RARE Daily

European Commission Approval Biogen’s Qalsody to Treat a Rare, Genetic Form of ALS

May 31, 2024

Rare Daily Staff

The European Commission granted marketing authorization under exceptional circumstances for Biogen’s Qalsody for the treatment of adults with amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene.

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 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. Mutations in the SOD1 gene are responsible for approximately 2 percent of the estimated 168,000 people who have ALS globally (SOD1-ALS). 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 (tofersen) is an antisense oligonucleotide (ASO) designed to bind to SOD1 mRNA to reduce SOD1 protein production and is the first treatment approved in the European Union to target a genetic cause of ALS, also known as motor neuron disease.

The marketing authorization for Qalsody is granted under exceptional circumstances, which is recommended when the benefit/risk assessment of a treatment is determined to be positive but due to the rarity of the disease, it is unlikely that comprehensive data can be obtained under normal conditions of use. The European Medicines Agency (EMA) recommended QALSODY’s designation as an orphan medicinal product be maintained.

“The European Commission’s approval of Qalsody is a testament to the unwavering dedication of the ALS community – people living with ALS and their loved ones, scientists, clinicians, and advocates – who have worked together over the past two decades to bring forward this important new treatment for the SOD1-ALS community,” said Stephanie Fradette, head of the Neuromuscular Development Unit at Biogen. “We are working with the medical community and local authorities to bring Qalsody to people living with SOD1-ALS across the region as quickly as possible.”

The approval of Qalsody is based on the totality of evidence, including the targeted mechanism of action, biomarker, and clinical data.

In the randomized, double-blind, placebo-controlled phase 3 VALOR study, patients were randomized 2:1 to receive treatment with either Qalsody 100 mg or placebo for 24 weeks. The primary efficacy endpoint was the change from baseline to Week 28 in the ALS Functional Ratings Scale-Revised total score.

The results numerically favored tofersen, but were not statistically significant. At Week 28, mean plasma neurofilament light chain (NfL), a marker of axonal injury and neurodegeneration, was reduced by 55 percent in the tofersen-treated participants, compared to a 12 percent increase with placebo.

Very common adverse reactions (may affect more than 1 in 10 people) reported in Qalsody -treated participants were pain (back pain, pain in arms or legs), feeling tired, muscle and joint pain, fever, and an increase in protein and/or white blood cell count occurring in the fluid that surrounds the brain and spinal cord.

Biogen licensed Qalsody from Ionis Pharmaceuticals under a collaborative development and license agreement. Qalsody was discovered by Ionis.

Photo: Stephanie Fradette, head of the Neuromuscular Development Unit at Biogen

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