Rare Daily Staff

PTC Therapeutics said the U.S. Food and Drug Administration has granted Priority review for risdiplam, its experimental treatment for spinal muscular atrophy, with is exclusively licensed to Roche and its U.S. subsidiary Genentech.

Priority Review is granted to therapies the FDA determines have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The designation is intended to shorten the FDA review period to six months from the standard ten months, with a decision expected by May 24, 2020.

Spinal muscular dystrophy (SMA) is a rare genetic disease caused by a mutation in the SMN1 gene, which encodes the protein critical for the maintenance and function of specialized nerve cells called motor neurons. If there is not enough functional SMN protein, then the motor neurons die, leading to debilitating and often fatal muscle weakness. It is the most common genetic cause of infant mortality and one of the most common rare diseases, affecting approximately one in 11,000 babies.

There are five types of SMA. Infantile-onset, or SMA type 1, is the most severe and most common subtype of SMA, accounting for 50 to 70 percent of cases. The onset of SMA type 2 occurs in children between the ages of 7 months and 18 months. Symptoms of SMA type 3 usually occur after 18 months and may not appear until early adulthood.

“The FDA’s acceptance of the NDA is an important step towards making risdiplam available to SMA patients in the U.S.,” said Stuart Peltz, CEO of PTC Therapeutics. “We are proud that risdiplam, the first oral small molecule targeting splicing, was produced from our proprietary splicing platform.”

Risdiplam’s NDA submission includes results from a broad SMA patient population, including type 1, type 2 and type 3 SMA patients demonstrating improvements in motor functions and developmental milestones, and a compelling safety profile.


“We believe that an oral therapeutic that reaches all affected tissues in the body would mark a significant advancement in the treatment for SMA patients and their families,” said Stuart Peltz, CEO of PTC Therapeutics.

Risdiplam is designed to provide sustained increase in SMN protein centrally and peripherally through daily dosing and is being evaluated for its potential ability to help the SMN2 gene produce more functional SMN protein throughout the body.

The NDA filing is based on 12-month data from the dose-finding portion of the pivotal FIREFISH and SUNFISH studies, and clinical and preclinical pharmacokinetic and pharmacodynamic data. FIREFISH is an open-label, two-part clinical trial of risdiplam in infants with SMA type 1. SUNFISH is a double-blind, two-part, placebo-controlled trial of risdiplam in patients with type 2 or 3 SMA aged 2-25 years. SUNFISH part 2 recently met its primary endpoint of change from baseline in the Motor Function Measure 32 scale.

The risdiplam development program is a collaboration between PTC, the SMA Foundation and Roche. The filing acceptance by the FDA triggers a $15M milestone payable to PTC by Roche. It also puts Roche into good standing with rivals’ approved therapies for SMA: Novartis’ gene therapy Zolgensma and Biogen’s Spinraza.

Photo: Stuart Peltz, CEO of PTC Therapeutics.

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