Polycythemia Vera overview
Polycythemia Vera (PV) is a rare myeloproliferative neoplasm characterized primarily by the overproduction of red blood cells. PV is typically caused by a form of Janus Kinase 2 (JAK2) mutation. PV is a serious chronic condition as the increased red blood cell count 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: to control the patient’s hematocrit (red blood cells as a percentage of whole blood) below 45% in order to reduce the risk of further cardiovascular or thrombotic events. PV may progress to myelofibrosis of leukemia.
Currently 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 (Jakafi). Jakafi is currently the only branded product in the US for PV. Cytoreductive therapies such as hydroxyurea, interferons and ruxolitinib can have challenging side effect profiles as they reduce all cell types. Current treatments are effective in some patients, but we believe there are substantial patient groups that could benefit from a new non-cytoreductive therapeutic option.
Hereditary Hemochromatosis overview
Hereditary hemochromatosis (HH) is caused by genetic mutations that leads to hyperabsorption of iron from the diet and alters its distribution in the body, leading to iron buildup in the liver, heart and other organs. Too much iron can be toxic and over time can lead to cirrhosis and cancer, heart problems, skin lesions, joint pain and diabetes. The genetic defect that causes most HH originates in northern Europe, and there are approximately 5-7 million people with this defect in the US and EU.
PV market overview
There are approximately 160,000 patients living with PV in the United States, with a similar prevalence in Europe. Approximately 15,000 new patients have been diagnosed each year since 2017. Patients are typically diagnosed between the age 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 does not offer adequate hematocrit control below 45%. In fact, less than 30% of patients in our data set had all hematocrit test results under 45%; indicating that as many as 70,000 patients in the US alone may be at elevated risk of cardiovascular and thrombotic events.
We believe that PTG-300 has the potential to provide substantial benefit to patients by providing a tool focused entirely on managing hematocrit in a consistent and predictable manner. PTG-300 is a non-cytoreductive, first-in-class, mimetic of the natural hormone hepcidin, the master regulator of iron homeostasis in the body. PTG-300 has a unique iron regulatory mechanism which allows for persistent control of hematocrit without causing iron deficiency. It acts by redistributing iron away from the bone marrow where iron is in high demand and essential for red blood cell production, thereby limiting excess red blood cell production in patients with polycythemia vera.