RARE Daily

CHMP Recommends Marketing Authorization Under Exceptional Circumstances for ALS Drug

February 23, 2024

Rare Daily Staff

The Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion recommending a 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.

If authorized by the European Commission, Qalsody will be the first treatment approved in the European Union to target a genetic cause of ALS, also known as motor neuron disease (MND).

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. Mutations in the SOD1 gene are responsible for approximately 2 percent of the estimated 168,000 people who have ALS globally, and 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.

“The CHMP’s positive opinion reinforces the impact Qalsody can have in SOD1-ALS,” said Priya Singhal, Mhead of Development at Biogen.

The CHMP’s recommendation for Qalsody is based on evidence including the targeted mechanism of action, biomarker, and clinical data. In the 28-week phase 3 VALOR study, reductions of 60 percent in plasma neurofilament light chain (NfL) were observed in participants who received Qalsody compared to the placebo group, suggesting reduced neuronal injury.

Trends towards improvement in the physical abilities of participants who received Qalsody were seen compared to those who received placebo, as measured by the ALS Functional Ratings Scale-Revised. The most common side effects that occurred in ≥10 percent of Qalsody treated participants and more than the placebo arm were pain, fatigue, fever, joint pain, muscle pain and increased levels of white blood cells and proteins in the cerebrospinal fluid. Serious neurologic events, including myelitis and/or radiculitis; papilledema and elevated intracranial pressure; and aseptic meningitis have also been reported.

“The CHMP’s recommendation in support of Qalsody approval provides new hope for the ALS community in Europe,” said Philip Van Damme, professor of neurology and director of the Neuromuscular Reference Center at the University Hospital Leuven in Belgium. “This is a significant milestone for the entire ALS community—for the first time we have a treatment that led to sustained reductions in neurofilament, a marker of axonal injury and neurodegeneration. The Qalsody development program has provided critical learnings on clinical trial design and the use of biomarkers that is advancing the entire field.”

A marketing authorization under exceptional circumstances is recommended when the benefit/risk assessment 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 CHMP’s recommendation for Qalsody will now be reviewed by the European Commission for a decision on a marketing authorization in the European Union, with a decision expected in the second quarter of 2024.

Qalsody is an antisense oligonucleotide designed to bind to SOD1 mRNA to reduce SOD1 protein production. The U.S. Food and Drug Administration granted accelerated approval for Qalsody to treat ALS in adults who have a mutation in the SOD1 gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with Qalsody. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

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

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