Chemistry:Tofersen

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

The most common side effects include fatigue, arthralgia (joint pain), increased cerebrospinal (brain and spinal cord) fluid white blood cells, and myalgia (muscle pain).[1]

Tofersen was approved for medical use in the United States in April 2023,[1][2] and in the European Union in May 2024.[3] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[4]

Medical uses

Tofersen is indicated to treat people with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS).[1]

History

Tofersen was developed by Ionis Pharmaceuticals and was licensed to, and co-developed by, Biogen.[5][6]

The effectiveness of tofersen was evaluated in a 28-week, randomized, double-blind, placebo-controlled clinical study in 147 participants with weakness attributable to amyotrophic lateral sclerosis and a superoxide dismutase 1 (SOD-1) mutation confirmed by a central laboratory.[1] 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 (three loading doses followed by five maintenance doses).[1] The participants were approximately 43% female; 57% male; 64% White; and 8% Asian.[1] The average age was 49.8 years (range from 23 to 78 years).[1]

The stage III clinical trial was conducted by the Neuroscience Institute and Sheffield Institute for Translational Neuroscience (SITraN), both at the University of Sheffield.[7]

The US Food and Drug Administration (FDA) granted the application for tofersen priority review, orphan drug, and fast track designations.[1][4]

Society and culture

Economics

Only around 1-2% of ALS cases diagnosed in the United States each year carry the specific SOD1 mutation targeted by the drug.[8] 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.[1][9][10][11]

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.[3][12] The applicant for this medicinal product is Biogen Netherlands B.V.[3] Tofersen was approved for medical use in the European Union in May 2024.[13]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Cite error: Invalid <ref> tag; no text was provided for refs named FDA Qalsody
  2. ↑ "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.
  3. ↑ 3.0 3.1 3.2 "Qalsody EPAR". 22 February 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/qalsody.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. ↑ 4.0 4.1 (PDF) New Drug Therapy Approvals 2023 (Report). January 2024. https://www.fda.gov/media/175253/download. Retrieved 9 January 2024. 
  5. ↑ Liu, Angus (1 May 2019). "Biogen's antisense ALS drug shows promise in early clinical trial". FierceBiotech. https://www.fiercebiotech.com/research/biogen-s-antisense-als-drug-shows-promise-early-clinical-study. 
  6. ↑ Langreth, Robert (22 March 2023). "Biogen's ALS Drug Gets Partial Backing From FDA Panel". Bloomberg News. https://www.bloomberg.com/news/articles/2023-03-22/biogen-s-als-drug-tofersen-gets-partial-backing-from-fda-panel. 
  7. ↑ "FDA approves drug which helps to slow progression of rare form of MND" (in en). 28 April 2023. https://www.sheffield.ac.uk/news/fda-approves-drug-which-helps-slow-progression-rare-form-mnd. 
  8. ↑ "SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity". Scientific Reports 12 (1). January 2022. doi:10.1038/s41598-021-03891-8. PMID 34996976. Bibcode: 2022NatSR..12..103B. 
  9. ↑ Constantino, Annika (25 April 2023). "FDA grants accelerated approval for Biogen ALS drug that treats rare form of the disease". CNBC. https://www.cnbc.com/2023/04/25/fda-grants-accelerated-approval-biogen-als-drug.html. 
  10. ↑ Constantino, Annika (22 March 2023). "FDA advisors vote against effectiveness of Biogen's ALS drug for rare and aggressive form of the disease". CNBC. https://www.cnbc.com/2023/03/22/fda-advisors-vote-against-effectiveness-of-biogen-als-drug.html. 
  11. ↑ Robins, Rebecca (25 April 2023). "F.D.A. Approves Drug for Rare Form of A.L.S.". The New York Times. https://www.nytimes.com/2023/04/25/business/biogen-fda-als-drug.html. 
  12. ↑ "New treatment for rare motor neuron disease recommended for approval". European Medicines Agency (EMA) (Press release). 23 February 2024. Retrieved 24 February 2024.
  13. ↑ "Qalsody PI". 3 June 2024. https://ec.europa.eu/health/documents/community-register/html/h1783.htm. 



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