Roche Stops Work on Olesoxime After Disappointing Long-term Results in Phase 2 Trial

Roche has stopped the development of olesoxime, a treatment candidate for spinal muscular atrophy (SMA) following disappointing 18-month results in an ongoing clinical study, the company announced.

In a statement shared online through TreatSMA, Roche mentioned the most recent results of the OLEOS Phase 2 trial (NCT02628743), an open-label study in Europe on the long-term safety, tolerability, and efficacy of olesoxime in type 2 and non-ambulatory type 3 SMA patients.

Despite positive results at 12 months of treatment, analysis at 18 months showed deterioration of motor function. Roche presented these findings at the 2018 American Academy of Neurology (AAN) Annual Meeting, recently held in Los Angeles.

Olesoxime is an oral compound intended to protect motor neurons, specialized nerve cells connecting the central nervous system with muscles and glands.

The therapy’s development presented other challenges to Roche as well. These include its formulation, optimal dosage and requests from the U.S. Food and Drug Administration and the European Medicines Agency to run a new Phase 3 trial, which the company hoped to start later this year.

With the emergence of an effective SMA treatment (Spinraza) requirements for how effective a new medication needs to be are now more demanding, which impacts the design and conduction of clinical studies, Roche noted in its statement.

The company said it had “many discussions” with the regulatory agencies and SMA experts, worked to improve olesoxime’s formulation and dose, and tried to design the best Phase 3 trial possible to assess the investigational therapy’s efficacy.

“We understand the urgency of finding solutions for the SMA community and we have always tried to overcome the difficulties with olesoxime,” Sangeeta Jethwa, MD, head of Patient Partnership, Rare Diseases, wrote.

However, “based on all of the available evidence and the continued difficulties described above, we have decided to stop further development of olesoxime,” she added.

While reaffirming Roche’s disappointment with the news, Jethwa added that the company’s top priority is to ensure that patients in the OLEOS trial understand what this decision means for them and that they have access to appropriate treatments.

In this regard, Roche is “working closely” with trial sites and investigators to identify patients taking part in the study and will keep it open to make sure all participants have a confirmed treatment alternative.

Roche is continuing to advance its SMA program, which includes RG7916, a treatment candidate that modifies the splicing (editing) of premature RNA molecules to increase the production of full-length SMN, the protein lacking in SMA patients.

RG7916, a once-daily liquid solution, is being developed with Genentech and in collaboration PTC Therapeutics and the SMA Foundation.

Current studies of RG7916 include the FIREFISH Phase 2/3 trial (NCT02913482) in babies with type 1 SMA, as well as and the SUNFISH Phase 2/3 study (NCT02908685) and the JEWELFISH Phase 2 study (NCT03032172) in types 2 and 3.

All three trials are recruiting participants.

Jethwa ended her statement by acknowledging the “tremendous contribution” of the families who have participated in the olesoxime studies and “the entire SMA patient community who inspire us on a daily basis.”