Oral Ozanimod 72-week Phase II outcomes from RADIANCE Trial
New Jersey based Biopharmaceutical Company Celgene Corporation has reported 72-week outcomes from the RADIANCE phase II trial of ozanimod, an investigational selective S1P 1 and 5 receptor modulator, in sufferers with relapsing multiple sclerosis. The outcomes were provided at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). Full information of the 24-week study outcomes was also recently presented online in the Lancet Neurology.
As earlier announced, RADIANCE met its primary efficacy endpoint – decrease in the cumulative number of total gadolinium-enhancing (GdE) lesions, as identified by MRI, from week 12 to week 24. In the 48-week blinded extension portion of the research, sufferers actually randomized to ozanimod carried on their allocated dose (0.5 mg, n = 85; 1 mg, n = 81), while sufferers in the placebo arm were randomized to either dose of ozanimod (0.5 mg, n = 41; 1 mg, n = 42).
For individuals who obtained ozanimod consistently via week 72, the mean number of GdE lesions at week 72 was 0.4 for sufferers on the 0.5 mg dose and 0.2 for the 1 mg dose, similar to outcomes obtained at week 24. For placebo participants switched after week 24 to ozanimod 0.5 mg or 1 mg, the mean number of GdE lesions at week 72 was reduced by 89 and 95%, accordingly.
For participants who obtained ozanimod consistently via week 72, the proportion of sufferers who were free of GdE lesions at week 72 was 73 % for the 0.5 mg dose and 88 % for the 1 mg dose, in comparison with 84 % and 89 %, accordingly, at week 24. For those who switched from placebo to ozanimod, the corresponding ratios at week 72 were 85 % for the 0.5 mg dose and 79 % for the 1 mg dose, respectively, in comparison with 59 % and 69 %, respectively, at week 24.
A reduce in the unadjusted annualized relapse rate (uARR) between week 24 and week 72 was noticed for all therapy groups, with a larger effect for the 1 mg dose. For all those on ozanimod continuously via week 72, the decrease 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 outcomes were seen in the group moved from placebo to ozanimod after week 24.
Reported adverse events (AEs) were same across ozanimod dose groups; the most frequently reported non-laboratory therapy-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 lower than one beat per minute. Alanine aminotransferase at least 3 times the upper limit of normal was claimed in 3-4 % of subjects through week 72.
Scott Smith, President, Celgene Inflammation & Immunology said,
“These data recommend that ozanimod has the possible to offer a new oral therapeutic choice for sufferers with relapsing multiple sclerosis who seek treatments with various benefit-risk profiles to help manage their chronic condition”. “The 72-week safety and efficacy outcomes further show the potential promise of ozanimod. We look forward to the ongoing study of this substance in the two ongoing pivotal phase 3 clinical studies – SUNBEAM and the 2-year portion of the RADIANCE trial.”
The phase 2 portion of RADIANCE is a randomized, double-blind research evaluating the efficacy, safety and tolerability of two orally given doses (0.5 mg and 1 mg) of ozanimod against placebo in 258 subjects with RMS throughout 77 sites in 13 nations. The primary endpoint of the study is the decrease in the cumulative number of total GdE lesions identified by MRI from week 12 to week 24 of trial treatment, a standard endpoint for phase II studies 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 till week 24 and safety and tolerability, as assessed by the site investigator.
The 2-year phase 3 portion of RADIANCE was started under a Special Protocol Assessment with the US FDA in December 2013.
Ozanimod is a small molecule sphingosine 1-phosphate 1 and 5 receptor modulator in development for immune-inflammatory indications which includes relapsing multiple sclerosis and inflammatory bowel disease. Therapy with S1P receptor modulators is considered to work by interfering with S1P signaling and preventing the response of lymphocytes (a kind of white blood cell) to exit signals from the lymph nodes, sequestering them within the nodes. The outcome is a decrease in circulating lymphocytes that lead to anti-inflammatory action by inhibiting migration of pathologic lymphocytes to sites of inflammation.
Ozanimod is an investigational substance that is not accepted for any use in any country.