The Food and Drug Administration has conditionally approved a new ALS medicine in a decision likely to influence how other experimental treatments for the nerve-destroying disease are tested and reviewed.
The medicine, known until now as tofersen, is only for ALS patients who have a specific genetic mutation. Estimates cited by the FDA hold that this group accounts for less than 500 of the roughly 30,000 people in the U.S with the disease.
Until Tuesday, the few therapies that had secured FDA approval did so because they were shown to help patients live a bit better or a bit longer. Tofersen, which will be sold as Qalsody, is different. It failed the key clinical trial meant to demonstrate it can slow the functional decline associated with ALS, or amyotrophic lateral sclerosis.
Rather, tofersen’s approval hinged on its ability to lower levels of “neurofilament light chain,” a protein that’s drawn increasing interest from ALS researchers. It’s the first ALS drug approved based on so-called “biomarker” data, setting a precedent that could provide another, perhaps faster path to market for some developers.
“We believe this important scientific advancement will further accelerate innovative drug development for ALS,” Biogen said in a statement.
Created through a partnership between Biogen and Ionis Pharmaceuticals, tofersen is what’s known as an antisense therapy. If cells are like machines, then antisense drugs act as wrenches in the gears, halting the assembly of unwanted proteins. Tofersen specifically blocks the production of SOD1, a protein that, when mutated, is believed to give rise to ALS.
That key study supporting tofersen’s approval indicated the drug works as designed, with patients who received it experiencing significantly greater reductions in SOD1 compared to those who were given placebos. Treated patients also had substantial declines in neurofilament light chain. Research suggests this protein, when found at elevated levels in the fluid around the brain and spinal cord, is a sign of nerve damage. It is especially prominent in patients with ALS.
Still, tofersen did not meet the study’s main goal. After learning this in 2021, Biogen met with FDA staff multiple times to discuss next steps for its drug. The FDA says it encouraged the company to keep developing tofersen, but also cautioned that securing a full approval based on a single, failed trial would be challenging.
By the spring of 2022, Biogen had decided to use its neurofilament data to pursue “accelerated approval,” a type of marketing clearance given to drugs that the FDA believes are reasonably likely to benefit patients because of their effects on markers of disease. The agency agreed to review Biogen’s application, and initially said it would come to a verdict by Jan. 25, 2023, before extending its review by three months.
The tofersen saga put the FDA in a difficult position. The data backing the drug were mixed. But the agency had also acknowledged the dire need for new ALS drugs as, even with current interventions, most patients live just two to five years after being diagnosed.
Patient advocacy groups have also criticized the FDA, claiming it wasn’t working hard or fast enough to make more potential ALS treatments available to patients. They’ve pointed out how the agency granted accelerated approval to medicines with mixed track records that target other nervous system diseases, such as Biogen’s Aduhelm for Alzheimer’s disease.
Against this backdrop, the FDA in late March convened a committee of outside advisers to weigh tofersen’s pros and cons. While some committee members were hesitant to declare outright that tofersen is an effective treatment for ALS, they all agreed the drug’s effect on neurofilament light chain was “reasonably likely” to predict a clinical benefit.
To analysts, that conclusion raised tofersen’s chances of accelerated approval. Because while the FDA’s actions don’t always reflect the opinions of its advisers, they typically do.
Paul Matteis, an analyst at the investment bank Stifel, wrote in a note to clients after the meeting that the committee’s vote was also a “symbolically important test of the FDA's flexibility” toward new biomarkers for diseases of the central nervous system.
Some ALS drugmakers agree. Kasper Roet, CEO of QurAlis, a Cambridge, Massachusetts-based biotechnology company focused on neurodegenerative disorders, recently told BioPharma Dive it would be “really a very positive development if we can use a biomarker like neurofilament to approve an ALS therapy.”
“In the past that has really shown to be a catalyst of bringing meaningful therapies forward,” he added. “It worked in [multiple sclerosis]. It looks like we might have that now in Alzheimer’s disease. And we think neurofilament can be that for ALS.”
Biogen said it will price its drug “within a range comparable to other recently launched ALS treatments.” Relyvrio, which was broadly approved for ALS last year, costs about $158,000 per year, while an oral version of an older branded medicine called Radicava costs about $170,000 annually.
“We believe this strikes the right balance between the scientific and clinical innovation Qalsody delivers with the need to get this treatment to patients as quickly as possible,” Biogen said in an emailed statement.
Unlike those other two drugs, tofersen is only approved for the small fraction of ALS patients who have mutations in the SOD1 gene. Given that limited population, analysts don’t expect tofersen to become a major product for Biogen. Matteis and the team at Stifel predict the drug will generate around $150 million in annual sales at its peak.
Biogen said it expects out-of-pocket expenses for the “majority” of eligible patients will be less than $50 per month.
Editor’s note: This story has been updated with additional comment from Biogen on Qalsody’s price.