- Reductions in brain lesions at week 24 were maintained while relapses were further reduced at week 72 with continuous ozanimod treatment
No new safety or tolerability issues were identified during this blinded extension
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 either dose of ozanimod, the mean number of GdE lesions was decreased by 90 to 95 percent compared with that at week 24.
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.
The unadjusted annualized relapse rate (uARR) was decreased in both ozanimod dose groups; a larger treatment effect was observed in the 1 mg dose group. 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 groups 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 RADIANCE.”
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 relapsing multiple sclerosis 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.
About Multiple Sclerosis
Multiple sclerosis is a disease in which the immune system attacks the protective myelin sheath that covers the nerves. The myelin damage disrupts communication between the brain and the rest of the body. Ultimately, the nerves themselves may deteriorate — a process that's currently irreversible. Signs and symptoms vary widely, depending on the amount of damage and the nerves affected. Some people with severe multiple sclerosis may lose the ability to walk independently, while others experience long periods of remission during which they develop no new symptoms. Multiple sclerosis affects 400,000 people in the U.S. and approximately 2.5 million people worldwide.
Relapsing multiple sclerosis is characterized by clearly defined attacks of worsening neurologic function. These attacks — often called relapses, flare-ups or exacerbations — are followed by partial or complete recovery periods (remissions), during which symptoms improve partially or completely, and there is no apparent progression of disease. Relapsing multiple sclerosis is the most common disease course at the time of diagnosis. Approximately 85 percent of people are initially diagnosed with relapsing multiple sclerosis, compared with 10-15 percent with progressive forms of the disease.
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, FaceBook and YouTube.
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