Tofersen

Medication

Tofersen

Clinical data
Trade names| Qalsody
AHFS/Drugs.com| Monograph
MedlinePlus| a623024
License data|

* US DailyMed: Tofersen

Routes of
administration| Intrathecal
ATC code|

* N07XX22 (WHO)

Legal status
Legal status|

* US: ℞-only[1][2]
* EU: Rx-only[3][4]

Identifiers
CAS Number|

* 2088232-70-4

DrugBank|

* DB14782

UNII|

* 2NU6F9601K

KEGG|

* D11811

Chemical and physical data
Formula| C230H317N72O123P19S15
Molar mass| 7127.85 g·mol−1

Tofersen, sold under the brand name Qalsody, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS).[2] 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.[2]

The most common side effects include fatigue, arthralgia (joint pain), increased cerebrospinal (brain and spinal cord) fluid white blood cells, and myalgia (muscle pain).[2]

Tofersen was approved for medical use in the United States in April 2023,[2][5] 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.[6]

## Medical uses

[edit]

Tofersen is indicated to treat people with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS).[2]

## History

[edit]

Tofersen was developed by Ionis Pharmaceuticals and was licensed to, and co-developed by, Biogen.[7][8]

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.[2] 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).[2] The participants were approximately 43% female; 57% male; 64% White; and 8% Asian.[2] The average age was 49.8 years (range from 23 to 78 years).[2]

The stage III clinical trial was conducted by the Neuroscience Institute and Sheffield Institute for Translational Neuroscience (SITraN), both at the University of Sheffield.[9]

The US Food and Drug Administration (FDA) granted the application for tofersen priority review, orphan drug, and fast track designations.[2][6]

## Society and culture

[edit]

### Economics

[edit]

Only around 1-2% of ALS cases diagnosed in the United States each year carry the specific SOD1 mutation targeted by the drug.[10] 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.[2][11][12][13]

## Legal status

[edit]

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][14] 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.[4]

## References

[edit]

1. ^ "Qalsody- tofersen injection". DailyMed. 25 April 2023. Archived from the original on 8 May 2023. Retrieved 10 June 2023.
2. ^ a b c d e f g h i j k l "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. This article incorporates text from this source, which is in the public domain.
3. ^ a b c d "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.
4. ^ a b "Qalsody PI". Union Register of medicinal products. 3 June 2024. Retrieved 7 September 2024.
5. ^ "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.
6. ^ a b New Drug Therapy Approvals 2023 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 10 January 2024. Retrieved 9 January 2024.
7. ^ 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.
8. ^ Langreth R (22 March 2023). "Biogen's ALS Drug Gets Partial Backing From FDA Panel". Bloomberg News. Retrieved 25 April 2023.
9. ^ "FDA approves drug which helps to slow progression of rare form of MND". www.sheffield.ac.uk. 28 April 2023. Retrieved 16 May 2024.
10. ^ 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.
11. ^ 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.
12. ^ 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.
13. ^ 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.
14. ^ "New treatment for rare motor neuron disease recommended for approval". European Medicines Agency (EMA) (Press release). 23 February 2024. Retrieved 24 February 2024.

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* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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