Genentech/Roche, presented 1-year data from the pivotal Part 2 of SUNFISH, a global placebo-controlled study evaluating risdiplam in people aged 2-25 years with Type 2 or 3 spinal muscular atrophy (SMA). The study showed that change from baseline in the primary endpoint of the Motor Function Measure 32 scale (MFM-32) was significantly greater in people treated with risdiplam, compared to placebo (1.55 point mean difference; p=0.0156). The **Revised Upper Limb Module (RULM), a key secondary endpoint, also showed an improvement (1.59 point difference; p=0.0028).
Safety for risdiplam in the SUNFISH study was consistent with its known safety profile. Data were presented at the 2nd International Scientific and Clinical Congress on Spinal Muscular Atrophy from February 5-7 in Evry, France.
As anticipated, exploratory subgroup analyses showed that the strongest responses in *MFM-32 versus placebo were observed in the youngest age group (2-5 years) (78.1% vs. 52.9% achieving ?3 point increase). Importantly, disease stabilization was observed in the 18-25 years age group (57.1% vs. 37.5%, with stabilization defined as a ?0 point increase), which is the goal of treatment for those with more established disease.
Safety for risdiplam in the SUNFISH study was consistent with its known safety profile and no new safety signals were identified. 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%). While the rate of lower respiratory tract infections overall was similar in both treatment arms (risdiplam 19%, placebo 20%), serious lower respiratory tract infections occurred in more patients in the risdiplam group (risdiplam 10%, placebo 2%) but were reported as unrelated and resolved without change to study treatment.
To date, more than 400 patients have been treated with risdiplam across all studies, with no treatment-related safety findings leading to study withdrawal in any risdiplam trial.
Genentech leads the clinical development of risdiplam, an investigational, orally administered survival motor neuron-2 (SMN-2) splicing modifier for SMA, as part of a collaboration with the SMA Foundation and PTC Therapeutics. Risdiplam is being studied in a broad clinical trial program in SMA, with patients ranging from birth to 60 years old, and includes patients previously treated with SMA-targeting therapies. The clinical trial population represents the broad, real-world spectrum of people living with this disease with the aim of ensuring access for all appropriate patients.In November 2019, the FDA granted Priority Review for risdiplam with an expected decision on approval by 24 May 2020. (*MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA. It assesses 32 different motor functions from standing and walking to the use of hands and fingers. **ULM is a scale designed to assess upper limb movement in people with SMA. It can capture progressive muscle weakness across the spectrum of the disease, reflective of the SUNFISH Part 2 study population.