Tuesday, Oct 11, 2022
New two-year Evrysdi data show improvement or maintenance of motor function in people with SMA, a progressive neuromuscular disease that can be fatal
The JEWELFISH study enrolled the broadest and most diverse patient population ever studied in an SMA trial
Longer-term safety data consistent with that previously seen in earlier trials and low study drop-out rate
Evrysdi has proven efficacy in babies, children and adults, with more than 7,000 patients treated to date worldwide
South San Francisco, CA -- October 11, 2022 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new two-year data from the JEWELFISH study evaluating Evrysdi® (risdiplam) in people with Type 1, 2 or 3 SMA aged 6 months to 60 years at time of enrollment. Patients had been previously treated with other approved or investigational SMA-targeting therapies, including nusinersen (Spinraza®) or onasemnogene abeparvovec (Zolgensma®). Data showed Evrysdi improved or maintained motor function and led to rapid increases in SMN protein levels which were sustained after two years of treatment. These data will be presented at the 27th World Muscle Society (WMS) congress, October 11-15, 2022.
“The consistent safety profile and exploratory efficacy we have seen in the JEWELFISH study, the largest ever conducted in previously treated patients, reinforces Evrysdi as a meaningful treatment option across SMA populations,” said Dr. Claudia Chiriboga, Professor of Neurology and Pediatrics, Department of Neurology, Columbia University Medical Center, New York. “The findings add to our confidence when making treatment decisions for previously-treated patients in need.”
The JEWELFISH study enrolled the broadest and most diverse patient population ever studied in an SMA trial. Of the 174 people enrolled, 36% (n=63) were adults, 63% (n=105) had a Hammersmith Functional Motor Scale Expanded (HFMSE) score of less than 10 at baseline, meaning their disease was very severe, and 83% (n=139) had scoliosis. Forty-four percent (n=76) of those enrolled had previously been treated with nusinersen (Spinraza), 41% (n=71) with olesoxime*, 8% (n=14) with onasemnogene abeparvovec (Zolgensma) and 7% (n=13) with RG7800*.
People with SMA are unable to produce enough survival motor neuron (SMN) protein, leading to debilitating and potentially fatal muscle weakness. The study showed Evrysdi led to a two-fold increase in median SMN protein levels versus baseline after four weeks of treatment in all patient groups, irrespective of previous treatment. The SMN protein levels achieved after four weeks of treatment were maintained for over two years.
Observed through exploratory efficacy endpoints, the study also suggests maintenance of motor function was sustained at two years of treatment as measured by change from baseline in Motor Function Measure 32 (MFM-32), Revised Upper Limb Module (RULM) and HFMSE total scores compared to the natural history of SMA in untreated patients. A recent survey conducted by patient advocacy group SMA Europe showed that more than 96% of people with SMA viewed disease stabilization as progress in terms of their expectations of treatment.
“These important data demonstrate the safety and efficacy of Evrysdi in a broad, real-world population of people previously treated with an SMA-targeting therapy,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Those enrolled in JEWELFISH had very severe disease, with over 80% having scoliosis, so maintaining motor function–especially for a progressive disease–can be potentially life-changing.”
The overall adverse event (AE) and serious adverse event (SAE) profiles observed with Evrysdi treatment in JEWELFISH were reflective of underlying disease. The rate of AEs decreased by more than 50% between the first and second six-month period, and then remained stable thereafter. The rate of SAEs, including pneumonia, decreased throughout the 24-month period, with a total reduction of more than 50% by the second year. The most common AEs (reported in ≥12% of all patients; n=173) were pyrexia (24%), upper respiratory tract infection (21%), headache (18%), nasopharyngitis (16%), diarrhea (14%), nausea (13%) and cough (12%). The most common SAEs (reported in >2% of all patients) were pneumonia (3%), respiratory failure (2%), respiratory distress (2%), lower respiratory tract infection (2%) and upper respiratory tract infection (2%). The most common AEs/SAEs were consistent with those observed in treatment-naïve patients in our other three trials. Low rates of discontinuation from the study were observed, with a 5% rate per year over the 24-month period.
Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.
*RG7800 and olesoxime are no longer in development as investigational treatments for patients with 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 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 the 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 91 countries and the dossier is under review in a further 18 countries.
Evrysdi is currently being evaluated in five multicenter trials in people with 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.
What is Evrysdi?
Evrysdi is a prescription medicine used to treat spinal muscular atrophy (SMA) in children and adults.
Important Safety Information
These are not all of the possible side effects of Evrysdi. For more information on the risk and benefits profile of Evrysdi, ask your healthcare provider or pharmacist.
You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.
Please see 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.
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