FDA and EMA to Review Ozanimod as Possible Oral Therapy for Relapsing MS

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) both agreed to review for possible approval ozanimod, Celgene‘s investigational oral therapy for relapsing forms of multiple sclerosis (MS).

An FDA decision on the company’s New Drug Application for ozanimod is expected on or before March 25, 2020. A ruling on the Marketing Authorization Application given the EMA — specifying approval as a treatment for relapsing-remitting MS (RRMS) — is likely in the first half of 2020, Celgene announced in a press release.

Ozanimod, formerly known as RPC1063, is an immunomodulator compound that works by selectively binding to sphingosine 1-phosphate (S1PR1) and 5 (S1PR5) receptors, preventing immune cells from entering the brain and causing inflammation.

Both regulatory submissions, made in March, were based on promising data from two multicenter, randomized, double-blind, and active-controlled trials: the SUNBEAM Phase 3 study (NCT02294058), and Part B of the RADIANCE Phase 2/3 trial (NCT02047734).

SUNBEAM compared the effects of ozanimod to those of Avonex (an injectable formulation of interferon beta-1a by Biogen) in treating people with relapsing forms of MS. The study enrolled 1,346 patients, who were randomly assigned to either ozanimod capsules (0.5 mg or 1.0 mg daily doses) or Avonex weekly injections for at least one year.

Results showed that people treated with ozanimod experienced fewer MS relapses and brain lesions, as well as clinically meaningful improvements in processing speed, compared to those treated with Avonex.

RADIANCE was a 120-week, two-part trial assessing the safety and efficacy of ozanimod in treating adults with relapsing-remitting MS (RRMS) compared to placebo.

In Part A (NCT01628393), 258 RRMS patients were randomly assigned to either ozanimod, at 0.5 mg or 1.0 mg once-a-day, or a placebo for 24 weeks. Results showed that ozanimod-treated patients had a lower number of brain lesions from week 12 to week 24, assessed by magnetic resonance imaging (MRI), and fewer MS relapses compared to those treated with a placebo.

Part B (NCT02047734) enrolled a total of 249 patients who had previously participated in Part A and chose to continue in a 96-week open-label extension study. Patients given ozanimod in Part A continued on the dose they had originally been assigned to, while those in the placebo group were randomly assigned to ozanimod at either its low or high dose.

After two years of treatment, most patients in both dose groups (86.5% at 0.5 mg, and 94.6% at 1.0 mg) were free of gadolinium-enhancing (GdE) lesions, or areas of active inflammation and disease activity.

Those in the original Part A treatment group also continued to experience fewer MS relapses, while those who switched to ozanimod in the open-label extension showed a substantial decrease in relapses.

Pooled data from both trials showed that ozanimod reduced the number of annual MS relapses by 42% among patients on the higher dose, and by 26% among those getting the lower dose, compared to Avonex.

At the recent 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia, the company also announced the findings of a posterior analysis of RADIANCE, examining the effects of ozanimod in preventing brain volume loss in patients from different age groups.

Results showed a lower loss of brain volume in all regions analyzed and in patients in all age groups after two years of ozanimod treatment at 1.0 mg compared to those given Avonex.

“The U.S. Food and Drug Administration and European Medicines Agency acceptances of our applications represent a crucial step forward in our efforts to bring ozanimod to people with multiple sclerosis,” Jay Backstrom, MD, chief medical officer at Celgene, said in the release.

“We believe that ozanimod has the potential to be an important option early in the treatment of relapsing forms of MS, and a best-in-class S1P receptor modulator,” Backstrom added.

Ozanimod is also in development to possibly treat ulcerative colitis and Crohn’s disease.