World Health Organization (WHO) classification of myeloproliferative neoplasms (MPN) including chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF) and essential thrombocythemia (ET). These neoplasms are characterized by the clonal proliferation of one or more hematopoietic cell lineages, predominantly in the bone marrow, but sometimes in the liver and spleen. Essential thrombocythemia (ET) is a chronic MPN previously called hemorrhagic thrombocythemia, is characterized by a sustained clonal proliferation of megakaryocytes in the bone marrow. The proliferation of megakaryocytes is primarily caused by clonal stem cells, as confirmed by enzyme and genetic analysis. Janus kinase 2 (JAK2) is an intracellular non-receptor tyrosine kinase that plays an essential role in normal hematopoiesis. And, Calreticulin (CALR) is a multifunctional protein that acts as a major Ca-binding protein in the endoplasmic reticulum (ER). Recently identified JAK2 V617F mutation and the exon 9 of CALR gene mutation are associated with ET. Among ET patients, JAK2 V617F mutation is about 60-65% and CALR mutation is about 20-25%. Reported annual incidence rates for ET have ranged from 0.59 to 2.53/100,000 inhabitants and the prevalence is 30/100,000 inhabitants in Western countries. The incidence is higher in females compared with males and the median age at diagnosis is 65 to 70 years.
Patients suffering from ET are at high risk for developing thrombosis or bleeding and significant disease-related symptom including headaches, fatigue, pruritus and erythromelalgia. Therapeutic options for ET patients range from the most conservative approach to cytoreductive drugs. The general consensus on the use of a risk-adapted strategy in treatment of ET patients. As a first step in disease management, ET patients should have an assessment of their risk factors. The risk factors contain age, history of thrombosis and platelet count. Hydroxyurea (HU) is generally considered the first-line therapy for ET. HU is very effective in reducing platelet numbers and is used to control platelets in patients. However, many patients do not tolerate HU or suffer from anemia, leukopenia, skin lesions, or gastrointestinal symptoms. For ET patients resistant or intolerant to HU, interferon alpha (INF-α), busulfan, anagrelide and ruxolitinib are considered as the second-line therapy.
INF-α has a long history in management of ET related thrombocytosis/leukocytosis, reduction in JA2V617F allele burden, control of vascular diseases, and decreases ET-related symptoms. In addition, INF-α has shown potential for delaying progression of ET by reduction of clonal burden. Recent reports also demonstrated that the role of interferon alpha (INF-α) on the allelic burden of the CALR and JAK2 V617F mutation in post-treatment follow-up period. It is worth noting that true effectiveness of pegylated IFN-α in treating ET is still unknown. PharmaEssentia Corporation is developing Ropeginterferon alfa-2b (P1101) for the treatment of ET with an injection duration every two weeks and making a great effort to achieve much better tolerated and compliance, leading to improved response rates .