Risdiplam Decision Delayed Pending New SMA Data Review


The FDA has moved the PDUFA date for risdiplam back to August 24, 2020, as the agency works to review additional data that was made available from part 2 of the pivotal SUNFISH trial.

Stuart W. Peltz, PhD

Stuart W. Peltz, PhD

The regulatory decision for the investigational spinal muscular atrophy (SMA) treatment risdiplam (Roche/Genentech) has been pushed back by several months as the FDA reviews new data, according to an announcement from Roche.1

The drug, an orally active survival motor neuron-2 (SMN2) splicing modifier potentially effective for the treatment of all types of SMA, had an original PDUFA date of May 24, 2020. The new PDUFA date is now August 24, 2020.

"We are encouraged that the FDA has no substantive review issues. Their interest in the additional results from the clinical studies demonstrating risdiplam's activity supports our goal of enabling access to this important therapy for all SMA patients," said Stuart W. Peltz, PhD, Chief Executive Officer, PTC Therapeutics, who co-developed the drug alongside Roche.2 "Enabling access to a home-administered oral therapy for a broad patient population is critically important and we look forward to the FDA living up to its commitment to review the application as quickly as possible."

The delay is the result of Roche submitting additional data from the pivotal SUNFISH part 2 trial (NCT02908685), which demonstrated the drug’s efficacy in patients aged 2 to 25 with SMA types 2 or 3.

Those findings, which were presented at the 2nd International Scientific and Clinical Congress on Spinal Muscular Atrophy, February 5-7, 2020 in Evry, France,3 showed that patients treated with risdiplam had a significantly greater change in Total Motor Function Measure 32 (MFM-32) compared with placebo (1.55 mean point difference; P =.0156). In addition, patients treated with the study drug also showed an improvement in Revised Upper Limb Module, a key secondary end point of the trial (1.59 point difference; P =.0028).

WATCH: SMA Cure Connections: The Importance of Treating SMA Early

The strongest response to treatment based on change in MFM-32 versus placebo was recorded in patients in the youngest age group (2-5 years; 78.1% vs 52.9% achieving ≥3 point increase), while patients age 18 to 25 showed disease stabilization (57.1% vs 37.5%, with stabilization defined as a ≥0 point increase), which is considered a goal of treatment in populations with more advanced disease.3

Earlier this year, Roche/Genentech and PTC Therapeutics also announced results from the pivotal, phase 2/3 FIREFISH study (NCT02913482) which included infants age 1 to 7 months with SMA type 1.4 The study met its primary end point, with a significant proportion of patients sitting without support for at least 5 seconds after 1 year of treatment.

“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.”

Two additional phase 2 trials are ongoing, JEWELFISH (NCT03032172) and RAINBOWFISH (NCT03779334), which will assess treatment in patients previously treated with other SMA drugs, including nusinersen and Zolgensma, as well as infants who have been genetically diagnosed with SMA but are asymptomatic.


1. Roche provides regulatory update on risdiplam for the treatment of spinal muscular atrophy (SMA) [news release]. Basel, Switzerland: Roche. April 7, 2020. Accessed April 7, 2020. globenewswire.com/news-release/2020/04/07/2013141/0/en/Roche-provides-regulatory-update-on-risdiplam-for-the-treatment-of-spinal-muscular-atrophy-SMA.html

2. PTC Announces Regulatory Update on Risdiplam for Spinal Muscular Atrophy (SMA) [news release]. South Plainfield, NJ: PTC Therapeutics. April 7, 2020. Accessed April 7, 2020. prnewswire.com/news-releases/ptc-announces-regulatory-update-on-risdiplam-for-spinal-muscular-atrophy-sma-301036990.html

3. Genentech’s Risdiplam Showed Significant Improvement in Motor Function in People Aged 2-25 With Type 2 or 3 Spinal Muscular Atrophy [news release]. South San Francisco, CA: Genentech. February 6, 2020. Accessed April 7, 2020. gene.com/media/press-releases/14836/2020-02-06/genentechs-risdiplam-showed-significant-

4. 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. Accessed April 7, 2020. biospace.com/article/releases/genentech-s-risdiplam-meets-primary-endpoint-in-pivotal-firefish-trial-in-infants-with-type-1-spinal-muscular-atrophy.

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