Attempting to push forward an ALS drug despite a failed Phase III study, Biogen saw its FDA review date delayed Monday.
The big biotech announced that the agency pushed back its decision deadline by three months to April 25, 2023 for tofersen, an antisense drug designed to treat a genetic subset of ALS. Biogen had previously received priority review for the application, which will fall under the accelerated approval pathway.
In a press release, Biogen said the FDA had requested additional information, but it’s not clear what they sought. A Biogen spokesperson told Endpoints News, “We aren’t able to provide further detail on our regulatory interactions, but information requests are a standard part of the FDA review process.”
Biogen is trying to get tofersen approved for ALS patients with SOD1 genetic mutations, a population that makes up roughly 2% of the global patient population. Though there are many genes known to be implicated in ALS, SOD1 is the most common. Current research estimates that all genetic mutations account for about 10% of ALS cases worldwide.
SOD1 falls under this umbrella, known as “familial ALS” due to its association with patients’ family histories. The vast majority of other ALS cases, called “sporadic ALS,” make up the other 90%, researchers believe.
There have only been three ALS drugs approved by the FDA, all of which provide only modest effects, and none are specifically targeted toward familial cases. Tofersen attempts to slow SOD1-ALS progression by binding to SOD1 mRNA and reducing “synthesis of SOD1 protein production,” the biotech says.
Using a functional rating scale measuring patient symptoms as the primary goal, tofersen failed a Phase III test late last year. But Biogen is attempting to win accelerated approval based on the drug’s effect on neurofilament light chain, an unproven surrogate biomarker that some researchers believe can measure neuronal cell death.
In patients with neurodegenerative diseases, neurofilament levels can be elevated in blood and cerebrospinal fluid. Biogen theorizes that because tofersen’s data showed a lowering of neurofilament during its clinical trials, the drug works, despite missing the Phase III goals.
The FDA, however, has never approved a drug based on its purported neurofilament-lowering effect. Research showing neurofilament is implicated in ALS is not conclusive, though clinicians note its promise. Other biopharma companies are likely watching this case closely as well, to see if they can center their own new drug applications around neurofilament.
Tofersen stands in contrast to Relyvrio, the recently approved ALS drug from Amylyx Pharmaceuticals, a Boston-area biotech. Whereas tofersen failed its Phase III while showing an effect on neurofilament, Relyvrio earned a modest Phase II success — but showed no correlation to neurofilament levels.
That nuance has allowed Biogen to seek accelerated approval while Amylyx was left searching for, and winning, a full green light. The ball is now in the FDA’s court, and if the path to approval is anything like Amylyx’s, an adcomm (or two) could be in Biogen’s future.
