Risdiplam Meets Primary End Point in SMA Type 1


Part 2 of the pivotal FIREFISH clinical trial met its primary end point in infants aged 1 to 7 months with Type 1 spinal muscular atrophy, with statistically significant and medically meaningful motor milestone improvements.

Dr Levi Garroway

Levi Garraway, MD, PhD, chief medical officer, and head, Global Product Development, Genentech

Levi Garraway, MD, PhD

Genentech announced that its pivotal, phase 2/3 FIREFISH study (NCT02913482) of risdiplam, also known as RG7916, for the treatment of type 1 spinal muscular atrophy (SMA) met its primary end point, with a significant proportion of infants sitting without support for at least 5 seconds after 1 year of treatment.1

The primary endpoint was change in Gross Motor Scale of the Bayley Scales of Infant and Toddler Development — Third Edition (BSID-III). Full results of the investigational survival motor neuron-2 (SMN-2) splicing modifier's impact, which was developed to improve SMN protein levels throughout the central nervous system (CNS) and in the periphery, are expected to be presented at an upcoming medical congress.

“This large, global trial confirms the efficacy of risdiplam in an advanced and difficult-to-treat population, including many infants whose disease had already progressed significantly before starting treatment,” said Levi Garraway, MD, PhD, chief medical officer, and head, Global Product Development, Genentech, in a statement. “We are very encouraged by these results and we look forward to sharing them with regulators. We also thank the entire SMA community for their continued partnership.”

WATCH NOW: Risdiplam: An Oral Treatment for Spinal Muscular Atrophy

In November 2019, the FDA granted a priority review designation for the investigational and orally active small molecule therapy. 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.

FIREFISH is a 2-part, open-label, pivotal study including infants aged 1 to 7 months with type 1 SMA. The first part included 21 patients and assessed the safety profile and determined the dose for part 2. This second phase included 41 patients, assessing efficacy. SUNFISH (NCT02908685) was also a 2-part, double-blind, placebo-controlled trial assessing the therapy in patients aged 2 to 25 years with type 2 or 3 SMA. Its first part included 51 patients to determine the dose for part 2, which included 180 patients who were assessed on motor function using the total score of Motor Function Measure 32 (MFM-32) at 12 months. Risdiplam also met its primary end point in SUNFISH.2,3

“It’s an oral medication given once a day that works in a very similar fashion as nusinersen does, in that it increases alternative slicing of the SMN2 gene so that more SMN is produced,” Claudia Chiriboga, MD, MPH, professor of neurology and pediatrics, Columbia University Medical Center in New York, told NeurologyLive recently. “A difference, other than that it’s administered orally, is that it also penetrates systemically. It goes uniformly into the CNS with a 1-to-1 penetration, at least in many species, including monkeys, so that blood levels are thought to reflect concentrations in the brain.”

In addition to SUNFISH and FIREFISH, 2 additional clinical trials—JEWELFISH and RAINBOWFISH—are still ongoing as they evaluate the efficacy of risdiplam in people with SMA.

JEWELFISH (NCT03032172) is an open-label exploratory trial in people with SMA type 1, 2 or 3 aged 6 months to 60 years who have been previously treated with SMA therapy, gene therapy, or olesoxime. RAINBOWFISH (NCT03779334), also open-label, is a single-arm, multicenter study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of risdiplam in babies with genetically diagnosed SMA who are not yet presenting symptoms. They will be assessed from birth to 6 weeks of age, at first dose. It is currently recruiting.


1. Genentech’s Risdiplam Meets Primary Endpoint in Pivotal FIREFISH Trial in Infants With Type 1 Spinal Muscular Atrophy [press release]. South San Francisco, CA: Genentech; Published January 23, 2020. biospace.com/article/releases/genentech-s-risdiplam-meets-primary-endpoint-in-pivotal-firefish-trial-in-infants-with-type-1-spinal-muscular-atrophy. Accessed January 23, 2020.

2. AveXis presented robust data at AAN demonstrating efficacy of Zolgensma in broad spectrum of spinal muscular atrophy (SMA) patients [news release]. Basel, Switzerland: AveXis; May 5, 2019. novartis.com/news/media-releases/avexis-presented-robust-data-aan-demonstrating-efficacy-zolgensma-broad-spectrum-spinal-muscular-atrophy-sma-patients. Accessed January 23, 2020.

3. PTC Therapeutics announces risdiplam (RG7916) is well tolerated at all dose levels with no drug-related safety findings [news release]. Dallas, TX: Cure SMA; June 19, 2018. www.curesma.org/news/ ptc-therapeutics-update-june2018.html. Accessed January 23, 2020.​​​​

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