Genentech, a member of the Roche Group, today announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) and granted Priority Review for risdiplam, an investigational survival motor neuron-2 (SMN-2) splicing modifier for spinal muscular atrophy (SMA). Risdiplam is designed to increase and sustain SMN protein levels both throughout the central nervous system and peripheral tissues of the body. The FDA is expected to make a decision on approval by May 24, 2020.
“The FIREFISH and SUNFISH trials were designed to represent the real world spectrum of people living with SMA and include many people previously underrepresented in clinical trials,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We look forward to working closely with the FDA to explore broad access to risdiplam for all individuals in the community who might benefit.”
The risdiplam NDA submission incorporates 12-month data from the dose-finding Part 1 sections of the FIREFISH and SUNFISH pivotal studies, as well as data from the confirmatory Part 2 of SUNFISH. FIREFISH is an open-label, two-part seamless pivotal clinical trial in infants with Type 1 SMA. Part 1 was a dose-escalation study in 21 infants aged 1-7 months. The primary objective of Part 1, which evaluated efficacy as an exploratory endpoint, was to assess the safety profile of risdiplam in infants and determine the dose for Part 2, which is a pivotal, single-arm trial evaluating risdiplam in 41 infants with Type 1 SMA for 24 months, followed by an open-label extension.
SUNFISH is a two-part, double-blind, placebo-controlled pivotal clinical trial in children and young adults (2-25 years old) with Type 2 or 3 SMA. Part 1 determined the dose for the confirmatory Part 2 and evaluated efficacy as an exploratory endpoint. SUNFISH Part 2 is a large placebo-controlled trial evaluating treatment for people with Type 2 or 3 SMA. SUNFISH Part 2 recently met its primary endpoint of change from baseline in the Motor Function Measure 32 (MFM-32) scale.* No treatment-related safety findings leading to study withdrawal have been seen in any risdiplam trial to date. Safety for risdiplam was consistent with its known safety profile and no new safety signals were identified. Results will be presented at an upcoming medical congress.
If approved, risdiplam, an orally administered liquid, would be the first at-home administered medicine for people living with SMA. In addition to the studies included in the NDA submission, risdiplam is being studied in a broad clinical trial program in SMA, with patients ranging from newborns to 60 years old, and includes patients previously treated with SMA therapies.
Genentech leads the clinical development of risdiplam as part of a collaboration with the SMA Foundation and PTC Therapeutics, and would commercialize the medicine in the United States if approved.
Priority Review designation is granted to medicines that the FDA considers to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. Previously, the FDA also granted Orphan Drug Designation for risdiplam in January 2017, followed by Fast Track Designation in April 2017.
*MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA.
Spinal muscular atrophy (SMA) is a severe, inherited, progressive neuromuscular disease that causes devastating muscle atrophy and disease-related complications. It is the most common genetic cause of infant mortality and one of the most common rare diseases, affecting approximately one in 11,000 babies. SMA leads to the progressive loss of nerve cells in the spinal cord that control muscle movement. 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.
SMA is caused by a mutation in the survival motor neuron-1 (SMN-1) gene that results in a deficiency of SMN protein. SMN protein is found throughout the body and increasing evidence suggests SMA is a multi-system disorder and the loss of SMN protein may affect many tissues and cells, which can stop the body from functioning.
Risdiplam is an investigational, orally administered liquid survival motor neuron-2 (SMN-2) splicing modifier for SMA. It is designed to increase and sustain SMN protein levels both throughout the central nervous system and peripheral tissues of the body. It is being evaluated for its potential ability to help the SMN-2 gene produce more functional SMN protein throughout the body.
Risdiplam is currently being evaluated in four multicenter trials in people with SMA.
• FIREFISH (NCT02913482) an ongoing open-label, two-part pivotal clinical trial in infants with Type 1 SMA.
• SUNFISH (NCT02908685) a two-part, double-blind, placebo-controlled pivotal clinical trial in children and young adults (2-25 years old) with Type 2 or 3 SMA.
• JEWELFISH (NCT03032172) an open-label exploratory trial in people with SMA Type 1, 2 or 3, aged 6 months to 60 years who have been previously treated with SMA therapy, gene therapy or olesoxime. The study is currently recruiting.
• RAINBOWFISH (NCT03779334) an open-label, single-arm, multicenter study, investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of risdiplam in babies (~n=25), from birth to 6 weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is currently recruiting.
About Genentech in neuroscience
Neuroscience is a major focus of research and development at Genentech and Roche. The company’s goal is to develop treatment options based on the biology of the nervous system to help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche have more than a dozen investigational medicines in clinical development for diseases that include multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and autism.
Founded more than 40 years ago, Genentech (gene.com) 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.