SMA Collaborative Program Initiates Phase 2 Studies of Potential Therapy

A spinal muscular atrophy (SMA) collaboration has two Phase 2 clinical trials aligned to evaluate the safety, tolerability, and effectiveness of the investigational drug RG7916 in pediatric and adult patients of Type 2 and Type 3 SMA and in pediatric patients of Type 1 SMA.

The SMA development program between PTC Therapeutics, Roche, and the SMA Foundation was launched in 2006 to accelerate the development of treatments for SMA.

The program is currently leading efforts in the development of RG7916, an oral small molecule SMN2 (survival motor neuron 2) modifier that directly targets the underlying molecular deficiency of SMA.

Results from a healthy volunteer study (NCT02633709) show that RG7916 increased the production of full-length SMN2 mRNA, demonstrating evidence of RG7916’s mechanism as an oral small molecule SMN2 modifier. The study also showed that RG7916 was well tolerated by participants.

The program will now focus on the Phase 2 SUNFISH (NCT02908685) trial, assessing RG7916 in Type 2 and Type 3 SMA patients, and in coming months will initiate the Phase 2 FIREFISH (NCT02913482) clinical trial, assessing RG7916 in pediatric Type 1 SMA patients.

SUNFISH is a two-part study evaluating RG7916; the first part will evaluate the safety and tolerability of the drug candidate through escalating doses. Once the correct dose is selected, the study will transition to the second part, scheduled for 2017, to evaluate RG7916’s effectiveness compared to a placebo.

SUNFISH is expected to enroll 36 Type 2 and Type 3 pediatric and adult patients for at least 12 weeks in its first part, and about 150 Type 2 and Type 3 SMA patients for up to 24 months for the second part, followed by an open-label extension study.

A similar two-part study evaluating RG7916 in Type 1 SMA, FIREFISH, is also expected to begin in early 2017. FIREFISH will evaluate RG7916 in at least eight pediatric patients for at last four weeks. The objective of the study is to assess the safety profile of the investigative drug in infants to determine the dose for part two. The second part will assess the drug’s tolerability of the selected dose in about 40 pediatric patients for 24 months, also followed by an open-label extension study.

“We are excited to initiate clinical studies in SMA patients with RG7916 and advance our spinal muscular atrophy program forward,” Stuart W. Peltz, PhD, PTC Therapeutics’ CEO, said in a press release.

“An oral small molecule splicing modifier has the potential benefit of systemic exposure to promote SMN protein in all affected organs and tissues. This attribute, along with an ease of administration, provides promise for this program to have a meaningful benefit for SMA patients.”