Sapablursen – Antisense Oligonucleotide Targeting TMPRSS6
Polycythemia vera
Why This Disease Focus?
- Polycythemia Vera (PV) is a type of myeloproliferative neoplasm caused by an acquired mutation in the Janus kinase 2 (JAK2) gene. It is a rare and potentially life-threatening hematologic disease characterized by an overproduction of red blood cells, or erythrocytosis, elevated hematocrit, and an increased risk of thrombosis.1,2 PV is also associated with low levels of hepcidin, the master iron-regulating hormone, which leads to increased iron release and absorption, further contributing to erythrocytosis and the risk of thrombotic events.3
- Patients with PV experience substantial disease burden and morbidity, primarily driven by risk of thrombotic complications, including cardiovascular disease, and disease progression, which may negatively impact overall survival.1,4 Achieving and maintaining hematocrit levels below 45% is a primary therapeutic goal to reduce the incidence of thrombotic events. Although phlebotomy is a standard treatment, many patients struggle to maintain hematocrit below 45%, and phlebotomy often does not adequately alleviate symptom burden. It may even worsen some symptoms, such as fatigue.5,6
About This Program
Sapablursen (ISIS 702843, ONO-0530) is a liver-targeted, ligand-conjugated antisense oligonucleotide inhibitor of transmembrane serine protease 6 (TMPRSS6), which acts as a negative regulator of hepcidin. Sapablursen is an investigational drug being evaluated for its potential to enhance hepcidin production and decrease iron availability for erythropoiesis, which may help reduce the risk of thrombotic events and improve quality of life in patients with phlebotomy-dependent PV.
Sapablursen is currently being investigated in a Phase 3 study to evaluate the safety and efficacy of sapablursen with standard of care in patients with PV who are phlebotomy-dependent.
To learn more about this study, click here.
Sapablursen is under license agreement from Ionis Pharmaceuticals to Ono Pharma and its affiliates.
References
1 Grunwald MR, et al. Clin Lymphoma Myeloma Leuk. 2019;19(9):579-84.
2Marchioli R, et al. N Engl J Med. 2013;368(1):22-33.
3Ganz T, et al. Adv Ther. 2023;40(4):1317-33.
4Tefferi A, et al. Leukemia. 2013;27(9):1874-81.
5Ginzburg YZ, et al. Leukemia. 2018;32(10):2105-16.
6Verstovsek S, et al. Ann Hematol. 2023;102(3):571-81.