The Food and Drug Administration (FDA) has granted accelerated approval to Biogen’s new drug, Tofersen, for treating a rare and aggressive form of amyotrophic lateral sclerosis (ALS). The approval was granted as Tofersen has filled an unmet medical need for serious conditions. However, Biogen and its co-developer Ionis must further study Tofersen and verify its clinical benefits, and if the benefits are confirmed, the FDA can grant traditional approval for the drug.
Details of the Approval
The FDA’s decision to approve Tofersen is based on mixed late-stage trial results published in 2021, which indicate that Tofersen significantly reduced the key protein in ALS known as neurofilament light. The protein is associated with the severity of the disease, and the findings are reasonably likely to predict a clinical benefit in patients. An independent panel of advisors to the FDA similarly voted that Tofersen’s effect on neurofilament could produce a clinical benefit in ALS patients.
The drug has been designed to target a form of ALS found in people with mutations in a specific gene that is passed down through generations within families, causing a protein called SOD1 to accumulate to toxic levels that damage the nervous system and lead 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.
Possible Limitations
Although Tofersen’s failure to slow disease progression in the phase three trial may be due to limitations in the way the study was designed, ongoing studies of Tofersen already suggest that patients benefit from being on the drug for a longer period. 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.
The approval of Tofersen could herald a new area of promising research on how to target the genetic cause of ALS, which afflicts an estimated 5,000 new people in the U.S. every year. As a few thousand people worldwide have been diagnosed with the rare SOD1 mutation, and the SOD1 mutation is associated with 20% of cases that occur within families, the drug’s approval is expected to have a significant impact on ALS research. Researchers from the National Institutes of Health estimate that ALS cases worldwide will increase by nearly 70% to around 376,000 by 2040.
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