Risdiplam Gets Priority Review for Spinal Muscular Atrophy


The FDA set a PDUFA date for risdiplam of May 24, 2020. The full 12-month data from the SUNFISH trial are expected to be presented at an upcoming medical meeting.

Dr Stuart Peltz

Stuart W. Peltz, PhD, chief executive officer, PTC Therapeutics

Stuart W. Peltz, PhD

The FDA has granted a priority review designation for the new drug application (NDA) for risdiplam, also known as RG7916, an investigational and orally active small molecule therapy for the treatment of spinal muscular atrophy (SMA), according to an announcement from PTC Therapeutics.1

Risdiplam’s Prescription Drug User Fee Act (PDUFA) date has been set for May 24, 2020. The NDA is supported by 12-month data from the dose-finding phases of the pivotal trials SUNFISH and FIREFISH, as well as preclinical and clinical pharmacokinetic and pharmacodynamic data.

"The FDA's acceptance of the NDA is an important step towards making risdiplam available to SMA patients in the US," Stuart W. Peltz, PhD, chief executive officer, PTC Therapeutics, said in a statement. "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," Peltz added.

FIREFISH is an open-label, 2-part clinical trial of risdiplam in infants with SMA type 1, while SUNFISH is a double-blind, 2-part, placebo-controlled trial in patients with type 2 or 3 SMA aged 2 to 25 years. PTC noted in its announcement that the results from SUNFISH part 2, which recently met its primary end point of change in the Motor Function Measure 32 (MFM-32) scale, will be presented at an upcoming medical congress.

The interim analysis of SUNFISH part 2 included data from 180 non-ambulant patients with type 2 or 3 SMA; the study assessed safety and efficacy as measured by change in the MFM-32 scale of the risdiplam dose level selected from part 1 for 24 months. The dose-finding portion of part 1 included 51 patients and evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of several risdiplam dose levels.2

After 12 months of treatment, the study met its primary endpoint of change from baseline in MFM-32 compared with placebo. The study affirmed the consistent safety profile of risdiplam from previous trials. No patients experienced any treatment-related safety issues, and there was high tolerability among patients assessed. Notably, no patients withdrew from the study for safety-related issues.

In March, NeurologyLive spoke with John W. Day, MD, PhD, professor of neurology, pediatrics, and pathology at Stanford University Medical Center, who has been involved in the clinical development of risdiplam as well as other investigational therapies for SMA, to learn more about the possible advantages of the PTC agent. He offered some insight into a pair of benefits that give the therapy a leg-up on others.

“It’s definitely easier to use than the only commercially available product, which at this point is nusinursen (Spinraza, Biogen) which would have to be administered intravitally. So that’s one of its advantages,” Day explained. “The second potential advantage is that, because it’s orally administered, it’s a systematic administration. What we really still don’t know is what aspects of SMA might be related to the loss of SMN protein production in cells other than the central nervous system.”

Notably, the filing acceptance by the FDA triggers a $15M milestone payable to PTC by Roche. This SMA development program is a collaboration between PTC, the SMA Foundation, and Roche.


1. PTC Therapeutics Announces FDA Grants Priority Review to Risdiplam for the Treatment of Spinal Muscular Atrophy [press release]. South Planfield, NJ: PTC Therapeutics; Published November 25, 2019. prnewswire.com/news-releases/ptc-therapeutics-announces-fda-grants-priority-review-to-risdiplam-for-the-treatment-of-spinal-muscular-atrophy-300964301.html. Accessed November 25, 2019.

2. Genentech’s Risdiplam Meets Primary Endpoint in Pivotal SUNFISH Trial In People With Type 2 or 3 Spinal Muscular Atrophy [news release]. San Francisco, CA: Genentech. November 10, 2019. businesswire.com/news/home/20191110005058/en/Genentech’s-Risdiplam-Meets-Primary-Endpoint-Pivotal-SUNFISH. Accessed: November 25, 2019.

Related Videos
Michael Levy, MD, PhD
Michael Kaplitt, MD, PhD
Michael Kaplitt, MD, PhD
video 4 - "Amyloid Cascade Hypothesis of Alzheimer’s Disease"
Video 3 - "Amyloid Precursor Protein and Amyloid Beta Species in Alzheimer’s Disease"
Svetlana Blitshteyn, MD, FAAN, director and founder of Dysautonomia Clinic
© 2024 MJH Life Sciences

All rights reserved.