Health Canada Accepts for Review New Drug Submission for Tofersen for Treatment of Rare, Genetic Form of ALS

Tofersen is an antisense oligonucleotide (ASO) designed to bind to SOD1 mRNA to reduce SOD1 protein production. The U.S. Food and Drug Administration granted accelerated approval for QALSODY™ (tofersen) to treat amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with tofersen. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).³ Tofersen also received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommending its marketing authorization under exceptional circumstances for the treatment of adults with ALS associated with a mutation in the SOD1 gene.⁴ A decision on a marketing authorization in the European Union is expected in the second quarter of 2024.

Biogen licensed tofersen from Ionis Pharmaceuticals, Inc. under a collaborative development and license agreement. Tofersen was discovered by Ionis.

In addition to an ongoing open label extension (OLE) of VALOR, tofersen is being studied in the Phase 3, randomized, placebo-controlled ATLAS study to evaluate whether tofersen can delay clinical onset when initiated in presymptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity (elevated plasma NfL). More details about ATLAS (NCT04856982) can be found at clinicaltrials.gov.

Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and the spinal cord that are responsible for controlling voluntary muscle movement. People with ALS experience muscle weakness and atrophy, causing them to lose independence as they steadily lose the ability to move, speak, eat, and eventually breathe. Average life expectancy for people with ALS is three to five years from time of symptom onset.⁵

Multiple genes have been implicated in ALS. Genetic testing helps determine if a person’s ALS is associated with a genetic mutation, even in individuals without a known family history of the disease. More than 15 percent of people with ALS are thought to have a genetic form of the disease;⁶ however, they may not have a known family history of the disease.¹

SOD1-ALS is diagnosed in approximately two percent of all ALS cases.¹ In people with SOD1-ALS, mutations in their SOD1 gene cause their bodies to create a toxic misfolded form of SOD1 protein. This toxic protein causes motor neurons to degenerate, resulting in progressive muscle weakness, loss of function, and eventually, death.⁶

For over a decade, Biogen has been committed to advancing ALS research to provide a deeper understanding of all forms of the disease. The company has continued to invest in and pioneer research despite making the difficult decision to discontinue a late-stage ALS asset in 2013. Biogen has applied important learnings to its portfolio of assets for genetic and other forms of ALS, with the goal of increasing the probability of bringing a potential therapy to patients in need. These applied learnings include evaluating genetically validated targets in defined patient populations, pursuing the most appropriate modality for each target and employing sensitive clinical endpoints. In addition to tofersen, the company has a pipeline of investigational drugs being evaluated in ALS, including BIIB105.

Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patient lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment, to deliver long-term growth.

Biogen has been proudly serving Canadian patients for more than 25 years. For information about Biogen Canada, please visit www.biogen.ca. 

1. Brown CA, Lally C, Kupelian V, Flanders WD. Estimated Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1 and C9orf72 Genetic Variants. Neuroepidemiology. 2021;55(5):342-353. doi: 10.1159/000516752. Epub 2021 Jul 9.
2. ALS Society of Canada, About ALS. https://als.ca/what-is-als/about-als/ Accessed: February 2024.
3. QALSODY Prescribing Information, Cambridge, MA: Biogen. https://www.biogencdn.com/us/pdfs/qalsody-prescribing-information.pdf Accessed: February 2024.
4. European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP), Summary of Opinion. https://www.ema.europa.eu/en/medicines/human/EPAR/qalsody   Accessed: February 2024.
5. National Institute of Neurological Disorders and Stroke. Amyotrophic Lateral Sclerosis (ALS). Available at: https://www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als.  Accessed: February 2024.
6. Akcimen F, Lopez ER, Landers JE, et al. Amyotrophic lateral sclerosis: translating genetic discoveries into therapies. Nat Rev Genet. 2023. https://doi.org/10.1038/s41576-023-00592-y