FDA Grants Accelerated Approval for Biogen’s Qalsody Certain ALS Patients

Rare Daily Staff

The U.S. Food and Drug Administration granted Biogen accelerated approval for Qalsody for the treatment of the neurodegenerative condition amyotrophic lateral sclerosis.

The approval is for adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. The agency granted accelerated approval to Biogen based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with Qalsody. Neurofilaments are proteins that are released from neurons when they are damaged, making them a marker of neurodegeneration.

Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials. The ongoing phase 3 ATLAS study of Qalsody in people with pre-symptomatic SOD1-ALS will serve as the confirmatory trial.

“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,” said Christopher Viehbacher, president and CEO of Biogen. “We believe this important scientific advancement will further accelerate innovative drug development for ALS.”

Amyotrophic lateral sclerosis (ALS) is a rare, progressive and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and the spinal cord that are responsible for controlling voluntary muscle movement. People with ALS experience muscle weakness and atrophy, causing them to lose independence as they steadily lose the ability to move, speak, eat, and eventually breathe. Average life expectancy for people with ALS is three to five years from the time of symptom onset.

Multiple genes have been implicated in ALS. Genetic testing helps determine if a person’s ALS is associated with a genetic mutation, even in individuals without a known family history of the disease. SOD1-ALS is diagnosed in approximately 2 percent of all ALS cases, with about 330 people in the United States living with the disease. More than 15 percent of people with ALS are thought to have a genetic form of the disease, however, they may not have a known family history of the disease. In people with SOD1-ALS, mutations in their SOD1 gene cause their bodies to create a toxic misfolded form of SOD1 protein. This toxic protein causes motor neurons to degenerate, resulting in progressive muscle weakness, loss of function, and eventually, death.

Qalsody is the first approved treatment to target a genetic cause of ALS. Biogen collaborated with Ionis Pharmaceuticals on the early development of Qalsody. Qalsody is an antisense oligonucleotide designed to bind to SOD1 mRNA to reduce SOD1 protein production. Qalsody is administered intrathecally as three loading doses administered at 14-day intervals followed by maintenance doses administered once every 28 days thereafter.

The efficacy of Qalsody was assessed in a 28-week randomized, double-blind, placebo-controlled clinical study in patients 23 to 78 years of age with weakness attributable to ALS and a SOD1 mutation confirmed by a central laboratory. A total of 108 patients were randomized 2:1 to receive treatment with either Qalsody 100 mg or placebo for 24 weeks (three loading doses followed by 5 maintenance doses). Concomitant riluzole and/or edaravone use was permitted for patients and at baseline 62 percent of patients were taking riluzone, and 8 percent of patients were taking edaravone.

Patients receiving Qalsody had nominally significant reductions in plasma NfL concentration at Week 28 compared to the placebo arm. The findings are reasonably likely to predict a clinical benefit in patients. The observed reduction in NfL was consistent across all subgroups based on sex, disease duration since symptom onset, site of onset, and use of other medications for ALS treatment.

Qalsody will be made available for shipment in the United States to healthcare providers in approximately one week. Biogen anticipates there may be variation in time to treatment as institutions and treatment centers learn about Qalsody.

Photo: Christopher Viehbacher, president and CEO of Biogen