FDA Approves Tablet Formulation of Risdiplam for Spinal Muscular Atrophy

Levi Garraway, MD, PhD

The FDA has approved a new tablet formulation for risdiplam (Evrysdi; Genentech), one of the few authorized therapies to treat patients with spinal muscular atrophy (SMA), according to a company announcement. With the approval, it becomes the first and only tablet available to this patient population, who often face challenges with digesting and taking medication.¹

The new tablet, which comes in a 5-mg dose to be swallowed whole or dispersed in water, is expected to be available in the coming weeks. Similar to its existing prescribing information, the tablet is applicable for those with the disease aged 2 years or older who weigh more than 44 lbs. Risdiplam, a survival motor neuron 2 (SMN2) pre-mRNA splicing modifier, was originally approved in 2020 as a liquid oral solution, becoming the second approved agent for SMA.

The approval of the new tablet formulation was supported by results from a bioequivalence study, which showed that the 5-mg tablet—taken whole or dissolved in unchlorinated drinking water—provides similar exposure to risdiplam as the original oral solution. This is aimed at ensuring that patients can expect the same proven efficacy and safety as the oral solution.

"Evrysdi has robust potential to modify the SMA disease trajectory and has already been used to treat thousands of patients to date. This approval marks another significant step forward," Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a statement.¹ "The Evrysdi tablet combines established efficacy with convenience, providing an additional flexible option for SMA management."

As a SMN2 splicing modifier, risdiplam works by increasing the functional SMN protein from the SMN2 gene, which can partially compensate for the defective SMN1 gene seen in SMA. By enhancing the SMN2 gene’s ability to produce functional SMN protein, risdiplam helps stabilize motor neurons, thereby improving muscle strength and function. The therapy has also been approved in several other regions, including the European Union and Japan, following similar positive results from clinical trials.

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Risdiplam is taken once daily, offering convenience compared with other SMA treatments requiring more frequent hospital visits. As part of the label extension, the prescribing information for the medication was updated to include guidance on tablet administration and storage.

"We cannot underestimate the value that comes with simplifying treatment administration and disease management for people who are living with SMA or those caring for them," Kenneth Hobby, president of Cure SMA, said in a statement.¹ "This new room temperature stable formulation option offers an additional choice that may more conveniently fit into daily living activities such as working, traveling, and education."

Risdiplam’s original approval in 2020 made it the first marketed therapy indicated for at-home oral administration in patients with SMA. The agency’s decision to approve the therapy was based on findings from 2 clinical trials, FIREFISH (NCT02913482) and SUNFISH (NCT02908685). In these studies, risdiplam-treated patients achieved key motor milestones, such as the ability to sit without support, preserved vital function, and improved survival without the need for permanent ventilation.²

Since its approval, risdiplam has been and continues to be studied in various settings. It is currently being tested in the phase 4 HINALEA 1 (NCT05861986) and HINALEA 2 (NCT05861999) studies, which test the effectiveness and safety of risdiplam in patients under 2 years of age who received the Zolgensma gene therapy either presymptomatically or post-symptomatically. Genentech is also currently recruiting for the phase 2 PUPFISH study (NCT05808764), an open-label study testing the pharmacokinetics and safety of risdiplam in babies with SMA who are younger than 20 days of age (at first dose).¹

REFERENCES
1. FDA Approves Genentech’s Evrysdi Tablet as First and Only Tablet for Spinal Muscular Atrophy (SMA). News release. Genentech. February 12, 2025. Accessed February 12, 2025. https://www.businesswire.com/news/home/20250210728175/en/FDA-Approves-Genentech%E2%80%99s-Evrysdi-Tablet-as-First-and-Only-Tablet-for-Spinal-Muscular-Atrophy-SMA
2. PTC Therapeutics Announces FDA Approval of Evrysdi™ (risdiplam) for the Treatment of Spinal Muscular Atrophy in Adults and Children 2 months and older. News release. Published August 7, 2020. Accessed February 12, 2025. https://finance.yahoo.com/news/ptc-therapeutics-announces-fda-approval-175400735.html