Data from pivotal SUNFISH study showed increases in motor function observed during the first year were maintained through the fourth year, while the overall rate of adverse events continued to decrease

Data confirm long-term efficacy and safety profile of Evrysdi in a broad range of people with Type 2 and non‑ambulant Type 3 SMA

More than 8,500 people—from newborns to the over 60s—have been treated with Evrysdi, which is now approved in more than 90 countries worldwide

Basel, 20th March 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced new long-term data for Evrysdi® (risdiplam) in a broad range of people aged 2-25 years with spinal muscular atrophy (SMA) from the pivotal SUNFISH study1. Data confirm increases in motor function were sustained at four years and the overall rate of adverse events continued to decrease over the 48 month period, reinforcing the long-term efficacy and safety of Evrysdi. Participants also reported continuous improvement or stabilisation when independently performing activities of daily living such as eating, drinking and picking up and moving objects. The data were presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, March 19-22, 2023.

“Preserving long-term independence and the ability to perform daily tasks is an important measure for people living with SMA and their caregivers. It’s encouraging to see that Evrysdi has meaningfully affected this aspect of their lives,” said Laurent Servais, M.D., Ph.D., Professor of Paediatric Neuromuscular Diseases at the MDUK Oxford Neuromuscular Centre. “This trial included people with Type 2 and 3 SMA, including patients with advanced disease. These latest data make us confident that the improvement observed during the first year of treatment is sustained during four years which contrasts with the decline we would observe in the absence of treatment.”

The increase in motor function from baseline observed during the first year of the study was maintained through the fourth year of treatment with Evrysdi, as measured by changes in Motor Function Measure 32 (MFM-32) and Revised Upper Limb Module (RULM). Without treatment, natural history data show that patients with Type 2 or 3 SMA typically show a decline in motor function over time. Evrysdi was well-tolerated over the four-year time period. Adverse events (AEs) and serious adverse events (SAEs) were reflective of the underlying disease. The most commonly reported AEs include headache, fever (pyrexia) and upper respiratory tract infection. No treatment-related AEs led to withdrawal from the study.

“These new data show that treatment with Evrysdi may help people with Type 2 or 3 SMA to maintain improvements in muscle strength and mobility over the course of several years,” said Levi Garraway, M.D., Ph. D., Chief Medical Officer and Head of Global Product Development. “The longer-term results of this study add to the robust body of findings from our broad clinical trial programme evaluating Evrysdi across a variety of ages, disease severities and treatment histories.”

In addition to bringing Evrysdi to people around the world, Roche also leads its clinical development as part of a collaboration with the SMA Foundation and PTC Therapeutics. Roche is currently investigating Evrysdi in combination with an anti-myostatin molecule targeting muscle growth in the Ph II/III trial Manatee for the treatment of SMA.

About Evrysdi® (risdiplam)

Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron (SMN) protein deficiency. Evrysdi is administered daily at home in liquid form by mouth or by feeding tube.

Evrysdi is designed to treat SMA by increasing and sustaining the production of SMN protein in the central nervous system (CNS) and peripheral tissues. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.

Evrysdi was granted PRIME designation by the European Medicines Agency (EMA) in 2018 and Orphan Drug Designation by the U.S. Food and Drug Administration in 2017. In 2021, Evrysdi was awarded Drug Discovery of the Year by the British Pharmacological Society as well as the Society for Medicines Research award for Drug Discovery. Evrysdi is currently approved in more than 90 countries and the dossier is under review in a further 16 countries.

Evrysdi is currently being evaluated in five multicentre trials in people with SMA:

FIREFISH (NCT02913482) – an open-label, two-part pivotal clinical trial in infants with Type 1 SMA. Part 1 was a dose-escalation study in 21 infants with the primary objective of assessing the safety profile of risdiplam in infants and determining the dose for Part 2. Part 2 is a pivotal, single-arm study of risdiplam in 41 infants with Type 1 SMA treated for 2 years, followed by an open-label extension. Enrolment for Part 2 was completed in November 2018. The primary objective of Part 2 was to assess efficacy as measured by the proportion of infants sitting without support after 12 months of treatment, as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) (defined as sitting without support for 5 seconds). The study met its primary endpoint.

SUNFISH (NCT02908685) – SUNFISH is a two-part, double-blind, placebo-controlled pivotal study in people aged 2-25 years with Types 2 or 3 SMA. Part 1 (n=51) determined the dose for the confirmatory Part 2. Part 2 (n=180) evaluated motor function using the total score of Motor Function Measure 32 (MFM-32) at 12 months. MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA. The study met its primary endpoint.

JEWELFISH (NCT03032172) – an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in people with SMA aged 6 months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi. The study has completed recruitment (n=174).

RAINBOWFISH (NCT03779334) – an open-label, single-arm, multicentre study, investigating the efficacy, safety, pharmacokinetics, and pharmacodynamics of risdiplam in babies (~n=25), from birth to six weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is fully enrolled.

MANATEE (NCT05115110) – a global phase 2/3 clinical study to evaluate the safety and efficacy of GYM329 (RG6237), an anti-myostatin molecule targeting muscle growth, in combination with Evrysdi for the treatment of SMA in patients 2-10 years of age. The FDA Office of Orphan Products Development granted GYM329 Orphan Drug Designation for the treatment of patients with SMA in December 2021. The study is currently recruiting.

About SMA

SMA is a severe, progressive neuromuscular disease that can be fatal. It affects approximately one in 10,000 babies and is the leading genetic cause of infant mortality. SMA is caused by a mutation of the survival motor neuron 1 (SMN1) gene, which leads to a deficiency of SMN protein. This protein is found throughout the body and is essential to the function of nerves that control muscles and movement. Without it, nerve cells cannot function correctly, leading to muscle weakness over time. Depending on the type of SMA, an individual’s physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.

About Roche in Neuroscience

Neuroscience is a major focus of research and development at Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases.

Roche is investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today.

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the twelfth consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan