Tofersen Slowed Decline SOD1-Associated Amyotrophic Lateral Sclerosis

In the phase 3 VALOR study (NCT02623699), participants with superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS) had slowed disease progression when treated with tofersen (Biogen, Cambridge, MA).

In the VALOR study, treatment with tofersen vs placebo did not result in statistically significant functional improvement. However, analysis of the VALOR study and the open-label extension of that study suggests tofersen may slow disease progression. 

Data from the VALOR study and OLE demonstrated sustained reductions in SOD1 protein after adjustments for neurofilament levels were made. Participants who received tofersen earlier showed a slowed decline in clinical function, respiratory function, strength, and quality of life.

“I see 3 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,” said Timothy Miller, MD, PhD, principal investigator of VALOR and ALS Center codirector at Washington University School of Medicine, St. Louis. “We are grateful to the dedication from participants, their families, and the sites for taking part in this important study.”

The VALOR study was a 6-month phase 3 randomized double-blind placebo-controlled to evaluate the effects of individuals with SOD1 ALS tofersen 100 mg. Participants (n=108) were randomly assigned to treatment with tofersen (n=72)  or placebo n=36). Of the total participants, 95 enrolled in the ongoing OLE. 

“The ALS community has been actively pursuing new medicines for decades. To have data like these published in NEJM gives us energy and hope. We are now seeing in the data what we suspected about tofersen for a long time – that it has the potential to make a clinical difference for people living with SOD1-ALS,” said Merit Cudkowicz, MD, coprincipal investigator of the VALOR trial and cofounder of the Northeast ALS Consortium, director of the Healey & AMG Center for ALS and chair of Neurology at Massachusetts General Hospital and the Julieanne Dorn professor of Neurology at Harvard Medical School. “The lowering of neurofilament, a marker of axonal injury and neurodegeneration along with the clinical data, highlights the potential of tofersen.”

The most common adverse events (AEs) in participants receiving tofersen in VALOR and the OLE study were procedural pain, headache, pain in the arms or legs, falls, and back pain. Adverse events were reported to be mild to moderate, serious neurologic events included myelitis, chemical or aseptic meningitis, radiculitis, increased intracranial pressure and papilledema.