Health Canada is now reviewing Qalsody (tofersen) as a potential treatment for people with amyotrophic lateral sclerosis (ALS) who carry mutations in SOD1 gene, according to the therapy’s developer, Biogen.
The Canadian regulator has agreed to review Biogen’s application for approval of the therapy, with a decision expected in early 2025, according to a company press release.
If approved, Qalsody would become the first and only therapy approved in Canada targeting a genetic cause of ALS. Qalsody is already approved in the US and has been recommended for approval in the European Union for the treatment of patients with ALS-SOD1.
The application “represents a critical milestone for the Canadian ALS community and those suffering from this ultra-rare genetic form of the disease, which robs them of time with loved ones,” said Eric Tse, vice president and general manager of Biogen Canada.
“For more than 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 the VALOR trial
Mutations in SOD1 are found in up to 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 that tends to accumulate and form toxic clumps in 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 is used as a template for protein production.
The drug is designed to bind to SOD1 mRNA and target it for degradation, preventing the cell’s protein-making machinery from reading this template to produce the protein. This leads to a significant reduction in SOD1 levels, which is expected to slow disease progression and prolong survival.
Treatment is administered by intrathecal injection or spinal canal injection. In the US, it is given as three initial doses 14 days apart, followed by maintenance doses every 28 days.
Health Canada’s submission of Qalsody is based on data from part 3 of the VALOR trial (NCT02623699), which enrolled 108 adults with ALS and confirmed SOD1 mutation. It aimed to assess the safety and efficacy of Qalsody versus placebo.
Participants were randomly assigned to receive eight intrathecal injections of 100 mg Qalsody or placebo over six months.
The primary aim of the study was to assess changes in functional impairment, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), in a group of 60 patients with rapidly progressive disease after approximately seven months.
This goal was not met, but there was some indication that Qalsody slowed the decline in measures of lung function and muscle strength. Also, the treatment significantly reduced CSF SOD1 levels and blood levels of neurofilament light chain (NfL), a marker of nerve cell degeneration, both of which were increased in the placebo group.
After the trial was completed, 95 participants joined an open-label extension study (NCT03070119) in which all received Qalsody for up to seven years. This study is expected to be completed in June.
After one year, data from the phase 3 study and its follow-up study showed that patients who were always on Qalsody had a smaller decline in their ALSFRS-R scores than those who were initially assigned to placebo and after these crossed over to treatment in the follow-up study. This drop averaged six points for those always treated versus 9.5 points for patients who switched from placebo.
The early start group also showed a significant prolongation of survival and time to death or permanent ventilation.
A phase 3 trial called ATLAS (NCT04856982), starting in 2021, is now testing whether Qalsody can delay the onset of disease symptoms in individuals with SOD1 mutation, who already show signs of neuronal damage – in particular, who have elevated blood levels of NfL – but are asymptomatic.
The study, scheduled to run until 2027, is expected to include about 150 patients who receive treatment or a placebo for up to two years. The first data are also expected in 2027.