SMA THERAPIES II AND BIOMARKERS: P.260A long-term, open-label, follow-up study of olesoxime in patients with type 2 or non-ambulatory type 3 SMA who participated in a placebo-controlled phase 2 trial

Abstract

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 spinal muscular atrophy (SMA), olesoxime maintained motor function over 24 months, whilst the placebo group declined. OLEOS (NCT02628743) is an open-label extension of the phase 2 study assessing the long-term safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 SMA. 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). The primary endpoint is safety and secondary endpoints include change in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) from baseline to 5 years. The OLEOS baseline visit occurred 2.4-5.1 years after study drug discontinuation in phase 2. 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 (>2 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. Olesoxime open-label treatment stabilized motor function up to 12 months (mean change in MFM D1 + D2 from baseline: 6 months, -0.03 [n=124]; 12 months, -0.22 [n=104]). From 12-18 months, motor function appears to decline gradually, with large variability observed. A study update, including novel 18-month data, will be presented. These data suggest that olesoxime offers the potential to provide meaningful clinical benefit to patients with SMA by preventing loss of motor function, and may play a role in the future therapeutic management of SMA.