Health Canada now reviewing Qalsody as treatment for SOD1-ALS
If approved, therapy would be 1st in Canada to target genetic cause of ALS
Health Canada is now reviewing Qalsody (tofersen) as a potential treatment for people with amyotrophic lateral sclerosis (ALS) who carry mutations in the SOD1 gene, according to the therapy’s developer Biogen.
The Canadian regulatory authority agreed to review Biogen’s application for the therapy’s approval, with its decision expected in early 2025, according to a company press release.
If approved, Qalsody will become the first and only therapy approved in Canada to target a genetic cause of ALS. Qalsody already is approved in the U.S. and has been recommended for approval in the European Union to treat ALS-SOD1 patients.
The application “represents a critical milestone for the Canadian ALS community and those suffering from this ultra-rare genetic form of the disease that robs them of time with loved ones,”said Eric Tse, vice president and general manager of Biogen Canada.
“For over a decade, Biogen has been committed to advancing ALS research to provide a deeper understanding of this devastating disease. We are passionate about doing what we can to make a difference and are deeply committed to the rare disease community,” Tse added.
Request for approval based on data from VALOR trial
Mutations in the SOD1 gene are found in as many as 20% of people with familial ALS and in up to 2% of sporadic ALS cases. These mutations lead to the production of an abnormal SOD1 protein, which tends to accumulate and form toxic clumps inside nerve cells, causing damage.
Qalsody belongs to a class of therapies called antisense oligonucleotides, or ASOs. Such therapies prevent the production of disease-causing proteins by interfering with their messenger RNA (mRNA) — an intermediate molecule derived from DNA that’s used as a template for protein production.
The drug is designed to bind to SOD1’s mRNA and target it for degradation, preventing the cell’s protein-making machinery from reading this template to produce the protein. This causes a marked reduction in SOD1 levels, which is expected to slow disease progression and extend survival.
The treatment is administered via intrathecal injection, or an injection into the spinal canal. In the U.S., it’s given as three initial three doses 14 days apart, followed by maintenance doses every 28 days.
Qalsody’s submission to Health Canada was based on data from Part 3 of the VALOR trial (NCT02623699), which enrolled 108 adults with ALS and a confirmed SOD1 mutation. It aimed to assess the safety and efficacy of Qalsody versus a placebo.
Participants were randomly assigned to receive eight intrathecal injections of either 100 mg of Qalsody or a placebo over six months.
The trial’s main goal was to assess changes in functional disability, as measured with the ALS Functional Rating Scale-Revised (ALSFRS-R), in a group of 60 patients with fast-progressing disease after about seven months.
That goal was not met, but there were some indications that Qalsody slowed the decline in measures of lung function and muscle strength. Also, the treatment significantly reduced spinal fluid levels of SOD1 and blood levels of neurofilament light chain (NfL), a marker of nerve cell degeneration, both of which increased in the placebo group.
After completing the trial, 95 participants joined an open-label extension study (NCT03070119), in which all are receiving Qalsody for up to seven years. That study is expected to be concluded in June.
After one year, data from the Phase 3 study and its extension showed that patients who were always on Qalsody experienced a smaller drop in their ALSFRS-R scores relative to those who were initially assigned to the placebo and then switched to the treatment in the extension study. That decline averaged six points for those always treated versus 9.5 points for patients who switched from the placebo.
The early-start group also showed significant extensions in survival and in time to death or permanent ventilation.
A Phase 3 trial called ATLAS (NCT04856982), launched in 2021, is now testing whether Qalsody can delay the onset of disease symptoms in individuals with a SOD1 mutation who already show signs of neuronal damage — specifically, who have elevated blood levels of NfL — but are asymptomatic.
The trial, slated to run through 2027, is expected to involve about 150 patients who receive the treatment or a placebo for up to two years. Top-line data also is anticipated in 2027.
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