NEW ORLEANS—Ozanimod demonstrated durable efficacy with a favorable safety profile in patients continuing ozanimod for 120 weeks or switching from placebo to ozanimod for 96 weeks, according to results of a phase II study presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “These data support the ongoing RADIANCE and SUNBEAM phase III studies,” said Brett E. Skolnick, PhD, on behalf of his study collaborators. Dr. Skolnick is an employee of Receptos, a wholly owned subsidiary of Celgene, in San Diego.
Ozanimod, an oral, once-daily immunomodulator selectively targeting sphingosine 1-phosphate (S1P) receptor-1 and -5 , is in development for relapsing multiple sclerosis (MS). “The increased receptor selectivity of ozanimod and additional pharmaceutical properties may result in a more favorable safety profile versus other nonselective and selective S1P receptor modulators,” said Dr. Skolnick.
In the completed RADIANCE Part A phase II trial, patients with relapsing MS were randomized (1:1:1) to once-daily ozanimod 0.5 mg or 1.0 mg or to placebo for 24 weeks. At week 24, patients could enter a 96-week, blinded extension phase. Patients randomized to ozanimod continued their assigned dose; 85 patients received 0.5 mg, and 81 patients received 1.0 mg. Patients administered placebo were re-randomized (1:1) to ozanimod 0.5 mg (n = 41) or 1.0 mg (n = 42). Ozanimod was dose-escalated over seven days to attenuate first-dose effects.
A total of 89% of patients taking the 0.5 mg dose and 90% of patients taking the 1.0 mg dose completed the extension study. At week 120, 89% to 91% of patients were free of gadolinium-enhancing lesions. Unadjusted annualized relapse rates were 0.31 in the 0.5 mg group and 0.18 in the 1.0 mg group. One or more treatment-emergent adverse events were seen in 79% of patients taking the 0.5 mg dose and in 76% of those taking the 1.0 mg dose. The most common adverse events were increased alanine aminotransferases, nasopharyngitis, and upper respiratory tract infection. Serious treatment-emergent adverse events were seen in 12 patients in the 0.5 mg group and in nine patients in the 1.0 mg group. Mild blunting of the normal diurnal heart rate was observed. The largest mean decrease in heart rate relative to pre-dose was 3.5 bpm at hour 6 on day 1, with no associated symptoms. No type II or 2:1 atrioventricular block was reported.
At week 120, alanine aminotransferase (ALT) levels were three or more times upper limit of normal in 6% of the 0.5 mg group and in 7% of the 1.0 mg group. In the 0.5 mg group, 2% of patients discontinued ozanimod due to increased liver transaminases. Less than 1% of patients in the 1.0 mg group discontinued ozanimod for the same reason. Between baseline and week 120, three patients in the 1.0 mg group had absolute lymphocyte counts below 200 cells/μL; none was associated with severe or serious infection. There were no notable cases of pulmonary adverse events and no cases of macular edema, malignancy-related adverse events, or serious opportunistic infections.
This study was supported by Celgene.
Cohen JA, Arnold DL, Comi G, et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):373-381.