Roche's Evrysdi Makes History as First FDA-Approved Pill for Spinal Muscular Atrophy

In a groundbreaking development for patients with spinal muscular atrophy (SMA), the U.S. Food and Drug Administration (FDA) has approved Roche's Evrysdi as the first-ever tablet treatment for the condition. This milestone approval, granted to Roche subsidiary Genentech, marks a significant advancement in SMA therapy, offering patients a more convenient and flexible dosing option.

A New Era in SMA Treatment

Evrysdi (risdiplam) is now the only noninvasive disease-modifying therapy available for SMA patients. The tablet formulation, which can be taken whole orally or dissolved in water, is expected to be available in the coming weeks. It is approved for patients aged 2 years and older who weigh more than 20 kg (44 lbs).

Dr. Levi Garraway, Genentech's chief medical officer, hailed the approval as a "significant step forward" for SMA patients. "Evrysdi has robust potential to modify the SMA disease trajectory, and has already been used to treat thousands of patients to date," Garraway stated, emphasizing that the tablet formulation "combines established efficacy with convenience."

Mechanism of Action and Clinical Efficacy

Evrysdi's active ingredient, risdiplam, is a small-molecule drug that promotes the production of full-length and functional SMN protein in the brain. The survival of motor neuron (SMN) protein plays a crucial role in repairing DNA, managing cellular stress, and preserving overall neuromuscular function. In SMA patients, genes encoding for SMN are typically mutated, leading to dysfunctional protein expression.

The FDA's approval of the tablet form was supported by data from a bioequivalence study. Results demonstrated that a 5-mg tablet could elicit comparable exposure to risdiplam as the oral solution, suggesting that patients taking the tablet will experience "the same established efficacy and safety" as those using the liquid formulation.

Competitive Landscape and Future Outlook

Evrysdi's approval as a tablet comes at a time of significant activity in the SMA treatment space. Biogen recently announced that the FDA had accepted a supplemental filing for Spinraza, proposing a higher dose of the Ionis-partnered asset for SMA. Additionally, Scholar Rock reported successful Phase III testing for its myostatin blocker apitegromab in October, showing significant improvements in motor function in children with SMA.

While this approval represents a major win for Roche in the neurodegenerative disease arena, the company has faced setbacks in other areas. In December 2024, Roche's Parkinson's disease candidate prasinezumab, developed in partnership with Prothena, failed its Phase IIb trial. The company also relinquished rights to an Alzheimer's disease prospect, bepranemab, returning them to UCB in October 2024.

As the pharmaceutical industry continues to innovate in the treatment of rare and debilitating conditions, Evrysdi's tablet formulation stands as a testament to the ongoing efforts to improve patient care and quality of life for those living with SMA.