Qalsody approved in Canada for ALS tied to SOD1 mutations
Therapy given conditional approval, awaiting further evidence of benefit
Health Canada has conditionally approved Qalsody (tofersen) for the treatment of adults with amyotrophic lateral sclerosis (ALS) associated with mutations in the SOD1 gene.
Qalsody, designed to lower levels of the toxic protein that drives the disease for these patients, is the first treatment to directly target the root cause of SOD1-ALS, according to its developer, Biogen.
“We’re thrilled to bring forward Qalsody as a treatment for individuals living with SOD1-ALS, a rare form of this devastating disease,” Eric Tse, general manager of Biogen Canada, said in a company press release, noting that the approval “marks a milestone in ALS research.”
Qalsody conditionally approved in US, use in exceptional cases in EU
Qalsody has a similar conditional approval in the U.S., and it is also approved under exceptional circumstances in the European Union.
Conditional approval means that a therapy can be marketed based on preliminary clinical trial evidence of likely benefit for patients. Confirmatory data will be needed for the treatment to advance to full approval.
In the case of Qalsody, these conditional approvals were based largely on trial data showing that the treatment can lower levels of neurofilament light chain (NfL), an established biomarker of nerve damage, with preliminary evidence suggesting the therapy may slow disease progression.
Tammy Moore, CEO of the ALS Society of Canada, said the Canadian approval is “a pivotal moment for the ALS community and brings renewed hope to people living with SOD1-ALS. It highlights the ongoing progress in research, offering a new and promising approach to improving what it means to live with this life-altering diagnosis.”
In ALS, the nerve cells involved in voluntary muscle control, called motor neurons, are progressively lost. For some people, the disease is caused by mutations in SOD1 that result in production of a faulty SOD1 protein that toxically clumps up in motor neurons and damages them.
Qalsody, given via monthly injections directly into the spinal canal, is designed to bind to and promote the degradation of the genetic template molecule needed to produce SOD1 from the gene that encodes it. This is expected to lower levels of the toxic protein, slowing disease progression in this patient group.
“Qalsody is the first therapy to directly target the root cause of SOD1-ALS, addressing the misfolded proteins responsible for the disease — a distinction that sets it apart from other ALS treatments, which primarily focus on symptom management rather than modifying the disease itself,” said Angela Genge, MD, director of the ALS Centre of Excellence for Research and Patient Care at McGill University in Montreal, and an investigator in clinical trials of the therapy.
VALOR trial indicated early treatment helped to slow ALS progression
The therapy’s approval in Canada, as elsewhere, was based largely on data from the Phase 3 part of the VALOR clinical trial (NCT02623699) and its open-label extension study (NCT03070119).
Although initial VALOR data failed to demonstrate a slowing in ALS progression among treated adults relative to those on a placebo, findings spanning the entire trial and its extension study indicated that an earlier start to treatment slowed disease progression and lowered a person’s risk of death. Qalsody’s use also was associated with slower declines in lung function and muscle strength.
Qalsody was linked to reductions in NfL levels, and patients who exhibited early drops in this blood biomarker were found to have slower disease progression.
Additional analyses of VALOR and extension study data, as well as results from the ongoing ATLAS Phase 3 trial (NCT04856982), may provide confirmatory data to support the treatment’s conversion to full approval.
ATLAS, expected to enroll 150 patients at sites worldwide, is testing Qalsody against a placebo in presymptomatic adults, those with no manifest ALS symptoms. Eligible patients all carry SOD1 mutations associated with rapidly progressing disease and have elevated NfL levels in the blood.
The trial’s main goal is to evaluate the proportion of patients who develop ALS symptoms over the first two years of treatment. ATLAS is expected to finish in 2027.
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