Results of a Phase 1b study to confirm safety and tolerability of olesoxime in multiple sclerosis patients (P7.282)

OBJECTIVE: to evaluate safety and tolerance of olesoxime administered with interferon-beta in RRMS patients. BACKGROUND: Olesoxime is an orally bioavailable, neuroprotective compound that stimulates myelination and myelin repair in preclinical models. Clinically, olesoxime prevents motor function decline for two years in spinal muscular atrophy patients. Current immunomodulatory therapies, although effectively controlling relapses, have little effect on long term disability in MS patients, which results from remyelination failure and neurodegeneration. Olesoxime could be a useful therapy to address this need in both RRMS and progressive MS. DESIGN/METHODS: A phase 1b study was conducted in three sites in France. Forty-four stable RRMS patients treated with interferon-beta were randomized to receive 495 mg olesoxime or matching placebo (22 per arm) for 24 weeks. The primary endpoint was the cumulative incidence of adverse events and secondary endpoint was MS activity assessed by MRI: the number of Gd-enhancing T1-lesions and the number of new or enlarged T2-lesions at 12 and 24 weeks compared to baseline. Multicenter MRI data was also processed to assess feasibility of whole brain atrophy, diffusion tensor imaging (DTI), magnetization transfer ratio (MTR) and 23Na-MRI (monocentric study) for use as biomarkers of myelination status and neurodegeneration/neuroprotection. RESULTS: Demographics and baseline MS parameters were not different between the olesoxime and placebo groups. At the end of the observation period there was no statistically significant difference between treatment arms in terms of AEs/SAEs, change in EDSS score, relapses, Gd-T1-lesions, new/enlarged T2-lesions or T2-lesion load. There were also no significant differences between groups in other exploratory MRI endpoints in this small, 6-month study; however, brain parenchymal fraction, 23Na-MRI and DTI appear to be sensitive measures of disease progression even during this short time period. CONCLUSIONS: Olesoxime is safe and well tolerated when co-administered with interferon beta. Supported by ANR-RPIB-0005-01 for the Translate MS-Repair project. Disclosure: Dr. PELLETIER has nothing to disclose. Dr. Ranjeva has nothing to disclose. Dr. Tourbah has received personal compensation for activities with Biogen Idec, Genzyme Corporation, Novartis, Merck Serono, and Teva Neuroscience. Dr. Edan has received personal compensation for activities with LFB, Biogenidec, speaking from Serono, Inc., Sanofi, Teva, and Bayer Pharmaceuticals Corporation as a consultant and/or scientific advisory board member. Dr. Barillot has nothing to disclose. Dr. Le La Mer has received personal compensation for activities with Trophos as an employee. Dr. Audoin has nothing to disclose. Dr. Rico Lamy has nothing to disclose. Dr. Crespy has nothing to disclose. Dr. Ridley has nothing to disclose. Dr. Zaaraoui has nothing to disclose. Dr. Confort-Gouny has nothing to disclose. Dr. Guye has nothing to disclose. Dr. Maarouf has nothing to disclose. Dr. Caucheteux has nothing to disclose. Dr. Chaunu has nothing to disclose. Dr. Portefaix has nothing to disclose. Dr. Pierot has received personal compensation for activities with Codman Neuro, eV3, MicroVention, Penumbra, Inc. and Sequent Scientific Limited. Dr. Commowick has nothing to disclose. Dr. Kerbrat has nothing to disclose. Dr. Catanese has nothing to disclose. Dr. Cuvier has received personal compensation for activities with Trophos as an employee. Dr. Veys has received personal compensation for activities with Trophos. Dr. Pruss has received personal compensation for activities with Trophos. Dr. Hauke has received personal compensation for activities with Trophos.