Biogen and Ionis are dropping an experimental treatment for amyotrophic lateral sclerosis, or ALS, a neurodegenerative disease in which people lose muscle control over time.
The decision was based on biomarker results from a Phase 1/2 study called ALSpire, which enrolled 99 adults with ALS. The treatment, labeled BIIB105, also did not improve measures of function, breathing and strength, Biogen and Ionis said Thursday in a press release.
BIIB105 is an antisense oligonucleotide designed by Ionis to cut expression of a protein called ataxin-2, which is found most abundantly in the central nervous system and believed to be implicated in a number of neurodegenerative disorders.
The treatment significantly lowered levels of ataxin-2 measured in the cerebrospinal fluid of those with ALS in the early-stage trial. However, it didn’t reduce levels of neurofilament light chain, a biomarker that Biogen and Ionis used to win approval last year for Qalsody, their treatment for a rare form of ALS.
Viehbacher on neurofilament, Qalsody and risk-taking
Despite the failed trial, Biogen CEO Chris Viehbacher said that the biotech’s ability to take more risks than large pharma companies allows it to make decisions more quickly and redirect resources to other areas.
Chris ViehbacherThe comments were made Thursday at the Financial Times’ US Pharma and Biotech Summit held in partnership with Endpoints News. (Endpoints News is a part of FT Specialist, a unit of the Financial Times.) They illustrate Viehbacher’s thinking about how Biogen’s identity is evolving after he took over as CEO in November 2022. Larger pharma companies, he said, focus much of their attention on making sure earnings reports are predictable, whereas Biogen can and should be taking more risks.
Viehbacher cited Qalsody as an example, noting Biogen “will never make a return on that investment.”
“But that product makes such a difference to patients. We get news reports daily about people getting out of their wheelchairs and walking,” he said. “And we also validated neurofilament.”
The FDA does not list neurofilament as a validated surrogate endpoint on its website, though it approved Qalsody using the biomarker. Thursday morning, the Foundation for the National Institutes of Health said it had received a letter from the FDA signaling the agency’s intent to qualify neurofilament as a biomarker for frontotemporal degeneration.
Qalsody was approved for about 1% to 2% of ALS patients with a mutation called SOD1. Its approval, which hinged on how the treatment reduced levels of neurofilament, paved the way for using the biomarker as a key measure in clinical trials. Neurofilament is a protein shed by damaged neurons.
Separately, Biogen elected not to license a therapy that Ionis developed for Angelman syndrome, a rare genetic neurodevelopmental condition. Ionis plans to independently take the treatment into pivotal studies following a Phase 1/2 trial readout that suggested the treatment improved measures of motor skills, cognition and communication. Ultragenyx is also preparing for a pivotal study in Angelman syndrome, while Roche stopped development on its candidate last year.
Editor’s note: This story was updated to note that FDA does not count neurofilament as a validated surrogate endpoint.