Despite Favorable Safety, Olesoxime Falls Short Among Efficacy Markers for SMA

Long-term follow-up of the treatment showed that while it has a favorable safety profile, the treatment does not offer significant efficacy for patients with spinal muscular atrophy (SMA) type 2 and non-ambulant type 3.

While it may be a safe option for the treatment of spinal muscular atrophy (SMA), olesoxime lacks the efficacy needed for meaningful improvements in motor function for these patients, according to long-term follow-up of the treatment.

On the one hand, the long-term follow-up of patients with type 2 and non-ambulant type 3 SMA is adding to the safety profile of olesoxime, which has previously demonstrated favorable safety in a phase 2 trial, finding no new safety risks.

Throughout the OLEAS, there were no patient deaths and the majority of adverse events were classified as mild or moderate. The treatment was tolerable, with 1 patient discontinuing treatment prematurely because of non-serious asthenia and paresthesia. The most common adverse events of any grade included upper respiratory tract infection (29.0%), nasopharyngitis (22.9%), pyrexia (21.4%), vomiting (18.3%), and headache (17.6%).

On the other hand, the open-label extension study (OLEOS)—an extension of the phase 2 and a phase 1b study—found no indication that the treatment offers significant benefit in these patients, with no stabilization of functional measures observed over 130 weeks.

In the initial phase 2 study, olesoxime did not meet the primary endpoint, although secondary endpoints and sensitivity analyses of the study indicated that the treatment may be beneficial in maintaining motor function in these types of patients.

However, these new results did not confirm the previous findings. Among the 131 patients included in the long-term follow-up, there were small, nonsignificant changes in motor function over 52 weeks, after which scores declined for the remainder of the study follow-up. Between week 52 and week 130, there was a 4.02-point mean decrease in total motor function measure, and there was a near 5-point decrease in D1+D2 score, which measured standing position, transfers, and ambulation, as well as axial and proximal motor function.

The decline was most prominent among patients aged 15 years or younger, as well as among patients with type 2 SMA.

“There was no clear evidence that olesoxime provides significantly better efficacy than natural history after 12 months,” concluded the researchers, based on the findings, which also showed that FVC also declined throughout the follow-up. They added, “It is therefore difficult to determine a position for olesoxime in the SMA treatment landscape alongside recently approved SMN-upregulating treatments such as nusinersen, onasemnogene abeparvovec and risdiplam, which have dramatically altered the natural history of SMA.”

All patients received 10 mg/kg oral olesoxime once daily until November 2017 when 21 patients began receiving the treatment twice daily based on the previous phase 2 trial showing improvements in motor function after 2 years in patients with higher treatment exposure. However, the researchers found no differences in efficacy associated with the higher dose. They also noted that the small number of patients receiving the treatment twice daily was insufficient to draw a conclusion about the comparative safety of the higher dose.


Muntoni F, Bertini E, Comi G, et al. Long-term follow-up of patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA) treated with olesoxime in the OLEOS trial. Neuromuscular disord. Published online November 4, 2020. doi:10.1016/j.nmd.2020.10.008