SMA Newsroom

• First placebo-controlled trial to include adults with SMA demonstrates risdiplam improved or stabilised motor function
• Medically meaningful and statistically significant results in primary and key secondary endpoints
• Pivotal SUNFISH Part 2 study population represents broad, real-world spectrum of people living with SMA

At our 2nd International Scientific and Clinical Congress on Spinal Muscular Atrophy in Evry, France today, 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 SMA. The study showed that change from baseline in the primary endpoint of the Motor Function Measure 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.

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 stabilisation was observed in the 18-25 years age group (57.1% vs 37.5%, with stabilisation defined as a ≥0 point increase), which is the goal of treatment for those with more established disease.

“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, M.D., Ph.D., Department of Paediatric 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.”

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%), diarrhoea (16.7%), vomiting (14.2%) and cough (14.2%). While the rate of lower respiratory tract infections overall was similar in both treatment arms (RIS 19%, PLB 20%), serious lower respiratory tract infections occurred in more patients in the risdiplam group (RIS 10% PLB 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.

“We are very encouraged by the positive results in this broad group of SMA patients, many of whom are under-served and under-represented in clinical trials,” said Levi Garraway, M.D., Ph. D., Roche’s Chief Medical Officer and Head of Global Product Development. “This study has helped us understand which measurement scales are the most relevant for patients, as well as the importance of stabilisation in people with more established disease.”

Roche leads the clinical development of risdiplam, an investigational, orally administered survival motor neuron-2 (SMN2) 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 programme 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 U.S Food and Drug Administration granted Priority Review for risdiplam with a decision for approval by May 24, 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 through to use of hands and fingers.

**RULM 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.