PTC’s Spinal Muscular Atrophy Phase 1b/2a Trial Begins

PTC Therapeutics, Inc. announced that their collaborative program with Roche and the SMA Foundation (SMAF) for Spinal Muscular Atrophy (SMA) has begun its second phase with adult and children patients, as part of the Phase 1b/2a study.

The program is evaluating the safety and tolerability of an under-investigation drug – survival of motor neuron 2 (SMN2) gene splicing modifier (RG7800) – for a period of three months. The Phase 1 study determined the effect of single-ascending dosages in healthy volunteers, and proved to be safe and tolerable. Additionally, RG7800 impacted SMN2 splicing, leading to changes in the ratio of SMN2 full length to SMN2 mRNA lacking exon 7, in a dose-dependent effect. Therefore, RG7800 has the potential to be developed into a new therapeutic that can restore SMN protein levels in muscles and the nervous system.

Spinal Muscular Atrophy (SMA) is caused by mutations in the Smn1 gene that encodes SMN1 protein, a key protein for motor neuron survival. The lack of SMN protein leads to motor neuron dysfunction and death triggering subsequent generalized muscle atrophy. SMA is the leading cause of death in infants and currently there is no cure. In humans, an additional gene Smn2 is present, however, it differs in two nucleotides, in exons 7 and 8, and that by a process known as alternative splicing only produces a small amount of its coded protein is functional.

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Stuart Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics commented, “We are excited to initiate the next phase of this program and begin a trial in SMA patients with our partners. We believe that the encouraging clinical results and preclinical data from relevant disease models are promising indications that the orally administered small-molecule RG7800 has the potential to modify the splicing of the SMN2 gene and generate more full-length SMN mRNA in SMA patients. The advancement of this potential new treatment, which could represent the first orally available SMN2 splicing modifier for SMA, is a significant milestone for patients and their families.”