 2018 American Academy of Neurology Annual Meeting; April 24, 2018; Los Angeles, Calif. Emerging Science Abstract 006.
4. Diroximel Fumarate Demonstrated Significantly Improved Gastrointestinal Tolerability Profile Compared to Dimethyl Fumarate in Patients with Multiple Sclerosis [press release]. Dublin, Ireland, and Cambridge, MA: Alkermes and Biogen; Published July 30, 2019. globenewswire.com/news-release/2019/07/30/1893560/0/en/Diroximel-Fumarate-Demonstrated-Significantly-Improved-Gastrointestinal-Tolerability-Profile-Compared-to-Dimethyl-Fumarate-in-Patients-with-Multiple-Sclerosis.html. Accessed October 30, 2019.