The US Food and Drug Administration (FDA) has approved Biogen QALSODY (tofersen) 100 mg/15mL injection for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene.
This indication was approved based on accelerated approval based on the reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Further approval for this indication may depend on verification of clinical benefit in confirmatory trials. The ongoing ATLAS phase 3 study of toffersen in people with presymptomatic SOD1-ALS will serve as a confirmatory trial.
Neurofilaments are proteins that are released from neurons when they are damaged, making them a marker of neurodegeneration.
“For more than a decade, Biogen has been steadfast in our commitment to pursuing ALS treatment, and I want to thank the scientists and the entire ALS community who have worked tirelessly to deliver this first treatment of its kind. to people with SOD1-ALS,” said Christopher A. Viehbacher, president and chief executive of Biogen.
“Today also marks an important moment in ALS research as we gain, for the first time, consensus that neurofilaments can be used as surrogate markers that can most likely predict clinical benefit in SOD1-ALS. We believe this important scientific advance will further accelerate the development of innovative drugs for ALS.”
QALSODY Biogen: The first approved treatment
QALSODY is the first treatment approved to target the genetic causes of ALS. Biogen is working with Ionis Pharmaceuticals on the initial development of toffersen.
“Since the SOD1 mutation was first identified as a cause of ALS 30 years ago, the familial ALS community has been searching for genetically targeted treatments. QALSODY offers families who have lost generations in the prime of their lives to this devastating disease, a therapy that targets the underlying causes of SOD1-ALS. Today marks an important moment in ALS research as QALSODY is the first approved ALS treatment based on a biomarker,” said Jean Swidler, chair of Genetic ALS & FTD: End the Legacy.
“We are excited to see what future therapies are developed, now it is understood that lowering the levels of neurofilaments provides important evidence that treatment influences neurodegenerative processes.”
QALSODY trial results
The efficacy of QALSODY was assessed in a 28-week randomized, double-blind, placebo-controlled clinical study in patients aged 23 to 78 years, with weakness caused by ALS and central laboratory-confirmed SOD1 mutation.
Over 28 weeks on VALOR, participants in the primary analysis population treated with QALSODY experienced less decline from baseline as measured by the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) compared with placebo, although the results were not statistically significant. In the overall treated population, QALSODY-treated participants experienced a 55% decrease in plasma NfL compared with a 12% increase in placebo-treated participants.
In addition, CSF SOD1 protein levels, an indirect measure of target engagement, were reduced by 35% in the QALSODY-treated group compared with 2% in the matched placebo group.
QALSODY approval is supported by 12 months integration results from VALOR and its OLE comparing earlier initiation of tofferent (in early VALOR) with delayed initiation of tofferent (six months later, in OLE), published in The New British Journal of Medicine.
“I have observed a positive effect of QALSODY in slowing the progression of ALS in people with the SOD1 mutation,” said Timothy M. Miller, principal investigator of the QALSODY clinical trial and co-director of the ALS Center at the University of Washington School of Medicine in Louis.
“The FDA’s approval of QALSODY gives me hope that people living with this rare form of ALS may experience reduced strength, clinical function, and respiratory function.”
QALSODY will be available for delivery in the US to healthcare providers in about a week. Biogen anticipates there may be variations in the timing of treatment as institutions and treatment centers learn about QALSODY.
About Biogen WRONG
QALSODY (tofersen) is a prescription medication used to treat amyotrophic lateral sclerosis in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication was approved based on accelerated approval based on the reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY.
It is an antisense oligonucleotide (ASO) designed to bind to SOD1 mRNA to reduce SOD1 protein production.
Toffersen is licensed by Biogen from Ionis Pharmaceuticals, Inc. under a collaborative development and licensing agreement. Toffersen was discovered by Ionis.
About amyotrophic lateral sclerosis and SOD1-ALS
Amyotrophic lateral sclerosis is a rare, progressive, and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and spinal cord that are responsible for controlling voluntary muscle movements. People with ALS experience muscle weakness and atrophy, causing them to lose independence as they continue to lose the ability to move, speak, eat, and eventually breathe. The average life expectancy for people with ALS is three to five years from the onset of symptoms.
Several genes have been implicated in ALS. Genetic testing helps determine whether a person’s ALS is associated with a genetic mutation, even in individuals with no known family history of the disease. SOD1-ALS is diagnosed in about 2% of all ALS cases, with about 330 people in the US living with the disease. More than 15% 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.
Other companies are also making headway in the fight against ALS. Last year, the FDA approved Cellenkos’ ALS drug for trials. Japanese researchers identified a genetic variant that causes ALS in some patients, and BrainEver and 3P Biopharmaceuticals also announced in 2022 that they are developing a drug with hopes of curing ALS.