The European Commission has approved Qalsody (tofersen) as a treatment for amyotrophic lateral sclerosis (ALS) associated with mutations in the SOD1 gene, known as SOD1-ALS.
Qalsody was specifically granted marketing authorization under exceptional circumstances — a pathway recommended when the benefit-to-risk assessment for a therapy is favorable, but the condition itself is too rare to reasonably allow the type of comprehensive testing needed for a regular approval.
The decision makes Qalsody the first medication to be approved in the European Union to target any genetic cause of ALS, according to the therapy’s maker Biogen.
“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,” Stephanie Fradette, head of the neuromuscular development unit at Biogen, said in a company press release.
Fradette added that Biogen is “working with the medical community and local authorities to bring Qalsody to people living with SOD1-ALS across the region as quickly as possible.”
Advocacy group welcomes approval of Qalsody for SOD1-ALS in Europe
The approval was met with celebration by the European Organisation for Professionals and People living with ALS (EUpALS), an advocacy group.
“At EUpALS, we are excited that people with SOD1-ALS in Europe will have access to Qalsody, the first treatment targeting a genetic cause of ALS. This is a major milestone for the ALS community, showing that ALS is a treatable disease,” said Evy Reviers, chairwoman of the EUpALS.
“As a representative of the European ALS community, I am excited to enter a new evolution in the common fight against ALS,” Reviers added.
The approval of Qalsody in Europe comes about a year after the therapy was conditionally approved in the U.S. Thanks to a Biogen early access program, about 330 people with SOD1-ALS across 18 EU countries have already accessed the therapy, according to the company.
At EUpALS, we are excited that people with SOD1-ALS in Europe will have access to Qalsody, the first treatment targeting a genetic cause of ALS. This is a major milestone for the ALS community, showing that ALS is a treatable disease.
The European Commission’s decision to approve Qalsody was based on the totality of preclinical and clinical data available, including findings from the Phase 1/2/3 VALOR clinical trial (NCT02623699).
The Phase 3 portion of VALOR tested Qalsody against a placebo, given via six injections into the spinal canal over six months, in 108 people with SOD1-ALS. Patients could continue to receive the standard ALS medication riluzole (sold as Rilutek among others) during that period.
The study was designed to show that patients given Qalsody would have less decline in functional measures after six months. While the results numerically favored the medication, they were not significant, and the trial failed to meet its primary goal.
Despite the negative main findings, analyses indicated the therapy lowered levels of the nerve damage biomarker neurofilament light chain (NfL) by 55%, compared with a 12% increase in the placebo arm, according to the company.
Also, long-term data from the trial’s open-label extension (NCT03070119) have indicated that patients who started on Qalsody during the main study had their disease progress more slowly and were less likely to die or experience lung function decline compared with those who started on the therapy six months later.
“Qalsody’s approval represents a paradigm shift in the treatment of SOD1-ALS, offering hope to patients and loved ones who have long awaited a breakthrough,” said Philip Van Damme, MD, PhD, professor of neurology and director of the Neuromuscular Reference Center at the University Hospital Leuven, in Belgium.
Van Damme noted that “the European Academy of Neurology has confirmed new treatment guidelines for ALS that recognize Qalsody should be offered as [a] first-line treatment for patients with SOD1-ALS.”
Phase 3 trial now testing if therapy can delay onset in those with SOD1 mutation
ALS is a disorder marked by the degeneration of motor neurons, the specialized nerve cells that control voluntary movement. While its causes aren’t fully understood, as many as 20% of cases of familial ALS and 2% of sporadic ALS cases are associated with mutations in SOD1.
The SOD1 gene provides instructions to make a protein that’s also called SOD1, short for superoxide dismutase one. ALS-associated mutations result in the production of an abnormal version of this protein that cannot function properly and is prone to forming toxic clumps inside nerve cells.
Qalsody is an RNA-based therapy that works to prevent the toxic SOD1 protein from being made by targeting the SOD1 gene’s messenger RNA (mRNA), an intermediary molecule that’s made when the gene is read to produce a protein.
The therapy is given via intrathecal injection into the spinal canal, every other week for three loading doses, and then monthly thereafter. Common side effects of Qalsody include pain, fatigue, fever, and increased levels of proteins or immune cells in the fluid around the brain.
Biogen is now running a Phase 3 trial dubbed ATLAS (NCT04856982) that’s testing whether Qalsody can delay the onset of ALS in people who carry a SOD1 mutation but don’t yet have any symptoms of the disease.