Efficacy and Safety of Ozanimod in the Blinded Extension (120 weeks) of RADIANCE, a Phase 2 Trial in Relapsing Multiple Sclerosis
Objectives: To further describe the safety and efficacy of once-daily ozanimod (0.5 and 1.0 mg) at 120 weeks.
Methods: In the completed RADIANCE Part A phase 2 trial (NCT01628393), patients with RMS were randomized (1:1:1) to once-daily ozanimod 0.5 mg or 1.0 mg or to placebo for 24 weeks (Cohen et al. Lancet Neurol. 2016; 15: 373). At week 24, patients could enter a 96-week, blinded extension phase. Patients randomized to ozanimod continued their assigned dose (0.5 mg, n=85; 1.0 mg, n=81); 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 7 days to attenuate first-dose effects.
Results: 89% (0.5 mg) and 90% (1.0 mg) of patients completed 120 weeks. At week 120, 89–91% of patients were free of gadolinium-enhancing lesions. Unadjusted annualized relapse rates were 0.31 (0.5 mg) and 0.18 (1.0 mg). 79% (0.5 mg) and 76% (1.0 mg) of patients experienced ≥1 treatment-emergent AE (TEAE), most commonly increased alanine aminotransferases, nasopharyngitis, and upper respiratory tract infection. 12 (0.5 mg) and 9 (1.0 mg) patients reported a serious TEAE. 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, ALT levels were ≥3x ULN in 6% (0.5 mg) and 7% (1.0 mg) of patients. 2% (0.5 mg) and <1% (1.0 mg) of patients discontinued ozanimod due to increased liver transaminases. Between baseline and week 120, 3 patients (1.0 mg) had absolute lymphocyte count (ALC) <200 cells/µL; none was associated with severe or serious infection. There were no notable cases of pulmonary TEAEs and no cases of macular edema, malignancy-related TEAEs, or serious opportunistic infections.
Conclusions: Both ozanimod doses demonstrated durable efficacy, with a favorable safety profile in patients continuing ozanimod for 120 weeks or switching from placebo to ozanimod for 96 weeks. These data support the ongoing RADIANCE (NCT02047734) and SUNBEAM (NCT02294058) phase 3 studies.