FDA grants accelerated approval for Biogen ALS drug

The Food and Drug Administration on Tuesday granted accelerated approval for Biogen‘s drug tofersen, which treats a rare and aggressive type of the disease often called ALS.

Accelerated approval is an FDA designation that clears drugs faster in the event that they fill an unmet medical need for serious conditions. The approval requires Biogen and its co-developer Ionis to further study tofersen and confirm its clinical advantages.

If a subsequent trial confirms those advantages, the FDA can grant traditional approval for the drug.

The FDA said its decision relies on mixed late-stage trial results published in 2021, which indicated that tofersen significantly reduced a key protein called neurofilament light. That protein is related to the severity of the mind-wasting disease. 

“The findings are reasonably more likely to predict a clinical profit in patients,” the agency said in a press release.

An independent panel of advisors to the FDA last month similarly voted that tofersen’s effect on neurofilament could produce a clinical profit in ALS patients. 

Biogen CEO Chris Viehbacher said in a press release the FDA’s decision is a “pivotal moment in ALS research.”

“We gained, for the primary time, consensus that neurofilament could be used as a surrogate marker reasonably more likely to predict clinical profit in SOD1-ALS,” Viehbacher said. “We imagine this necessary scientific advancement will further speed up progressive drug development for ALS.”

ALS, commonly often called Lou Gehrig’s disease, is a progressive and fatal neuromuscular disease that causes nerve cells within the brain and spinal cord to interrupt down over time. 

Tofersen specifically targets a type of ALS in individuals with mutations in a selected gene, that are passed down through generations inside families.

Those mutations may cause a protein called SOD1 to build up to toxic levels, which damages the nervous system and results in the event of ALS.

The phase three trial found that patients who received tofersen saw their SOD1 protein levels decline between 26% and 38% compared with those given a placebo. 

Stephanie Fradette, Biogen’s head of ALS development, said those SOD1 protein levels are “indirect evidence” that tofersen targets the rare type of ALS.

But Fradette noted that SOD1 “doesn’t tell us anything concerning the impact on disease progression.” 

Neurofilament is more strongly related to the disease’s progression and a patient’s survival overall, she said. 

“Neurofilament is a tool to see how much neurodegeneration is happening even before someone shows clinical signs and symptoms of ALS,” she told CNBC. “It’s directly correlated with survival.” 

The trial found that patients who received tofersen saw a 55% reduction in NfL levels by week 28 of the study. But there was a median 12% increase in NfL levels in individuals who got a placebo. 

Tofersen’s failure to slow disease progression within the trial could also be as a consequence of limitations in the best way the study was designed, in line with Fradette. She said the trial’s length was 28 weeks, which can not have been enough time to watch the drug’s effect on stalling progression.

Dr. Timothy Miller, a researcher who worked on the late-stage trial, said ongoing studies of tofersen already suggest that patients profit from being on the drug for an extended time period. 

An extension study on patients from the phase three trial found that those that took tofersen experienced improvements in muscle strength and respiratory function after 52 weeks, in line with Miller. 

That extension trial is slated to complete in 2024, he said. 

Just a few thousand people worldwide have been diagnosed with the rare SOD1 mutation, or around 2% of the 168,000 individuals who have ALS all over the world, Biogen said.

In the US, just a little greater than 300 people are affected by the SOD1 mutation. 

The SOD1 mutation is related to 20% of cases that occur inside families.

The drug’s approval could herald a recent area of promising research on the best way to goal the genetic explanation for ALS. The disease afflicts an estimated 5,000 recent people within the U.S. every yr.

Researchers from the National Institutes of Health estimate that ALS cases worldwide will increase by nearly 70% to around 376,000 by 2040.