Thursday, Jun 10, 2021
Data from JEWELFISH, the first trial in a diverse population aged 1 to 60
years with SMA who received prior treatment, showed a consistent safety
profile and >2-fold increase in SMN protein levels
Pre-symptomatic babies with SMA treated with Evrysdi for at least one year
were able to sit, stand and walk in preliminary data from RAINBOWFISH study
Evrysdi has proven efficacy in adults, children and babies 2 months and older and is now approved in 44 countries worldwide
South San Francisco, CA -- June 10, 2021 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new interim data from two studies of Evrysdi® (risdiplam); JEWELFISH and RAINBOWFISH. Data from JEWELFISH, an ongoing open-label study primarily evaluating the safety of Evrysdi in people aged 1 to 60 years who have been previously treated with another SMA-targeting therapy, including nusinersen and onasemnogene abeparvovec, showed the safety profile of Evrysdi and increase in SMN protein levels are consistent with those observed in other Evrysdi studies.
Interim exploratory efficacy data from JEWELFISH also suggest stabilization in motor function at one year of treatment as measured by change from baseline in motor function measure (MFM-32). A recent survey from SMA Europe showed that almost 97% of people living with SMA reported disease stabilization as progress.
Preliminary efficacy data from RAINBOWFISH, an ongoing open-label study evaluating Evrysdi in babies from birth to 6 weeks with pre-symptomatic SMA, showed that infants treated for 12 months achieved age-appropriate motor milestones, including sitting, standing and walking, and improvements in motor function. These data will be presented at the 2021 Virtual SMA Research & Clinical Care Meeting from June 9-11, 2021.
“These data from JEWELFISH add to the growing body of evidence supporting the use of Evrysdi in patients from 1 to 60 years of age,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Moreover, the early findings from RAINBOWFISH in presymptomatic babies under two months old are very encouraging. Altogether, we are hopeful that Evrysdi will continue to help address unmet treatment needs of the diverse SMA community.”
The JEWELFISH study enrolled the broadest patient population ever studied in an SMA trial, including patients with SMA Types 1-3 who received prior treatment across a wide range of ages and disease severities. Of the 174 people enrolled, 30% were teenagers and 35% adults, 62% had a HFMSE* score of less than 10 at baseline, 80% had scoliosis and 47% had undergone scoliosis surgery. Seventy-six people had previously been treated with nusinersen and 14 with onasemnogene abeparvovec. Evrysdi led to a sustained >2-fold increase in median SMN protein levels versus baseline in all patients who received prior treatment, irrespective of which treatment was previously received or SMA type.
The overall AE profile of Evrysdi treatment in pre-treated patients was consistent with that of treatment-naïve patients in FIREFISH and SUNFISH. The most common adverse events in all patients were upper respiratory tract infection (17%), pyrexia (17%), headache (16%), nausea (12%), diarrhea (11%), nasopharyngitis (10%) and vomiting (8%). The most common serious adverse events were pneumonia (2%), lower respiratory tract infection (2%), upper respiratory tract infection (2%) and respiratory failure (2%). There were no treatment-related adverse events leading to withdrawal or treatment discontinuation in JEWELFISH, with some patients receiving treatment for more than 3 years. The study is ongoing and the primary analysis will be conducted at month 24.
“Data from the JEWELFISH study, which included a diverse patient population with a high degree of motor impairment, show that Evrysdi has a favorable safety profile in patients previously treated with an SMA-targeting therapy,” said Dr. Claudia Chiriboga, Professor of Neurology and Pediatrics, Department of Neurology, Columbia University Medical Center, New York. “Importantly, the data also suggest a stabilization of motor function in trial participants. As a progressive disease, untreated patients with SMA typically show a decline in motor function over time.”
Roche also presented preliminary efficacy data from RAINBOWFISH, which showed that of the 5 babies treated with Evrysdi for at least 12 months, all achieved sitting without support, rolling and crawling. Of the 5, 2 had 2 SMN copies and 3 had >2 copies. Four of the infants were able to stand unaided and walk independently. In addition, 4 babies reached a maximum score of 64 on the CHOP-INTEND** scale, and 1 scored 63. Data on the primary endpoint, the number of infants sitting without support for at least 5 seconds, will be reported when all primary analysis patients have reached one year of treatment. Recruitment for RAINBOWFISH is ongoing.
The most common adverse events were nasal congestion (33%), cough (25%), teething (25%), vomiting (25%), eczema (17%), abdominal pain (17%), diarrhea (17%), gastroenteritis (17%), papule (rash; 17%) and pyrexia (fever; 17%). There were no adverse events leading to withdrawal or study discontinuation.
Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.
*Hammersmith Functional Motor Scale Expanded
**Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders
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 survival motor neuron (SMN) protein. 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. Evrysdi has been approved in 44 countries and submitted in a further 32 countries.
Evrysdi is currently being evaluated in four 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 adults and children 2 months of age and older.
It is not known if Evrysdi is safe and effective in children under 2 months of age.
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, patients should ask their healthcare provider or pharmacist.
Patients may report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at 1-888-835-2555.
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 and 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.
Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism spectrum disorder. 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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