Roche's Oral Therapy Risdiplam Meets Primary Endpoint in Phase 3 SUNFISH Trial for Type 2/3 Spinal Muscular Atrophy

Today, Genentech, a member of the Roche Group, announced that risdiplam, its oral SMN2 splicing modifier, significantly improved motor function in patients with type 2 or type 3 spinal muscular atrophy (SMA) in the pivotal Phase 3 SUNFISH trial. The press release noted that this trial demonstrated for the first time that treatment with risdiplam can improve motor function in adult SMA patients.

The root cause of Spinal Muscular Atrophy (SMA) lies in the deficiency or dysfunction of a protein known as Survival Motor Neuron (SMN) protein. The SMN protein is crucial for maintaining the survival of motor neurons in the human body. There are two genes capable of producing the SMN protein: the SMN1 gene and the SMN2 gene. However, the SMN1 gene plays a dominant role, while the SMN2 gene produces only a small amount of SMN protein (approximately 10%). Therefore, once the SMN1 gene becomes dysfunctional, patients are unable to generate sufficient SMN protein, leading to the rapid death of motor neurons and progressive loss of muscle function. This ultimately results in paralysis and the inability to perform basic life-sustaining activities such as swallowing and breathing, posing a severe threat to the patient's life. Although SMA primarily manifests during infancy, it can affect individuals across any age range from infants to adults. Clinically, it is typically classified into three types: Type 1 (infantile), Type 2 (intermediate), and Type 3 (juvenile/adult-onset) SMA.

Risdiplam (RG7916) is an oral SMN2 gene splicing modifier jointly developed by Genentech, PTC Therapeutics, and the SMA Foundation. It modulates the splicing of SMN2 gene mRNA, thereby increasing the expression of SMN protein in the central nervous system (CNS) and peripheral tissues. This therapeutic strategy for SMA is highly similar to that of Spinraza, which has already been approved. The key difference lies in the fact that Spinraza utilizes antisense oligonucleotides (ASOs) to modulate RNA splicing and requires direct intrathecal injection into the cerebrospinal fluid, whereas risdiplam is a small-molecule drug administered orally. Clinical trial results have demonstrated that risdiplam exhibits superior efficacy in treating infants with Type 1 SMA. Currently, it is undergoing multipleClinical TrialTreatment of SMA patients aged 0 to 60 years.

In the Phase 3, double-blind, placebo-controlled trial named SUNFISHClinical TrialsIn the study, patients aged 2 to 25 years with type 2 and type 3 spinal muscular atrophy (SMA) received risdiplam treatment. Trial data demonstrated that after one year of treatment, patients in the treatment group achieved a statistically significant improvement from baseline in their Movement Function Measure-32 (MFM-32) scores compared to the placebo group, which constituted the primary endpoint of the trial. Additionally, assessment using the Revised Upper Limb Module (RULM) revealed improvements in this secondary endpoint among patients treated with risdiplam. Furthermore, it is noteworthy that a greater proportion of patients in the treatment subgroup aged 18 to 25 years experienced disease stabilization (57.1% vs. 37.5%). For patients with long-standing disease, stabilizing the condition is the primary goal.BioValley Bioon.com）