Relapsing MS Treatment Showing Efficacy in Phase 2 Extension Study, Celgene Reports at ACTRIMS 2016
Celgene Corporation announced the results from an extension study of the RADIANCE Phase 2 clinical trial evaluating ozanimod in patients with relapsing multiple sclerosis (MS). The results were also presented at the recent Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2016 in New Orleans, Louisiana.
Ozanimod is a small molecule sphingosine 1-phosphate (S1P) 1 and 5 receptor modulator being developed to treat immune-inflammatory diseases, including relapsing MS. Treatment with S1P receptor modulators is believed to work by interfering with S1P signaling and blocking the response of lymphocytes — a type of white blood cell — to exit signals from the lymph nodes, locking them inside the nodes. This process results in a reduction of circulating lymphocytes, and to anti-inflammatory action by inhibiting the migration of pathologic lymphocytes to inflammation sites.
The RADIANCE trial is a randomized, double-blind study assessing the efficacy, safety and tolerability of two orally administered doses (0.5 mg and 1 mg) of ozanimod compared to placebo in 258 patients with relapsing MS across 77 sites in 13 countries.
According to a press release, the trial’s primary endpoint was a reduction in the cumulative number of total gadolinium-enhancing (GdE) lesions in patients, determined by magnetic resonance imaging (MRI), from the week 12 to week 24, and has already been reported as successfully met. In the 48-week blinded extension study arm, patients who had been previously randomized to ozanimod continued their assigned dose (0.5 mg, n = 85, and 1 mg, n = 81), while placebo group patients were randomized to one of the ozanimod doses (0.5 mg, n = 41, and 1 mg, n = 42).
At week 72 in the extension, researchers found that 73 percent of the patients who received 0.5 mg of ozanimod continuously and 88 percent of patients receiving 1 mg continuously were free of GdE lesions, compared to 84 percent and 89 percent, respectively, at week 24. For patients who went from placebo to ozanimod, 85 percent receiving 0.5 mg and 79 percent receiving 1 mg were free of GdE lesions at week 72. At week 24, their numbers were 59 percent and 69 percent, respectively.
Week 72 saw similar results to week 24 in terms of the mean number of GdE lesions — 0.4 in patients on a continuous 0.5 mg dose of ozanimod, and 0.2 for those continuously receiving 1 mg. For patients switching from placebo to either ozanimod dose at week 24, the mean number of GdE lesions decreased by 90–95 percent at week 72.
The unadjusted annualized relapse rate (uARR) dropped in the two ozanimod dose groups but a wider effect was observed in the 1 mg dose group, researchers found. For patients who received ozanimod on a regular basis through week 72, the uARR reduction was 0.43 for 0.5 mg and 0.24 for 1 mg at week 24, followed by 0.27 and 0.15, respectively, at week 72.
Overall, the team found that reductions in brain lesions at week 24 were sustained, while relapses were progressively reduced by week 72 with continued ozanimod administration.
The 24-week study results were recently published online in the journal Lancet Neurology under the title, “Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial.”
During this blinded extension study, there were no identified safety or tolerability issues. The most frequently reported non-laboratory, treatment-emergent adverse effects were minor infections, specifically of the upper respiratory and urinary tract and nasopharyngitis, and back pain and headaches.
“These data suggest that ozanimod has the potential to offer a new oral therapeutic option for patients with relapsing multiple sclerosis who seek therapies with different benefit-risk profiles to help manage their chronic disease,” concluded Scott Smith, president of Celgene Inflammation & Immunology. “The 72-week safety and efficacy results further demonstrate the potential promise of ozanimod. We look forward to the continued study of this compound in the two ongoing pivotal phase 3 clinical trials — SUNBEAM and the 2-year portion of RADIANCE.”