Tofersen

Tofersen
Clinical data
Trade namesQalsody
AHFS/Drugs.comMonograph
MedlinePlusa623024
License data
Routes of
administration		Intrathecal
ATC code
Legal status
Legal status
Identifiers
  • all-P-ambo-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-adenylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'→5')-2'-O-(2-methoxyethyl)-guanylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-P-thioadenylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thioadenylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-P-thioadenylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-adenylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methylcytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyluridine
CAS Number
PubChem CID
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC230H317N72O123P19S15
Molar mass7127.85 g·mol−1
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  • Key:AZBXTZOFHIRMCD-SIVATHJTSA-N

Tofersen, sold under the brand name Qalsody, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS). Tofersen is an antisense oligonucleotide that targets the production of superoxide dismutase 1, an enzyme whose mutant form is commonly associated with ALS. It is administered as an intrathecal injection.

Tofersen is approved for medical use in the US and EU, as well as other nations such as Australia, Bahrain, Canada, Chile, China, Japan, Oman, Qatar, Spain and the UAE. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.

Common side effects include fatigue, arthralgia, increased cerebrospinal (brain and spinal cord) fluid, pleocytosis and myalgia. Tofersen can also cause more serious side effects, such as inflammation of the spinal cord (myelitis) and the nerve roots, swelling of the optic nerve (papilledema), elevated cranial pressure and inflammation of the brain linings.

Uses

Tofersen is indicated to treat ALS patients associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS). Tofersen is not approved for use in children under 18 years; there are no determined effective dosages, safety or researched side effects.

Tofersen can be used for patients at various stages of ALS progression. However, early implementation of Tofersen is beneficial as it slows down motor decline and muscle strength, and motor neuron damage is less extensive.

Prescription

Tofersen is prescribed only to treat ALS caused by the SOD1 mutation. Tofersen has a single, standardized dosage amount for all patients: 100 mg/ 15 mL per administration.

Administration

Tofersen is administered intrathecally via a lumbar puncture. This is because Tofersen cannot cross the blood-brain barrier, and intrathecal administration allows Tofersen to circulate with the CSF and reach the CNS (spinal cord and brain tissues), where it can act on motor neurons.

Tofersen is administered by a healthcare professional in a medical clinic. Prior to administration of each dose, a lumbar puncture needle removes 10 mL of CSF. This prevents fluid volume overload and the risk of increased pressure.

The first 3 dosages are called the loading doses: they are given every 14 days. The fourth dosage and onwards are called maintenance doses: they are administered at 28-day intervals. Each dose is slowly injected over 1-3 minutes.

Adverse effects

The most common side effects include fatigue, arthralgia, headaches, back pain, myalgia, an increase in CSF and pleocytosis (increase of white blood cells in CSF).

Tofersen can cause more serious side effects, such as inflammation of the spinal cord (myelitis) and the nerve roots, swelling of the optic nerve (papilledema), elevated cranial pressure and inflammation of the brain linings (meningitis). These require immediate clinical attention and care.

However, the majority of patients who experienced these serious side effects resolved the symptoms without discontinuing Tofersen. Specifically, inflammation resolved in 4 of the 6 affected patients, while all patients experiencing papilledema and increased cranial pressure (4 patients) and meningitis (1 patient), recovered without stopping Tofersen.

Causes of adverse effects

Tofersen is an antisense oligonucleotide (ASO), which have been known to trigger immune and pro-inflammatory responses in the CNS. This can lead to pleocytosis.

Side effects from Tofersen can also arise due to the direct effects of the drug, sensitivity with lumbar puncture administration and introduction of foreign materials into the CNS.

History

Tofersen was developed by Ionis Pharmaceuticals and was licensed to and co-developed by Biogen.

In February 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Qalsody, intended for the treatment of a type of amyotrophic lateral sclerosis caused by a defective superoxide dismutase 1 (SOD1) protein. The applicant for this medicinal product is Biogen Netherlands B.V. Tofersen was approved for medical use in the European Union in May 2024.

The FDA approved tofersen for priority review, orphan drug, and fast track designations.

Clinical trials

Tofersen's effectiveness was evaluated in a 28-week, randomized, double-blind, placebo-controlled clinical study with 147 participants with weakness attributable to ALS and a lab-confirmed SOD-1 mutation. The study randomly assigned 108 participants in a 2:1 ratio to receive treatment with either tofersen 100 mg (n = 72) or placebo (n = 36) for 24 weeks (3 loading doses followed by 5 maintenance doses). Approximately 43% were female; 57% male; 64% White; and 8% Asian. The average age was 49.8 years (23-78).

The stage III clinical trial was conducted by the Neuroscience Institute and Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield.

Society and culture

Economics

Around 1-2% of US ALS cases carry the specific SOD1 mutation targeted by the drug. Fewer than 500 patients a year are expected to be eligible for the drug, which is expected to cost over $100,000 for a year's treatment.

References

  1. ↑ "Register of Innovative Drugs". Health Canada. 3 November 2006. Retrieved 17 April 2025.
  2. ↑ "Qalsody- tofersen injection". DailyMed. 25 April 2023. Archived from the original on 8 May 2023. Retrieved 10 June 2023.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene" (Press release). U.S. Food and Drug Administration (FDA). 25 April 2023. Archived from the original on 25 April 2023. Retrieved 25 April 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  4. 1 2 3 4 "Qalsody EPAR". European Medicines Agency (EMA). 22 February 2024. Retrieved 24 February 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. 1 2 "Qalsody PI". Union Register of medicinal products. 3 June 2024. Retrieved 7 September 2024.
  6. ↑ "FDA Grants Accelerated Approval for Qalsody (tofersen) for SOD1-ALS, a Major Scientific Advancement as the First Treatment to Target a Genetic Cause of ALS" (Press release). Biogen. 25 April 2023. Archived from the original on 25 April 2023. Retrieved 25 April 2023 – via GlobeNewswire.
  7. 1 2 3 "Tofersen/Qalsody". www.als-mnd.org. Retrieved 2 November 2026.
  8. 1 2 New Drug Therapy Approvals 2023. U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original (PDF) on 10 January 2024. Retrieved 9 January 2024.
  9. 1 2 3 4 5 6 7 8 "QALSODY® (tofersen)| Official Patient site". www.qalsody.com. Biogen. 1 January 2024. Archived from the original on 8 October 2026. Retrieved 2 November 2026.
  10. ↑ "Tofersen (intrathecal route) - Side effects & uses". Mayo Clinic. Archived from the original on 1 October 2026. Retrieved 2 November 2026.
  11. ↑ George J (23 December 2025). "Long-Term Tofersen Use May Slow ALS Progression, 3-Year Data Suggest". MedPage Today.
  12. ↑ "Tofersen Dosage". Drugs.com.
  13. 1 2 3 4 5 6 7 8 9 "Qalsody". Qalsody (tofersen). Biogen. 1 August 2024.
  14. 1 2 3 "Tofersen Injection: MedlinePlus Drug Information". medlineplus.gov. Retrieved 2 November 2026.
  15. 1 2 3 4 5 6 7 Cerillo JL (12 November 2023). "Tofersen". NCBI, NLM, NIH. National Institute of Health.
  16. 1 2 3 4 Lovett A, Chary S, Babu S, Bruneteau G, Glass JD, Karlsborg M, et al. (June 2025). "Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis". Muscle & Nerve. 71 (6): 1006–1015. doi:10.1002/mus.28372. PMC 12060635. PMID 40017137.
  17. ↑ Liu A (1 May 2019). "Biogen's antisense ALS drug shows promise in early clinical trial". FierceBiotech. Archived from the original on 2 February 2023. Retrieved 25 April 2023.
  18. ↑ Langreth R (22 March 2023). "Biogen's ALS Drug Gets Partial Backing From FDA Panel". Bloomberg News. Retrieved 25 April 2023.
  19. ↑ "New treatment for rare motor neuron disease recommended for approval". European Medicines Agency (EMA) (Press release). 23 February 2024. Retrieved 24 February 2024.
  20. ↑ "FDA approves drug which helps to slow progression of rare form of MND". The University of Sheffield. 28 April 2023. Retrieved 16 May 2024.
  21. ↑ Berdyński M, Miszta P, Safranow K, Andersen PM, Morita M, Filipek S, et al. (January 2022). "SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity". Scientific Reports. 12 (1) 103. Bibcode:2022NatSR..12..103B. doi:10.1038/s41598-021-03891-8. PMC 8742055. PMID 34996976.
  22. ↑ Constantino A (25 April 2023). "FDA grants accelerated approval for Biogen ALS drug that treats rare form of the disease". CNBC. Archived from the original on 25 April 2023. Retrieved 25 April 2023.
  23. ↑ Constantino A (22 March 2023). "FDA advisors vote against effectiveness of Biogen's ALS drug for rare and aggressive form of the disease". CNBC. Archived from the original on 10 April 2023. Retrieved 25 April 2023.
  24. ↑ Robins R (25 April 2023). "F.D.A. Approves Drug for Rare Form of A.L.S." The New York Times. Archived from the original on 25 April 2023. Retrieved 25 April 2023.