Preliminary data from the Phase 2 SUNFISH trial (NCT02908685) show PTC Therapeutics’ investigative drug RG7916 increases production of the SMN (survival motor neuron) protein in types 2 and 3 spinal muscular atrophy (SMA) patients.
The results were presented by PTC Therapeutics at the 22nd International World Muscle Society (WMS) Congress in St. Malo, France, Oct. 3-7.
SMN forms complexes with many other proteins and is found throughout the body, including in the central nervous system. SMN levels are decreased in SMA and are associated with motor neuron loss and muscle atrophy. SMA is the most prevalent genetic cause of mortality in infants and young children.
SUNFISH is a double-blind (both scientists and participants are unaware of which drug is being administered), two-part, placebo-controlled trial including patients with types 2 and 3 SMA.
Part 1 of the study assessed the safety, tolerability, effectiveness, and pharmacological profile of several doses of orally administered RG7916 in both ambulatory and non-ambulatory SMA patients.
Part 2 will include 150 non-ambulatory patients to determine the safety and effectiveness of the recommended dosage of RG7916 selected from Part 1. An open-label extension study will follow.
Five groups of patients received RG7916 for 28 days or longer in Part 1 of SUNFISH. A preliminary analysis showed an exposure-dependent increase in SMN protein, due to RG7916’s modulation of SMN2 gene splicing. All doses of RG7916 have been well-tolerated, with no drug-related safety issues leading to withdrawal from the study.
“We are excited to report that in SMA patients who are deficient in SMN protein, RG7916 treatment led up to a median 2.5-fold increase in SMN protein,” Stuart W. Peltz, PhD, the chief executive officer of PTC Therapeutics, said in a press release. “Increasing SMN protein levels throughout the body has the potential to impact every aspect of this disorder.”
“These results have allowed us to determine the dose for the pivotal phase of the SUNFISH trial to evaluate the efficacy and safety of RG7916 versus placebo,” Peltz said.
The development and production of RG7916 is part of a joint effort between PTC Therapeutics, Swiss multinational Roche, and the SMA Foundation, a nonprofit that funds basic, translational, and clinical research.
Earlier this year, RG7916 was granted orphan drug and fast track designation by the U.S. Food and Drug Administration for the treatment of patients with SMA.
Orphan drug status is granted to promising therapies for rare diseases affecting fewer than 200,000 people in the U.S. It qualifies the company developing the drug for various research incentives, including tax credits for clinical testing and exemption from a prescription drug user fee.
PTC Therapeutics created an SMA research program in 2006 in partnership with the SMA Foundation to pursue a therapy for the devastating disease. In November 2011, Roche obtained an exclusive worldwide license to the PTC/SMA Foundation program studying alternative splicing (synthesis of different protein variants from the same messenger RNA sequence) of the SMN2 gene.
Roche has been developing these compounds with oversight by a tri-partite steering committee formed by PTC, Roche, and the SMA Foundation.