Fitusiran Is a Drug to Watch in the Hematology Space in 2025

Clarivate named fitusiran (Alnylam Pharmaceuticals, Sanofi) as a drug to watch in the hematology space for 2025. Fitusiran is part of a generation of novel RNA interference therapies and is designed for subcutaneous administration—either monthly or bimonthly—for the prophylactic treatment of hemophilia A or B, regardless of inhibitor status.¹

These therapies have demonstrated versatile applications across disease states, such as oncology and infectious diseases. | Image Credit: shidlovski | stock.adobe.com

Fitusiran is an antithrombin-targeting small interfering RNA (RNAi) drug. RNAi therapies have the ability to selectively silence or downregulate specific genes for the treatment of many diseases and enhance more personalized and precise treatment approaches. These therapies demonstrated versatile applications across disease states, such as oncology and infectious diseases. However, there are challenges with this class of medication, such as delivery methods, off-target effects, and the potential for activation of the immune system, but the class remains promising in precision therapy treatment.^1,2

Clinical data from phase 3 studies demonstrate the potential of fitusiran, specifically for meaningful reductions in annualized bleeding rates in patients with hemophilia A or B. In one phase 3 clinical trial (NCT03417245), investigators aimed to evaluate the efficacy of the drug compared with on-demand treatment with factor concentrates. The duration of treatment with fitusiran was approximately 9 months, with screening up to 11 months for all patients, regardless of treatment. Investigators estimated that the total time for the study was up to 17 months for those taking fitusiran and did not enroll in the extension study.^1,3

Individuals included were 12 years or older with severe hemophilia A or B without inhibitors. Further, patients had a minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months prior to screening. Secondary objectives of the study included the frequency of spontaneous bleeding episodes, frequency of joint bleeding episodes, health-related quality of life for those 17 and older, frequency of bleeding episodes during the onset period, and to determine the safety and tolerability of fitusiran.³

Between March 1, 2018, and July 14, 2021, 120 patients were assigned randomized treatment with either fitusiran (n = 80) or on-demand clotting factor concentrates (n = 40), with a median follow-up of 7.8 months for both groups. In the fitusiran group, the mean annualized bleeding rate was 0.0 and 21.8 in the on-demand factor group. Furthermore, 51% of those in the fitusiran group had no treated bleeds compared with 5% in the on-demand factor group. The most common treatment-emergent adverse event included increased alanine aminotransferase concentrations in the fitusiran group (23%) and hypertension in the on-demand factor group (10%). Serious AEs were reported in 6% of those in the fitusirangroup and 13% in the on-demand factor group.⁴

In another study (NCT03417102), investigators aimed to further determine the frequency of bleeding episodes compared with on-demand treatment. The population was generally the same as with the previous study and had similar end points. Between February 14, 2018, and June 23, 2021, 57 individuals were included in the study, with 19 receiving the on-demand agent and 38 receiving fitusiran. The annualized bleeding rate was significantly lower in the fitusiran group compared with the on-demand group, showing an approximate reduction of 90.8% in annualized bleeding rate. Approximately 66% of individuals had 0 treated bleeds compared with 1 in the on-demand group. The most frequent AEs included increased alanine aminotransferase for 32% of the individuals in the fitusiran group, and there was no increased alanine aminotransferase in the on-demand group.^5,6

Pharmacists play a large role in the management of hemophilia A and B for patients, especially due to the unpredictability of bleeding. Due to this, patients need to be consistently monitored, which make pharmacists a first point-of-contact for patients as they can spot symptoms. For treatment, pharmacists can collaborate with other members of the care team to help manage various bleeding disorders. Pharmacists are the medication experts, so they can counsel and advise on which treatment may work best for each patient to help personalize the treatment experience.⁷

REFERENCES

1. Halpern L. Key Drugs to Watch in Oncology, Hematology, and Neurology for 2025. Pharmacy Times. January 17, 2025. Accessed January 29, 2025. https://www.pharmacytimes.com/view/key-drugs-to-watch-in-oncology-hematology-and-neurology-for-2025

2. Dymala K. The Promise of RNA Interference (RNAi) Therapies: Revolutionizing Medicine. Pharmacy Times. May 9, 2024. Accessed January 29, 2025. https://www.pharmacytimes.com/view/the-promise-of-rna-interference-rnai-therapies-revolutionizing-medicine

3. A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors. ClinicalTrials.gov identification: NCT03417245. Updated March 28, 2022. Accessed January 29, 2025. https://clinicaltrials.gov/study/NCT03417245

4. Srivastava A, Rangarajan S, Kavakli K, et al. 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. 2023;10(5):e322-e332. doi:10.1016/S2352-3026(23)00037-6

5. A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients With Inhibitors (ATLAS-INH). ClinicalTrials.gov identification: NCT03417102. Updated March 28, 2022. Accessed January 29, 2025. https://clinicaltrials.gov/study/NCT03417102

6. Young G, Srivastava A, Kavakli K, et al. 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. 2023;401(10386):1427-1437. doi:10.1016/S0140-6736(23)00284-2

7. Halpern L. Proper Dosing, Bleeding Awareness Essential Roles of Pharmacists for Hemophila A and B, Thrombocytopenic Purpura Treatment. Pharmacy Times. January 21, 2025. Accessed January 29, 2025. https://www.pharmacytimes.com/view/proper-dosing-bleeding-awareness-essential-roles-of-pharmacists-for-hemophila-a-and-b-thombocytopenic-purpura-treatment