Data from the pivotal Part 2 of the SUNFISH trial evaluating the safety and efficacy of risdiplam (Genentech) in adult and pediatric patients with Type 2 or Type 3 spinal muscular atrophy (SMA) were presented at the 2nd International Scientific and Clinical Congress on Spinal Muscular Atrophy in Evry, France.

Risdiplam is an investigational, orally administered liquid survival motor neuron-2 (SMN2) splicing modifier designed to increase and sustain SMN protein levels throughout the central nervous system and peripheral tissues of the body.

The SUNFISH study is a 2 part, multicenter, randomized, double-blind, placebo-controlled phase 2/3 trial in patients aged 2-25 years with Types 2 or 3 SMA (N=231). Part 2 of the study evaluated motor function in patients (n=180) for 24 months, with a primary end point of change from baseline using total score of Motor Function Measure 32 (MFM-32) at 12 months. 

Results showed that patients treated with risdiplam achieved a significantly greater change from baseline in the primary end point at month 12 compared with placebo (1.55 point mean difference; P =.0156). Risdiplam was also associated with a statistically significant improvement from baseline in the Revised Upper Limb Module, a key secondary end point designed to assess upper limb movement in patients with SMA (1.59 point difference; P =.0028). 

The strongest responses in MFM-32 were observed in patients aged 2-5 years, with 78.1% of patients achieving a ≥3 point increase compared with 52.9% of placebo-treated patients. Furthermore, disease stabilization (defined as a ≥0 point increase) was observed in 57.1% of patients aged 18-25 years treated with risdiplam compared with 37.5% of those who received placebo.

The safety profile of risdiplam was consistent with that seen in previous studies and no treatment-related adverse events were identified leading to study withdrawal. The adverse event profile was similar to placebo. The most common adverse events were upper respiratory tract infection (31.7%), nasopharyngitis (25.8%), pyrexia (20.8%), headache (20%), diarrhea (16.7%), vomiting (14.2%) and cough (14.2%).

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“Risdiplam is the first potential treatment to have pivotal placebo-controlled data in a broad population of patients, including children, teenagers and adults,” said SUNFISH principal investigator Eugenio Mercuri, MD, PhD, Department of Pediatric Neurology, Catholic University, Rome, Italy. “The data suggest that risdiplam can preserve and potentially enable greater independence through improved motor function in people with Type 2 or non-ambulant Type 3 SMA.”

In November 2019, the Food and Drug Administration (FDA) granted Priority Review to the New Drug Application (NDA) for risdiplam for the treatment of SMA. A Prescription Drug User Fee Act (PDUFA) target date of May 24, 2020 has been set for the application.

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