Biogen has announced that its antisense drug tofersen has failed to meet its primary endpoint in the phase 3 VALOR trial involving people with superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS).
ALS is a progressive, fatal neurodegenerative disease with an average survival of 3-5 years and SOD1-ALS is a rare, genetic form that accounts for 2% of the estimated 168,000 people who have the disease globally.
However, all is not lost for those with the disease, as Biogen reports “signs of reduced disease progression” across multiple secondary and exploratory measures of biologic activity and clinical function, including motor function, respiratory function and quality of life.
While announcing tofersen’s top-line results, Biogen is emphasising “the totality of evidence” and its ongoing open-label extension, which “showed that participants who started tofersen earlier experienced better outcomes, further suggesting a positive clinical effect”.
Patient organisation, the MND Association, met the news with “disappointment tinged with some encouragement”, welcoming the “potentially encouraging indications” that will need to be investigated further.
“There are questions that need to be addressed, on whether the drug needs to be given earlier in the disease and over a longer time period, as well as whether the levels of the toxic SOD1 protein are still too high and need to be knocked down even more,” said its director of research development, Dr Brian Dickie.
VALOR principal investigator Dr Timothy Miller from the ALS Center at Washington University School of Medicine, St Louis, said: “The wait for new options has been long and difficult for the ALS community, and we welcome this important research advancement in this difficult to treat disease space.”
Following these results, Biogen will now expand its early access programme for tofersen, which means all eligible SOD1-ALS patients worldwide will receive the drug free of charge.
Tofersen, which acts by binding to the superoxide dismutase 1 (SOD1) mRNA thereby reducing the protein’s synthesis, is also being evaluated to see whether it can delay clinical onset in pre-symptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity in the phase 3 ATLAS study.
This is the second late-stage failure announced by Biogen in recent months after its gene therapy cotoretigene toliparvovec (BIIB112) did not meet its primary endpoint in patients with X-linked retinitis pigmentosa, a rare, inherited retinal disease that is associated with progressive vision loss, in May.