Results of a Phase II Study to Assess Safety and Efficacy of Olesoxime (TRO19622) in 3- to 25-Year-Old Spinal Muscular Atrophy Patients

Background and Objectives: Olesoxime (TRO19622) was identified as a potential treatment of spinal muscular atrophy (SMA) based on its beneficial effects in multiple preclinical neurodegeneration models. Olesoxime promotes neuron survival, neurite outgrowth, recovery from nerve injury and accelerates myelination or remyelination in models of demyelinating diseases. Maintaining motor neuron architecture and survival is highly relevant to SMA, a disease associated with progressive motor neuron compromise mainly affecting neuromuscular function. A clinical study has been performed to evaluate the effects of olesoxime treatment in patients with SMA. Results: A total of 165 type 2 or nonambulant type 3 SMA patients, aged 3 to 25 years were enrolled from 22 sites in seven European countries starting in November 2010. Patients were randomized to olesoxime, 10 mg/kg, administered as a liquid oral formulation or matching placebo in a 2:1 ratio and treatment duration was for 104 weeks. The last patient completed the study in October 2013. The primary outcome measure was the change in motor function using the motor function measure scale. The secondary outcome measures included the Hammersmith Functional Motor Scale for SMA, electromyography, pulmonary function, and patient-reported outcomes as well as safety. Patients in the placebo arm of the study experienced a loss of motor function at a similar rate to that previously reported. 1 Conclusions: Results from this pivotal double blind placebo-controlled clinical trial provide clinical proof of concept of olesoxime’s neuroprotective effect that is sustained over 2 years. This combined with good tolerability of the treatment will be submitted for the registration of olesoxime as the first neuroprotection treatment for SMA. In addition, the collected data will provide a valuable source of longitudinal data for motor function and potential prognostic biomarkers in a broad range of SMA patients. Acknowledgments: AFM-Téléthon, SMA Foundation, families of SMA, and special thanks to all the investigators, patients, and their families who participated in the clinical trial. Reference References 1 Vuillerot C, Rippert P, Roch S, et al. Development and validation of a motor function classification in patients with with neuromuscular disease: The NM-Score. Ann Phys Rehabil Med 2013;56(9-10):673–686