New Data for Genentech’s Evrysdi (risdiplam) Demonstrate Long-Term Efficacy and Safety in a Broad Population of People With Spinal Muscular Atrophy (SMA)
- Category: Small Molecules
- Published on Wednesday, 16 March 2022 09:20
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Long-term efficacy data from the pivotal SUNFISH study confirm increases in motor function are sustained at three years while adverse events decreased over the same period
Part 2 of SUNFISH showed Evrysdi demonstrated a marked improvement in, or stabilization of, motor function after two years compared to an untreated external control group
Latest interim results from the RAINBOWFISH study demonstrate that the majority of babies treated with Evrysdi for at least 12 months were able to stand and walk within timeframes typical of healthy babies
More than 5,000 patients have been treated with Evrysdi to date, from newborns to people over 60 years of age
SOUTH SAN FRANCISCO, CA, USA I March 15, 2022 I Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new data for Evrysdi® (risdiplam) in spinal muscular atrophy (SMA). Presentations included new three-year data from the SUNFISH study which further confirmed the long-term efficacy and safety of Evrysdi in a broad population of people aged 2-25 years with Type 2 or Type 3 SMA. Additional presentations included exploratory two-year efficacy data from SUNFISH Part 2, demonstrating improvement in, or stabilization of, motor function with Evrysdi compared to an untreated external control group. Genentech also announced updated interim data from the RAINBOWFISH study in pre-symptomatic babies with SMA under two months of age. The data were presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, March 13-16, 2022.
“The positive long-term efficacy and safety results for Evrysdi in this broad SMA population are important for physicians as they consider Evrysdi as a treatment option for their patients,” said Laurent Servais, M.D., Ph.D., Professor of Paediatric Neuromuscular Diseases at the MDUK Oxford Neuromuscular Centre. “In treating people with SMA, our aim is to enable or preserve their independence and patients in the SUNFISH study reported continuous improvement or stabilization in the level of help needed for daily living.”
In the SUNFISH study, the increase in Motor Function Measure 32 (MFM-32) total score from baseline previously observed at year one was maintained through year three in people treated with Evrysdi. The increases in Revised Upper Limb Module (RULM) and Hammersmith Functional Motor Scale Expanded (HFMSE) total scores from baseline were also sustained between year one and year three.
Evrysdi was well-tolerated over the three-year time period in the SUNFISH study. The overall rate of adverse events (AEs) in SUNFISH decreased over three years, and a trend towards a lower rate of serious adverse events (SAEs) was observed in the third year of treatment. Overall, AEs and SAEs were reflective of the underlying disease and no treatment-related AEs led to withdrawal from the study.
In addition, for the first time, an external comparator analysis has been done for SUNFISH two-year data with an untreated control group.
The weighted exploratory analyses of MFM total scores showed that in SUNFISH Part 2, the proportion of patients demonstrating a marked improvement (change ≥3 points) or stabilization (change ≥0 points) were more likely in patients who were on Evrysdi for 24 months than those in the untreated comparator group (p=0.025 and p=0.002 respectively).
“We are pleased that these long-term results further reinforce the safety and efficacy of Evrysdi and it is especially encouraging to see that adverse events decreased over time,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “We remain committed to working towards continued access to Evrysdi for all appropriate patients with this progressive disease.”
Updated interim data from the RAINBOWFISH study were also shared, demonstrating the safety and efficacy of Evrysdi for newborns. In January, the U.S. Food and Drug Administration (FDA) granted priority review of a supplemental new drug application (sNDA) for the use of Evrysdi to treat pre-symptomatic babies under two months of age with SMA.
To date, more than 5,000 people have been treated with Evrysdi in clinical trials, compassionate use or real-world settings. Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.
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 as demonstrated in animal models. 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 76 countries and the dossier is under review in a further 29 countries.
Evrysdi is currently being evaluated in five multicenter 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 Evrysdi in infants and determining the dose for Part 2. Part 2 is a pivotal, single-arm study of Evrysdi in 41 infants with Type 1 SMA treated for two years, followed by an open-label extension. Enrollment 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 (PK) and pharmacodynamics (PD) in people with SMA aged six 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, multicenter study, investigating the efficacy, safety, PK and PD of Evrysdi 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 (RO7204239), 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 commencing recruitment in Q1 2022.
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.
What is Evrysdi?
Evrysdi is a prescription medicine used to treat spinal muscular atrophy (SMA) in adults and children 2 months of age and older.
Please see the full Prescribing Information for additional Important Safety Information.
About Genentech in Neuroscience
Neuroscience is a major focus of research and development at Genentech. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases.
Genentech and Roche are 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.
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.