Being treated with ozanimod consistently reduced disease activity in people with relapsing-remitting multiple sclerosis (RRMS), according to results of a two-year extension of a Phase 2 trial. These benefits were evident both in patients on continuous treatment throughout the study, and in those who switched to ozanimod from placebo.
Results were reported in the study, “Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study,” published in the Multiple Sclerosis Journal.
Celgene’s ozanimod is an oral therapy that blocks the mobilization of immune cells involved in the inflammatory attacks on nerve fibers and the myelin sheaths that protect them, which cause multiple sclerosis.
The two-part clinical trial, called RADIANCE (NCT01628393), evaluated the safety and efficiency of ozanimod for 120 weeks in people with RRMS in the U.S. and 12 European countries.
In part A, 258 relapsing MS patients were randomly assigned to receive a once-daily dose of ozanimod (0.5 mg or 1.0 mg) or a placebo for 24 weeks.
RADIANCE’s first part met its primary goal by showing that ozanimod treatment reduced the number of brain lesions, as determined by magnetic resonance imaging (MRI), from week 12 to week 24, and lowered the frequency of relapses in treated patients compared with placebo.
Ozanimod was seen to be safe and well-tolerated, with most treatment-related adverse events being of a mild nature. Nearly 98% of enrolled patients (252 of 258) completed part A, and only three of this group declined to continue in the study’s next phase.
In part B, 249 patients entered a 96-week open-label extension. Those originally randomized to ozanimod continued with their assigned dose (85 patients with 0.5 mg and 81 patients with 1 mg), while placebo group patients were randomized to either dose of ozanimod (41 to 0.5 mg and 42 to 1 mg).
Efficiency goals included a reduction in the mean number of brain lesions assessed by different MRI methods — gadolinium-enhancing (GdE) lesions and T2-hyperintense lesions — and in annualized relapse rates (ARR).
The extension phase was completed by 223 patients (89.6%) — 112 on the lower dose and 111 on the higher dose.
At the beginning of the extension phase, around 85% and 88% of patients receiving ozanimod 0.5 mg or 1 mg, respectively, and 58.5 to 69.0% of those on placebo were free of GdE lesions. After two years of ozanimod treatment, this percentage rose to 86.5% to 94.6% for patients in both dose groups.
The number of T2 lesions remained low in patients given ozanimod continuously, and dropped in patients switching from placebo to ozanimod. Results also showed a trend toward a greater decrease in T2 lesions in patients on the higher dose of ozanimod.
Similar results were seen in ARR. Patients already receiving ozanimod maintained low relapse rates, and those starting ozanimod in the extension phase showed a decrease in ARR. At the end of the extension phase, relapse rates were about 0.32% for the 0.5 mg group, and 0.18% for the 1.0 mg group.
Data, the study reported, showed that both doses of ozanimod had continuous efficacy over the two years, as seen in low numbers of brain lesions and low relapse rates, with an apparent greater efficiency for the 1 mg dose of ozanimod.
Regarding safety, only 3 to 4 percent of patients in both groups had at least one adverse effect associated with ozanimod treatment, with nasopharyngitis (inflammation of the nose and pharynx), upper respiratory tract infection, and increased alanine aminotransferase levels (a liver-associated enzyme) being the most common reported.
No serious opportunistic infections, and no clinically significant cardiac, pulmonary, ophthalmologic, or cancer-related adverse events occurred.
Overall, the researchers concluded that “ozanimod demonstrated sustained efficacy in participants continuing treatment up to 2 years and reached similar efficacy in participants who switched from placebo; no unexpected safety signals emerged.”
The team also noted that two larger Phase 3 clinical trials — part B of the RADIANCE study (NCT02047734) and the SUNBEAM study (NCT02294058) — involving more than 1,300 RRMS patients each, showed similar positive results. Each compared ozanimod treatment at low and high dose to Avonex (interferon β-1a).
Earlier this year, Celgene announced that the U.S. Food and Drug Administration had requested more information for its review of the company’s request to approve ozanimod as a treatment for relapsing MS.