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FDA Approves Biogen Antisense Oligo Drug Targeting Genetic Form of ALS

3D rendered image of interconnected neurons with electrical pulses

NEW YORK – The first treatment targeting a genetic form of amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig's disease, has been approved by the US Food and Drug Administration, the agency said Tuesday.

The FDA granted accelerated approval to Qalsody (tofersen), which Biogen licensed from Ionis Pharmaceuticals as part of a collaborative development agreement, as a treatment for patients with a rare form of ALS that is associated with a mutation in the SOD1 gene (SOD1-ALS). Qalsody, an antisense oligonucleotide delivered through a spinal injection, binds to and helps degrade SOD1 mRNA to reduce the production of SOD1 protein.

The FDA said it granted approval based on findings from a Phase III study that demonstrated Qalsody leads to a reduction in plasma neurofilament light (NfL), a blood-based biomarker associated with axonal injury and neurodegeneration.

"Patients receiving Qalsody had nominally significant reductions in plasma NfL concentration at week 28 compared to the placebo arm," the FDA wrote in a statement. "The findings are reasonably likely to predict a clinical benefit in patients."

The same Phase III study, however, failed to meet a primary endpoint of improving patients' physical functions, leading some neurologists to question whether there was enough evidence to approve the drug. Biogen, in its application to the FDA, also included data from an open-label extension study, in which investigators found that being on Qalsody longer led to slower declines in clinical function for patients, although those findings were not statistically significant.

Results from an ongoing Phase III study will be used to confirm clinical benefits of Qalsody, according to the FDA.   "I want to thank the scientists as well as the entire ALS community who have all worked tirelessly to bring this first-of-its-kind treatment to people with SOD1-ALS," Biogen President and CEO Christopher Viehbacher said in a statement. "Today also marks a pivotal moment in ALS research as 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.”

Biogen said it plans to make Qalsody available to US healthcare providers in about one week.

Roughly 2 percent of ALS cases are related to mutations in the SOD1 gene. In total, variants in more than 40 genes have been associated with ALS, though SOD1 is the most common.