Genentech Considering Design of Phase 3 Clinical Trial for SMA Therapy

Genentech is working on the design of a Phase 3 clinical trial of olesoxime to address U.S. and European regulators’ concerns about the benefits versus the risks of the spinal muscular atrophy (SMA) therapy.

Meanwhile, two Phase 2 trials of another Genentech SMA treatment, RG7916, are under way.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) asked for the Phase 3 trial of olesoxime. Genentech, a subsidiary of Roche, wants to design a study that takes their concerns into account.

Olesoxime is aimed at maintaining the functioning of mitochondria, cell components that convert food to energy. Impairment of that function is associated with SMA, scientists believe.

RG7916 is an SMN2 splicing modifier that enhances the production of the SMN2 protein. That protein plays a key role in maintaining motor neurons in the spinal cord and part of the brain. SMA is characterized by loss of motor neurons and progressive muscle wasting.

The FDA has given Orphan Drug Designation to RG7916. Genentech is collaborating with PTC Therapeutics and the SMA Foundation on the therapy’s development.

The Phase 2 SUNFISH (NCT02908685) and FIREFISH (NCT02913482) clinical trials will be investigating the safety, tolerability, and properties of RG7916.

SUNFISH will cover children and young adults — ages 2 to 25 — with type 2 or 3 SMA. Researchers  said it is a randomized, placebo-controlled, and double blind study.

Participants are being randomly assigned to either a treatment group or a placebo group who will constitute a control. Neither researchers nor patients will know which group a participant belongs to.

The low-dose stage of the trial is complete. Researchers administered RG7916 to 10 adults and adolescents — Group A — and nine children — Group B. The research team is in the midst of enrolling patients for a higher-dose stage.

The FIREFISH trial is enrolling infants between 1 and 7 months old with Type 1 SMA. The study will be open label, meaning there will be no placebo group. The first infant received RG7916 in December of 2016.

The JEWELFISH trial will assess the safety and tolerability of RG7916 in SMA patients who have already received an SMN2-targeting therapy. A previous clinical trial involving the same category of patients was terminated due to unexpected toxicity. That trial (NCT02240355) was called MOONFISH.

JEWELFISH, which is expected to last two years, has dosed its first patient in the United States.

If you’re interested in participating in a trial, contact your physician or visit this link.