How Divesiran Works
Divesiran is a first-in-class siRNA (short interfering RNA) therapy in development for polycythemia vera (PV). PV is a myeloproliferative neoplasm characterized by the overproduction of red blood cells (RBCs). Elevated hematocrit (HCT) - an index of RBC mass - is a hallmark of the disease. HCT levels above 45% increases risk of thrombotic and cardiovascular events.
Divesiran works by "silencing" the TMPRSS6 gene, lifting the natural brake on hepcidin - the body's master iron regulator. When TMPRSS6 is turned down, hepcidin levels rise, reducing iron availability to the bone marrow. With less iron, the overproduction of red blood cells seen in PV is reduced. This helps keep HCT levels in a safer range and can reduce or eliminate the need for phlebotomies. Additionally, siRNA therapies have a highly potent and durable effect - enabling less frequent and more convenient dosing.