FDA to Hold Advisory Committee Meeting for ALS Drug

FDA plans to hold an advisory committee meeting to review data submitted as part of the new drug application for tofersen, an investigational product to treat patients with superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS). The Peripheral and Central Nervous System Drugs Advisory Committee meeting is scheduled for March 22, 2023.

Developed by Ionis Pharmaceuticals and licensed to Biogen, tofersen is an antisense drug that binds to SODI mRNA. SOD1 was the first gene in which mutations were found to cause the neurodegenerative disease. SOD1-ALS is an ultra-rare form of ALS that affects about 330 people in the United States. It is progressive, leads to the loss of everyday functions and is fatal.

Biogen’s NDA for tofersen was accepted for priority review by the FDA under the accelerated approval pathway and has a Prescription Drug User Fee Act action date of April 25, 2023.

Biogen is seeking approval based on the use of a neurofilament as a surrogate biomarker. Neurofilaments are normal proteins found in healthy neurons; they 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.

Related: FDA Extends Review Time for Biogen’s ALS Therapy

The application is based the phase 3 VALOR trial and an open-label extension study, as well as integrated 12-month results from both of these studies. The six-month VALOR study did not meet the primary endpoint of change from baseline to week 28 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. But trends of reduced disease progression across multiple secondary and exploratory endpoints were observed. The 12-month integrated data showed that earlier initiation of tofersen led to sustained reductions in neurofilament and slowed decline across multiple efficacy endpoints.

Timothy Miller, M.D., Ph.D.

The results of VALOR and its open-label extension study were published in September 2022 in the New England Journal of Medicine. Investigators wrote that tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma but did not improve clinical endpoints and was associated with adverse events.

“I see three key take home points from these data. First, tofersen clearly leads to lowering of SOD1 protein, as would be expected. Second there is substantial lowering of neurofilament levels, which I interpret as potentially slowing the underlying disease process. And third, there is a meaningful clinical benefit when looking at the later time points in the open label extension,” Timothy Miller, M.D., Ph.D., principal investigator of VALOR and ALS Center co-director at Washington University School of Medicine, St. Louis, said in a press release when the publication of the study was announced