Polycythemia Vera (PV) Overview
PV is a rare myeloproliferative neoplasm characterized primarily by the overproduction of RBCs. The main underlying cause of PV is a mutation in the Janus Kinase 2 (JAK2). PV is a serious chronic condition of increased RBC count, which causes the blood to thicken and puts patients at higher risk of cardiovascular and thrombotic events such as heart attack and stroke. Patients are typically stratified as low or high risk based on age and medical history. Regardless of risk categorization, treatment guidelines for PV are consistent in their recommendation to control the patient’s hematocrit (RBCs as a percentage of whole blood) below 45% in order to reduce the risk of further cardiovascular or thrombotic events. PV is a slow progressive disease with an average span of about 20 years and may ultimately progress to myelofibrosis or leukemia.
Currently, PV patients are typically treated with low-dose aspirin and phlebotomy alone or hydroxyurea alone or in combination with phlebotomy. At later stages, patients may receive interferons or ruxolitinib, marketed as Jakafi®; the latter currently being the only branded product in the U.S. approved for PV. There has been only one FDA-approved treatment for PV in the past 12 years. Cytoreductive therapies such as hydroxyurea, interferons, and ruxolitinib can have challenging side effect profiles as they reduce all cell types, not specifically RBCs. Current treatments are effective in some patients, but we believe there are many patients who could benefit from a new non-cytoreductive therapeutic option.
Polycythemia Vera (PV) Market Overview
PV is a rare disease affecting approximately 160,000 patients in the U.S., with a similar prevalence in Europe, representing an estimated market opportunity of approximately $1.0 billion to $2.0 billion. Since 2017, approximately 14,000 new patients have been diagnosed with PV each year since.
Patients are typically diagnosed between the ages of 50 and 70 and median survival is approximately 20 years. Recent analysis of patient data from a large medical claims database indicates that the current treatment paradigm consists primarily of therapeutic phlebotomy, hydroxyurea, or a combination of hydroxyurea and phlebotomy. According to the analysis of the large data claims database, current therapies do not offer adequate hematocrit control below 45% as recommended in the NCCN Guidelines®. In fact, less than 25% of patients in our data set had all hematocrit test results under 45%, indicating that as many as 70,000 patients in the U.S. may be at elevated risk of cardiovascular and thrombotic events.
We believe that rusfertide has the potential to provide substantial benefit to patients by providing a tool focused on managing hematocrit in a consistent and predictable manner and dramatically decreasing the need for therapeutic phlebotomy. Rusfertide is a non-cytoreductive mimetic of the natural hormone hepcidin, the master regulator of iron homeostasis in the body. Rusfertide has a unique iron regulatory mechanism which, per early results from our ongoing Phase 2 study in PV, allows for persistent control of hematocrit without causing iron deficiency. Rusfertide controls iron metabolism by 1) preventing iron absorption in the small intestine and 2) redistribution of iron from the blood to the macrophage storage sites in certain organs and tissues leading to a restoration of an appropriate iron balance throughout the body. Specifically in PV, rusfertide appears to control RBC production by regulating the amount of iron available to the bone marrow for hemoglobin and RBC synthesis.