There is currently no treatment for SOD1-ALS. If approved, tofersen, which Biogen licensed from Ionis Pharmaceuticals, Inc. under a collaborative development and license agreement, would be the first treatment to target a genetic cause of ALS.
Tofersen is designed to bind to SOD1 mRNA, allowing for its degradation by RNase-H in an effort to reduce synthesis of SOD1 protein production.
The application for a New Drug Application (NDA) has been granted priority review and given a Prescription Drug User Fee Act (PDUFA) action date of January 25, 2023, and the US Food and Drug Administration (FDA) has also indicated it will hold an advisory committee meeting for Biogen’s application, on a yet-to-be determined date.
The Cambridge, Massachusetts headquartered company is seeking approval of tofersen under the FDA’s accelerated approval pathway, based on the use of neurofilament as a surrogate biomarker that is reasonably likely to predict clinical benefit.
The US regulator's accelerated approval pathway has come in for criticism after Biogen's controversial alzheimer's drug, Aducanumab, was approved that way.
Neurofilaments, said Biogen, are normal proteins found in healthy neurons, that are increased in blood and cerebrospinal fluid when damage has been done to neurons or their axons and are a marker of neurodegeneration. In ALS, higher levels of neurofilaments have been found to predict more rapid decline in clinical function and shortened survival.
The company outlined how the NDA is supported by results from the tofersen clinical development program, including the VALOR Phase 3 study and latest 12-month integrated results from VALOR and its open label extension study recently presented at the European Network to Cure ALS (ENCALS) meeting.
“The 12-month results showed that individuals with SOD1-ALS who started tofersen earlier experienced a slower rate of decline in clinical and respiratory function, strength and quality of life. These are critical measures for people living with this devastating disease,” said Timothy Miller, principal investigator of VALOR and ALS Center co-director at Washington University School of Medicine, St Louis.
Biogen is maintaining its early access program for tofersen, now with participants in over a dozen countries, during the FDA review period.
Amyotrophic lateral sclerosis (ALS) is a rare, progressive and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and the spinal cord that are responsible for controlling voluntary muscle movement. Multiple genes have been implicated in the disease.