Oral Ozanimod Efficacy and Safety Results at 2 Years from Phase 2 RADIANCE Trial of Patients with Relapsing Multiple Sclerosis Presented at 32nd ECTRIMS
BOUDRY, Switzerland--(BUSINESS WIRE) September 16, 2016 -- Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation (NASDAQ:CELG), today announced results from the 96-week blinded extension period (for a total of up to 120 weeks of exposure on treatment) of the RADIANCE phase 2 trial of ozanimod, an investigational oral, selective S1P 1 and 5 receptor modulator, in patients with relapsing multiple sclerosis (RMS). The results were presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), which is being held in London from September 14-17, 2016.
"The data from this blinded extension are encouraging and further support evaluation of the benefit-risk profile of ozanimod in the ongoing phase 3 trials of patients with relapsing multiple sclerosis," said Giancarlo Comi, MD, Professor of Neurology, Chairman of the Department of Neurology, and Director of the Institute of Experimental Neurology, at Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan.
As previously announced at ECTRIMS 2014, 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 blinded extension period 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). The extension week 96 visit was completed by 224 of the patients (90 percent) who entered the extension study.
At extension week 96, the mean number of GdE lesions was 0.3 for patients on the 0.5 mg dose and 0.1 for the 1 mg dose, compared with 0.4 and 0.1, respectively, at week 48. The proportion of patients who were free of GdE lesions was 91 percent for the 0.5 mg dose and 89 percent for the 1 mg dose. The cumulative number of new or enlarging T2-hyperintense lesions was 1.8 for the 0.5 mg dose and 0.6 for the 1 mg dose, compared with 1.3 and 0.7, respectively, at week 48.
The effect on unadjusted annualized relapse rate (uARR) was maintained in both ozanimod dose groups with uARR of 0.30 for the 0.5 mg dose and 0.19 for the 1 mg dose at extension week 96, and 0.26 and 0.15, respectively, at week 48.
No evidence of disease activity (NEDA: no GdE or new/enlarging T2 lesions, and no relapse or increase in Expanded Disability Status Scale [EDSS]) was achieved in 44 percent and 39 percent of patients at extension week 48 and 96, respectively, on the 0.5 mg dose and 62 percent and 47 percent on the 1 mg dose.
Reported treatment-emergent adverse events (AEs) were comparable across ozanimod dose groups; the most common reported AEs during the blinded extension (weeks 24 to 96) were minor infections (nasopharyngitis, respiratory tract and urinary tract) and headache. Alanine aminotransferase at least three times the upper limit of normal was reported in 11 patients (4.4 percent) through extension week 96. Consistent with extension week 48 data, no noteworthy occurrences of cardiac, pulmonary, serious opportunistic infections, ophthalmologic, or malignancy-related TEAEs were observed. No first-dose TEAEs of bradycardia of AV block ≥ 2nd degree were reported from day 1 of the study or day 1 of the extension.
"These 2-year safety and efficacy results further underscore the potential of ozanimod to offer a new oral therapeutic option for patients with this chronic condition. Based on these findings, and as part of our commitment to bringing innovative medicines to this patient community, we look forward to the continued study of this compound in the two ongoing pivotal phase 3 clinical trials in RMS," said Scott Smith, President, Celgene Inflammation & Immunology.
The phase 2 portion of RADIANCE is a randomized, double-blind, placebo controlled 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 55 sites in 13 countries, which was followed by a 2-year blinded extension period where all patients received ozanimod. The primary endpoint of the placebo-controlled 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 relapsing multiple sclerosis. 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.
Ozanimod is a novel, oral, selective, sphingosine 1-phosphate 1 (S1PR1) and 5 (S1PR5) 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 T and B lymphocytes that leads to anti-inflammatory activity by inhibiting migration of specific 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 International Sàrl, located in Boudry, Switzerland, is a wholly-owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit www.celgene.com.
This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made. Celgene Corporation undertakes no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond Celgene's control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in Celgene's Annual Report on Form 10-K and other reports filed with the U.S. Securities and Exchange Commission.
Source: Celgene International Sàrl
Posted: September 2016
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