fitusiran

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Ligands
fitusiran

GtoPdb Ligand ID: 13630

Synonyms: ALN-57213 | ALN-AT3 | ALN-AT3SC

Comment: Fitusiran is a small interference RNA (siRNA) class agent. It is intended to reduce the antithrombin (SERPINC1) protein level as a mechanism to promote thrombin synthesis and rebalance hemostasis (and prevent bleeds) in patients with hemophilia A or B [4-5].
GalNAc-conjugation is a strategy used to promote delivery of the drug to the liver [2]- this is annotated as 'R1' in the sequence provided here. We have been unable to locate a full chemical SMILES for the ligand, or its HELM notation.

References
1. Boyce S, Rangarajan S. (2023) RNAi for the Treatment of People with Hemophilia: Current Evidence and Patient Selection. J Blood Med, 14: 317-327. [PMID:37123985]
2. Holm A, Løvendorf MB, Kauppinen S. (2021) Development of siRNA Therapeutics for the Treatment of Liver Diseases. Methods Mol Biol, 2282: 57-75. [PMID:33928570]
3. Kenet G, Nolan B, Zulfikar B, Antmen B, Kampmann P, Matsushita T, You CW, Vilchevska K, Bagot CN, Sharif A et al.. (2024) Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial. Blood, 143 (22): 2256-2269. [PMID:38452197]
4. Machin N, Ragni MV. (2018) An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B. J Blood Med, 9: 135-140. [PMID:30174468]
5. Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, Bevan D, Austin S, Hay CR, Hegemann I et al.. (2017) Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy. N Engl J Med, 377 (9): 819-828. [PMID:28691885]
6. Peyvandi F, Garagiola I, Abbattista M. (2023) Fitusiran in haemophilia: a breakthrough drug with many unknowns. Lancet, 401 (10386): 1400-1401. [PMID:37003290]
7. Srivastava A, Rangarajan S, Kavakli K, Klamroth R, Kenet G, Khoo L, You CW, Xu W, Malan N, Frenzel L et al.. (2023) Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial. Lancet Haematol, 10 (5): e322-e332. [PMID:37003278]
8. Young G, Lenting PJ, Croteau SE, Nolan B, Srivastava A. (2023) Antithrombin lowering in hemophilia: a closer look at fitusiran. Res Pract Thromb Haemost, 7 (4): 100179. [PMID:37358958]
9. Young G, Srivastava A, Kavakli K, Ross C, Sathar J, You CW, Tran H, Sun J, Wu R, Poloskey S et al.. (2023) Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial. Lancet, 401 (10386): 1427-1437. [PMID:37003287]

References

1. Boyce S, Rangarajan S. (2023)
RNAi for the Treatment of People with Hemophilia: Current Evidence and Patient Selection.
J Blood Med, 14: 317-327. [PMID:37123985]

2. Holm A, Løvendorf MB, Kauppinen S. (2021)
Development of siRNA Therapeutics for the Treatment of Liver Diseases.
Methods Mol Biol, 2282: 57-75. [PMID:33928570]

3. Kenet G, Nolan B, Zulfikar B, Antmen B, Kampmann P, Matsushita T, You CW, Vilchevska K, Bagot CN, Sharif A et al.. (2024)
Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial.
Blood, 143 (22): 2256-2269. [PMID:38452197]

4. Machin N, Ragni MV. (2018)
An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B.
J Blood Med, 9: 135-140. [PMID:30174468]

5. Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, Bevan D, Austin S, Hay CR, Hegemann I et al.. (2017)
Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy.
N Engl J Med, 377 (9): 819-828. [PMID:28691885]

6. Peyvandi F, Garagiola I, Abbattista M. (2023)
Fitusiran in haemophilia: a breakthrough drug with many unknowns.
Lancet, 401 (10386): 1400-1401. [PMID:37003290]

7. Srivastava A, Rangarajan S, Kavakli K, Klamroth R, Kenet G, Khoo L, You CW, Xu W, Malan N, Frenzel L et al.. (2023)
Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial.
Lancet Haematol, 10 (5): e322-e332. [PMID:37003278]

8. Young G, Lenting PJ, Croteau SE, Nolan B, Srivastava A. (2023)
Antithrombin lowering in hemophilia: a closer look at fitusiran.
Res Pract Thromb Haemost, 7 (4): 100179. [PMID:37358958]

9. Young G, Srivastava A, Kavakli K, Ross C, Sathar J, You CW, Tran H, Sun J, Wu R, Poloskey S et al.. (2023)
Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial.
Lancet, 401 (10386): 1427-1437. [PMID:37003287]