FDA grants accelerated approval for Biogen ALS drug that treats rare form of the disease

The Food and Drug Administration on Tuesday granted accelerated approval for Biogen's drug tofersen, which treats a rare and aggressive form of the disease known as ALS.

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

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

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

"The findings are reasonably likely to predict a clinical benefit 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 benefit in ALS patients. 

Biogen CEO Chris Viehbacher said in a statement the FDA's decision is a "pivotal moment in ALS research."

"We gained, for the first time, consensus that neurofilament can be used as a surrogate marker reasonably likely to predict clinical benefit in SOD1-ALS," Viehbacher said. "We believe this important scientific advancement will further accelerate innovative drug development for ALS."

ALS, commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease that causes nerve cells in the brain and spinal cord to break down over time. 

Tofersen specifically targets a form of ALS in people with mutations in a specific gene, which are passed down through generations within families.

Those mutations can cause a protein called SOD1 to accumulate to toxic levels, which damages the nervous system and leads to the development 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 form of ALS.

But Fradette noted that SOD1 "does not tell us anything about the impact on disease progression." 

Neurofilament is more strongly associated with the disease's progression and a patient's survival overall, she said. 

"Neurofilament is a tool to see how much neurodegeneration is occurring 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 an average 12% increase in NfL levels in people who were given a placebo. 

Tofersen's failure to slow disease progression in the trial may be due to limitations in the way the study was designed, according to Fradette. She said the trial's length was 28 weeks, which may not have been enough time to observe 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 benefit from being on the drug for a longer period of time. 

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

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

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

In the United States, a little more than 300 people are affected by the SOD1 mutation. 

The SOD1 mutation is associated with 20% of cases that occur within families.

The drug's approval could herald a new area of promising research on how to target the genetic cause of ALS. The disease afflicts an estimated 5,000 new people in the U.S. every year.

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