Roche's Oral Therapy Evrysdi Demonstrates Sustained Long-Term Efficacy and Safety in SMA Patients Across Broad Age Groups

Recently, Genentech, a subsidiary of Roche, announced new positive data on the oral therapy Evrysdi (risdiplam) for treating patients with spinal muscular atrophy (SMA). New three-year data from a Phase 2/3 clinical trial further demonstrated the long-term efficacy and safety of Evrysdi in a broad patient population aged 2-25 with Type 2 or Type 3 SMA. Additionally, exploratory two-year efficacy data from Part 2 of the trial showed that Evrysdi improved or stabilized motor function compared to the control group. Furthermore, Genentech announced updated interim data from a Phase 2 clinical trial conducted in pre-symptomatic SMA infants under two months of age, demonstrating the safety and efficacy of Evrysdi in this patient population.

SMA is a severe, progressive, and potentially fatal neuromuscular disease. It affects approximately one in ten thousand infants and is the leading genetic cause of infant mortality. While SMA primarily manifests during infancy and early childhood, patients can be affected at any age, from infancy to adulthood. SMA is caused by mutations in the SMN1 gene, which result in a deficiency of the survival motor neuron (SMN) protein. This protein is present throughout the body and is crucial for the function of muscles and motor neurons. Although the SMN2 gene in humans can also produce the SMN protein, mRNA splicing errors lead to very low levels of functional SMN protein, insufficient to compensate for the loss caused by SMN1 gene mutations.

Evrysdi is a small molecule mRNA splicing modifier targeting the SMN2 gene, jointly developed by Genentech and PTC Therapeutics. Evrysdi alleviates symptoms in SMA patients by modulating the splicing of SMN2 gene mRNA to increase levels of mRNA that can express functional SMN protein. Evrysdi is a liquid-formulated drug that can be administered orally at home or given through a feeding tube in liquid form. In 2017, the U.S. FDA granted Evrysdi orphan drug designation, and in August 2020, it approved the drug, making it the first oral therapy approved for treating SMA in infants aged two months and older, as well as adult SMA patients.

In the Phase 2/3 clinical trial named SUNFISH, the improvement in the total score of the Motor Function Measure-32 (MFM-32) observed in patients treated with Evrysdi after one year of treatment was still maintained in the third year. The increases from baseline in the Revised Upper Limb Module (RULM) and the Hammersmith Functional Motor Scale Expanded (HFMSE) total scores were also sustained between Year 1 and Year 3. Moreover, Evrysdi was well-tolerated over the three years of the trial, with the overall incidence of adverse events (AEs) decreasing over the three years, and a trend toward a reduction in the incidence of serious adverse events (SAEs) observed in the third year of treatment.

In addition, researchers conducted an external comparative analysis of the two-year data from this trial with a group of untreated patients for the first time. A weighted exploratory analysis of the MFM total score showed that in Part 2 of the trial, a higher proportion of patients who received Evrysdi treatment for 24 months achieved significant improvement (change ≥3 points) or stabilization (change ≥0 points) compared to the control group (p=0.025 and p=0.002, respectively).

Latest interim results from a Phase 2 clinical trial in SMA infants under two months of age who have not yet shown symptoms indicate that the majority of infants treated with Evrysdi for at least 12 months are able to stand and walk within the typical timeframe for healthy infants. In January this year, the FDA granted priority review status to Roche's supplemental New Drug Application (sNDA) for Evrysdi in treating these patients.

References:

[1] New Data for Genentech’s Evrysdi (risdiplam) Demonstrate Long-Term Efficacy and Safety in a Broad Population of People With Spinal Muscular Atrophy (SMA). Retrieved March 15, 2022, from https://www.gene.com/media/press-releases/14945/2022-03-15/new-data-for-genentechs-evrysdi-risdipla

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