FDA approves Qalsody for SOD-1 ALS

Key takeaways:

• Tofersen, which targets SOD1 mRNA, is administered intrathecally in three initial doses, followed by a maintenance dose every 28 days.
• The approval was based on a reduction in plasma neurofilament light.

The FDA has approved Qalsody, an antisense oligonucleotide, to treat individuals with ALS associated with a mutation in the superoxide dismutase 1 gene.

According to an FDA press release, Qalsody (tofersen, Biogen) targets superoxide dismutase 1 (SOD1) mRNA to reduce the synthesis of SOD1 protein. The accelerated approval was based on a reduction in plasma neurofilament light (NfL), a blood-based biomarker that indicates nerve injury and neurodegeneration.

Tofersen is administered intrathecally, the FDA stated, with a recommended dose of 100 mg (15 mL) per administration. Patients receive three initial doses administered at 14-day intervals, followed by a maintenance dose every 28 days.

The therapeutic was evaluated in a 28-week, randomized, double-blind, placebo-controlled clinical study, in which 108 individuals (median age, 49.8 years; 43% women; 64% white) received either 100 mg tofersen (n = 72) or placebo (n = 36) for 24 weeks, in three loading doses followed by five maintenance doses.

According to the release, patients treated with tofersen had significant reductions in plasma NfL concentration at week 28 compared with the placebo group, with the observed reduction in NfL consistent across all subgroups based on sex, disease duration since symptom onset, site of onset and use of other medications for ALS treatment.

In March, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted unanimously that tofersen may be considered for potential accelerated approval, ruling that available evidence was sufficient to conclude that a reduction in plasma NfL chain concentration in tofersen-treated patients was likely to predict clinical benefit for patients with SOD1-ALS.

“For more than a decade, Biogen has been steadfast in our commitment to pursuing treatments for ALS, and 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,” Christopher A. Viehbacher, Biogen president and CEO, said in an email to Healio. “We believe this important scientific advancement will further accelerate innovative drug development for ALS.”

A phase 3 randomized, double-blind, placebo-controlled study is underway to further confirm benefits of tofersen in non-symptomatic carriers of the SOD1 genetic mutation, the release stated.