Qalsody (tofersen) has been approved in the United States and the European Union as a treatment targeting a genetic cause of ALS

Qalsody (tofersen) is a prescription medicine used to treat amyotrophic lateral sclerosis (ALS) in adults who have a pathogenic variant (also known as a mutation) in the superoxide dismutase 1 (SOD1) gene. The therapy is an antisense oligonucleotide that targets SOD1 mRNA to reduce the synthesis of SOD1 protein. 

The treatment is administered intrathecally, a route of administration of drugs via injection into the spinal fluid, via lumbar puncture, with a recommended dosage of 100 mg/15 mL per administration. Individuals receive three initial doses administered at 14-day intervals, followed by a maintenance dose every 28 days. Intrathecal injection is a routine procedure. 

The SOD1 gene provides instructions for making a protein that helps protect our body’s cells from damage caused by harmful chemicals called reactive oxygen species. Mutations in this gene can cause a type of ALS that damages the nerve cells responsible for controlling movement, called motor neurons. In these cases, the abnormal protein made by the genetic variant is toxic to the motor neurons, leading to their death and resulting in the symptoms of ALS. 

Approximately two per cent of people living with ALS have a pathogenic variant in the SOD1 gene, the second most common known cause of genetic ALS. Most individuals with a SOD1 pathogenic variant have a known family history of ALS. Some people without any obvious familial connection to ALS have tested positive for SOD1 pathogenic variants. 

Individuals must have a pathogenic variant in the SOD1 gene to benefit from the treatment.  

If you’re interested in learning more about the treatment, please get in touch with an ALS clinician, who will be able to interpret the clinical information about the drug as it pertains to individual situations. 

In most situations, people with pathogenic variants in SOD1 will be aware of a family history of ALS, where multiple relatives have been diagnosed in the past. If you have a family history of ALS and are interested to know if it might be related to SOD1, please connect with an ALS clinician or research@als.ca for support in next steps.  

In some cases, SOD1 pathogenic variants have been found in people living with ALS who do not have an obvious family history. Much of the ALS field is evolving to genetic testing practices for all people with ALS, but this is not common practice everywhere. If you have ALS and are interested in finding out if you have a SOD1 pathogenic variant, please speak to your clinician or contact research@als.ca for support. 

An ongoing clinical trial with Qalsody (tofersen) is also searching for individuals with specific SOD1 pathogenic variants to be monitored for participation in a placebo-controlled clinical trial where treatment can begin when the disease process has started but before any clinical symptoms have been identified. A biomarker called neurofilament light (NfL) has been established to detect the early stages of this underlying process and Qalsody (tofersen) will be tested to study if it can delay the onset of symptoms. Individuals randomized to placebo will be provided active Qalsody (tofersen) treatment upon diagnosis, which is still earlier than anyone has ever been treated in previous clinical trials. If you have a known SOD1 related family history but do not have ALS, and are interested in learning more, please contact an ALS clinician or research@als.ca for support. 

If you have a known family history of ALS, do not know if it is linked to SOD1, and are interested in learning more, please contact research@als.ca for support.  

ALS Canada aims to provide opportunities for more learning and information about SOD1-ALS in the days ahead, in conjunction with the Canadian ALS Research Network (CALS). It is important that we do everything possible to make sure anyone who stands to benefit from Qalsody (tofersen) is identified and able to access the treatment. 

Canada has been involved in the clinical trials of Qalsody (tofersen) since the initial Phase 1 study. Participants from that study, as well as the completed Phase 3 (VALOR) clinical trial, are still accessing Qalsody (tofersen) through an ongoing open-label extension study. At this time, this open-label extension study is only available to individuals who participated in the clinical trial. 

There is an ongoing clinical trial of Qalsody (tofersen) for presymptomatic SOD1 carriers, recruiting at sites in Canada. This clinical trial is specifically for individuals who have specific SOD1 mutations but have not yet developed any symptoms of ALS. It requires regular monitoring to detect the initial stages of biological ALS occurring, before the onset of symptoms. More information about the study can be found at:

• https://www.alsatlasstudy.com/
• https://www.tricals.org/en/news/the-atlas-study-a-clinical-trial-for-people-who-want-to-contribute-to-sod1-als-research/. 

For further information, you can contact one of the Canadian trial sites listed here.  

Qalsody (tofersen) is currently available to eligible individuals through Health Canada’s Special Access Program (SAP). On March 19, 2024, Biogen Canada announced that Health Canada has accepted its New Drug Submission (NDS) for tofersen. This step triggers a thorough regulatory review of the therapy, which will result in the decision as to whether tofersen will be approved for use in Canada. 

A regulatory decision on the New Drug Submission is expected in early 2025. 

There are several Canadians who took part in the clinical trials and continue to access the therapy through open label extension (OLE) provided by Biogen. Additionally, Canadians have been able to access the therapy through the Special Access Program (SAP). 

Please speak with an ALS clinician for more information. 

Qalsody (tofersen) is currently available in Canada via Health Canada’s Special Access Program (SAP). Anyone diagnosed with SOD1-ALS should have access to the treatment through speaking to their clinician. You may also seek further information via research@als.ca. 

Biogen has applied to Health Canada for approval on March 19, 2024. A regulatory decision on the New Drug Submission is expected in early 2025. 

Health Canada conducts a review of the drug to assess its safety, efficacy, and quality. The process begins when the drug manufacturer files a New Drug Submission (NDS) with Health Canada. Health Canada must accept the New Drug Submission before the regulatory review begins.  

There are three timelines under which Health Canada conducts drug reviews: 

• Standard Review, which is almost a one-year process (300 days) 
• Notice of Compliance with Conditions, which is an approximately 200-day process 

• Priority Review, which is a six-month process (180 days) 

Based on the review, Health Canada decides to either approve or reject the drug. If approved, the drug is granted a Notice of Compliance (NOC), which allows it to be sold in Canada and can be prescribed by physicians.  

We believe any new innovative ALS therapy should be granted priority review status. Due to the swift progression and terminal nature of the disease, people living with ALS cannot afford to wait almost a year for Health Canada to review a therapy. During this time, people will experience further loss of function, and ultimately, approximately 1,000 Canadians will die of ALS. Visit this blog post on How new drugs become approved and accessible to Canadians for more information. 

Qalsody (tofersen) is not yet approved by Health Canada. Individuals with SOD1-ALS who wish to access Qalsody (tofersen) should not need to obtain it in the United States or Europe and should ask an ALS clinician about the Health Canada Special Access Program.