FDA Grants Priority Review to Biogen’s Drug for Form of ALS

The U.S. Food and Drug Administration granted Biogen’s experimental therapy tofersen priority review for a genetic form of the rare neurodegenerative disease amyotrophic lateral sclerosis.

The agency is expected to act on its approval to market the drug by January 25, 2023. Biogen is pursuing the approval even though the drug failed to meet its primary endpoint of change from baseline to week 28 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) in a phase 3 study. However,  it previously said that trends favoring tofersen were seen across multiple secondary and exploratory measures of biologic activity and clinical function.

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. People with ALS experience muscle weakness and atrophy, causing them to lose independence as they steadily lose the ability to move, speak, eat, and eventually breathe. Average life expectancy for people with ALS is three to five years from time of symptom onset.

Tofersen is an antisense drug being evaluated for the potential treatment of SOD1-ALS. Tofersen binds to SOD1 mRNA, allowing for its degradation by RNase-H to reduce synthesis of SOD1 protein production. In addition to the ongoing open label extension of VALOR, tofersen is being studied in the phase 3 ATLAS study designed to evaluate whether tofersen can delay clinical onset when initiated in pre-symptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity. Biogen licensed tofersen from Ionis Pharmaceuticals, Inc. under a collaborative development and license agreement.

Biogen is seeking approval of tofersen under the FDA’s accelerated approval pathway, based on the use of neurofilament as a surrogate biomarker that is likely to predict clinical benefit. Neurofilaments 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.

Tofersen study results suggest reductions in neurofilament preceded and predicted slowing of decline in measures of clinical and respiratory function, strength, and quality of life. Biogen is committed to ongoing data generation and finalizing the confirmatory data package with the FDA.

The 12-month data from the phase 3 VALOR study and the open label extension study found the most common adverse events in participants receiving tofersen were headache, procedural pain, fall, back pain, and pain in extremities. Most AEs in both VALOR and the OLE were mild to moderate in severity. Serious neurologic events including myelitis, radiculitis, aseptic meningitis, and papilledema, were reported in 6.7 percent of participants receiving tofersen in VALOR and its extension study.

During the FDA review period Biogen said it will maintain its early access program for tofersen, now with participants in more than a dozen countries. Biogen is actively engaging with other regulators around the world and will provide updates when appropriate.

“The available data show that tofersen has the potential to make a meaningful difference for people with SOD1-ALS,” said Priya Singhal, head of global safety and regulatory sciences and interim head of R&D at Biogen. “Pursuing the FDA’s accelerated approval pathway offers the potential to make tofersen available to people living with this fatal, neurodegenerative disease as quickly as possible. If approved, tofersen will be the first treatment to target a genetic cause of ALS and we hope this will pave the way for further advances in this relentless disease.”

Author: Rare Daily Staff