The FDA granted (Qalsody) for amyotrophic lateral sclerosis (ALS) patients with mutations in the SOD1 gene, the agency announced on Tuesday.
The drug was cleared under the accelerated approval pathway, a program that uses a surrogate endpoint to approve drugs for serious conditions with an unmet medical need. For tofersen, the FDA's decision was based on plasma levels of neurofilament light (NfL), a marker of neurodegeneration.
Tofersen is the first ALS drug approved under the accelerated approval pathway and the second ALS drug approved in less than a year. It's also the first approved drug that targets a genetic cause of ALS.
Around 2% of ALS cases are caused by mutations in SOD1. Tofersen is an antisense oligonucleotide that targets SOD1 mRNA to reduce SOD1 protein synthesis.
"Every opportunity to make a new treatment available that can stop or slow down this disease is a win for the whole community," said Larry Falivena, a member of the ALS Association's board of trustees, who has SOD1 ALS and participated in tofersen trials, in a .
"Tofersen could be the opportunity to break the cycle of genetic ALS for families who have been devastated by ALS for generations," Falivena added.
Tofersen's effectiveness was evaluated in the 28-week phase III VALOR clinical trial. The drug did not meet its primary endpoint of improving motor control or muscle strength compared with placebo, but it did reduce SOD1 protein in cerebrospinal fluid (CSF) and lowered plasma NfL. Data from the open-label extension suggested long-term use of tofersen may have clinical benefit.
"We see clear evidence that the drug slows down the initiating factor -- a SOD1 mutation -- as well as the neurodegenerative disease process," said investigator Timothy Miller, MD, PhD, of Washington University in St. Louis, when VALOR trial results were published.
"We didn't see substantial clinical improvement at 6 months, but the stabilization in function and strength at longer time points suggests it may take time for people to heal from the damage that has already been caused," Miller observed.
The most common side effects seen in tofersen trials were pain, fatigue, arthralgia, increased CSF white blood cells, and myalgia, the FDA said. Additional risks are described in the drug's , the agency added.
Tofersen is administered intrathecally at a recommended dosage 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.
To confirm clinical benefit, the drug is being studied in the phase III , which is assessing whether tofersen can delay clinical onset of ALS in presymptomatic patients with a SOD1 genetic mutation and biomarker evidence of disease activity. ATLAS is scheduled to be completed in 2027.