Celgene Corporation has announced 72-week results from the RADIANCE phase 2 trial of ozanimod, an investigational selective S1P 1 and 5 receptor modulator, in patients with relapsing multiple sclerosis. The results were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) in New Orleans, Louisiana. Full details of the 24-week study results were also recently published online in the Lancet Neurology.
As previously announced, RADIANCE met its primary efficacy endpoint - reduction in the cumulative number of total gadolinium-enhancing (GdE) lesions, as determined by MRI, from week 12 to week 24. In the 48-week blinded extension portion of the study, patients originally randomized to ozanimod continued their assigned dose (0.5 mg, n = 85; 1 mg, n = 81), while patients in the placebo arm were randomized to either dose of ozanimod (0.5 mg, n = 41; 1 mg, n = 42).
For patients who received ozanimod continuously through week 72, the mean number of GdE lesions at week 72 was 0.4 for patients on the 0.5 mg dose and 0.2 for the 1 mg dose, similar to results obtained at week 24. For placebo patients switched after week 24 to ozanimod 0.5 mg or 1 mg, the mean number of GdE lesions at week 72 was decreased by 89 and 95 percent, respectively.
For patients who received ozanimod continuously through week 72, the proportion of patients who were free of GdE lesions at week 72 was 73 percent for the 0.5 mg dose and 88 percent for the 1 mg dose, compared with 84 percent and 89 percent, respectively, at week 24. For those who switched from placebo to ozanimod, the corresponding proportions at week 72 were 85 percent for the 0.5 mg dose and 79 percent for the 1 mg dose, respectively, compared with 59 percent and 69 percent, respectively, at week 24.
A decrease in the unadjusted annualized relapse rate (uARR) between week 24 and week 72 was observed for all treatment groups, with a larger effect for the 1 mg dose. For those on ozanimod continuously through week 72, the reduction in uARR was 0.43 for the 0.5 mg dose and 0.24 for the 1 mg dose at week 24, and 0.27 and 0.15, respectively, at week 72. Comparable results were seen in the group switched from placebo to ozanimod after week 24.
Reported adverse events (AEs) were similar across ozanimod dose groups; the most commonly reported non-laboratory treatment-emergent AEs were minor infections (nasopharyngitis, upper respiratory tract and urinary tract), back pain and headache. Maximum first-dose reductions from baseline in mean hourly heart rate were less than one beat per minute. Alanine aminotransferase at least three times the upper limit of normal was reported in 3-4 percent of patients through week 72.
"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," said Scott Smith, President, 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 the RADIANCE trial."
The phase 2 portion of RADIANCE 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 against placebo in 258 patients with RMS across 77 sites in 13 countries. The primary endpoint of the trial is the reduction in the cumulative number of total GdE lesions determined by MRI from week 12 to week 24 of study treatment, a standard endpoint for phase 2 trials in this indication. The secondary endpoints of the trial were: the number of GdE at week 24, the cumulative number of new or enlarging T2-hyperintense lesions at weeks 12-24, the annualized relapse rate from baseline until week 24 and safety and tolerability, as judged by the site investigator.
The 2-year phase 3 portion of RADIANCE was initiated under a Special Protocol Assessment with the U.S. Food and Drug Administration in December 2013.
Ozanimod is a small molecule sphingosine 1-phosphate 1 and 5 receptor modulator in development for immune-inflammatory indications including relapsing multiple sclerosis and inflammatory bowel disease. 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, sequestering them within the nodes. The result is a reduction of circulating lymphocytes that leads to anti-inflammatory activity by inhibiting migration of pathologic lymphocytes to sites of inflammation.
Ozanimod is an investigational compound that is not approved for any use in any country.