PTC Therapeutics’ joint development program in spinal muscular atrophy (SMA) with Roche and the SMA Foundation (SMAF) has started a phase Ib/IIa study in adult and pediatric patients. The placebo-controlled, randomized, multiple-dose study will enroll approximately 48 patients with SMA and investigate the safety and tolerability of an investigational survival of motor neuron 2 (SMN2) gene splicing modifier (RG7800) over 12 weeks. The achievement of this milestone triggers a $10 million payment to PTC from Roche.

Stuart Peltz, Ph.D., CEO of PTC Therapeutics, said, "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."

The phase I, single-ascending dose study in healthy volunteers demonstrated that all doses studied were safe, well tolerated and demonstrated a dose-dependent effect on SMN2 splicing as shown by a change in the ratio of full-length SMN2 mRNA to SMN2 mRNA without exon 7 (SMND7), which is interpreted as proof-of-mechanism in terms of the expected pharmacodynamic effect.

SMA is caused by a missing or defective SMN1 gene, which results in reduced levels of SMN protein. This genetic neuromuscular disease is responsible for the loss of motor neurons within the spinal cord leading to muscle atrophy and death at infant age in its most severe form. The company believes the oral small molecule RG7800 may have the potential to target the underlying cause of the disorder by increasing SMN protein levels in the nervous system, muscles and other tissues. It is estimated that one in 10,000 children in the U.S. are born with this rare disorder.