A Long-Term, Open-Label Follow-Up Study of Olesoxime in Patients with Type 2 or Non-Ambulatory Type 3 Spinal Muscular Atrophy who Participated in a Placebo-Controlled Phase 2 Trial (S46.002)

Objective: OLEOS (NCT02628743) is an open-label extension study assessing the long-term safety and efficacy of olesoxime in patients with Type 2 or non-ambulatory Type 3 spinal muscular atrophy (SMA). Background: Olesoxime is an oral, daily administered compound that supports the function of mitochondria. In a previous randomized, double-blind Phase 2 study (NCT01302600) in patients aged 3–25 years with Type 2 or non-ambulatory Type 3 SMA, olesoxime maintained motor function over 24 months, whilst the placebo group declined. Design/Methods: One hundred and twenty-nine patients with Type 2 or non-ambulatory Type 3 SMA from the previous Phase 2 study were enrolled and treated with olesoxime (10 mg/kg); the majority have been followed for 12 months (n=104). Primary endpoint is safety and secondary endpoints include change in Motor Function Measure (MFM) D1+D2 from baseline up to 5 years. OLEOS baseline visit occurred 2.4–5.1 years (median 3 years) after study drug discontinuation in Phase 2. Results: Consistent with previous studies, olesoxime was generally safe and well tolerated at the dose assessed. Maintenance of motor function observed over 2 years in the Phase 2 study was followed by a substantial decline in MFM D1+D2 (u003e2 points/year) after drug discontinuation. However, the ~2-point MFM treatment difference between olesoxime and placebo at the end of Phase 2 was maintained at OLEOS baseline. Furthermore, olesoxime open-label treatment stabilized motor function (mean change in MFM D1 + D2 from baseline: 6 months, −0.03 [SD, 4.79; n=124]; 12 months, −0.22 [SD, 4.74, n=104]). These data support the long-term stabilization of motor function observed in the Phase 2 study. A study update including novel 18-month data will be presented. Conclusions: These data suggest that olesoxime offers the potential to provide meaningful clinical benefit and may play a role in the future therapeutic management of SMA. Study Supported by: Sponsored by F. Hoffmann-La Roche Disclosure: Dr. Muntoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Participation to SAB meetings (Roche; Avexis and Biogen) and educational activities (Biogen). Dr. Muntoni has received research support from My institute receives support for Biogen and Roche sponsored clinical trials. Dr. Buchbjerg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Bertini has nothing to disclose. Dr. Dessaud has nothing to disclose. Dr. Mercuri has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen MA, Inc, Ionis Pharmaceuticals, Inc. u0026 F. Hoffman La-Roche Ltd. Dr. Kirschner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Roche, Avexis. Dr. Kirschner has received research support from Biogen, Roche, Santhera, PTC. Dr. Reid has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche Products Ltd (employee). Dr. Lusakowska has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC, Roche. Dr. Comi has nothing to disclose. Dr. Cuisset has nothing to disclose. Dr. Abitbol has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Inventiva Pharma. Dr. Abitbol holds stock and/or stock options in Pfizer. Dr. Scherrer has received personal compensation in an editorial capacity for Trophos SA. Dr. Morawski Vianna has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-LaRoche. Dr. Van Der Pol has nothing to disclose. Dr. Vuillerot has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Biogen. Dr. Vuillerot has received research support from Roche. Dr. Gorni has nothing to disclose. Dr. Fontoura has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann La-Roche Ltd. Dr. Fontoura holds stock and/or stock options in F. Hoffmann La-Roche Ltd., which sponsored research in which Dr. Fontoura was involved as an investigator.