Ropeginterferon alfa-2b

Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis. PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, JAK2 V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in JAK2 may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) in vitro.

Interferon alfa-2b has been used for decades in PV despite the lack of formal approval. Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling. The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells. Interestingly, in vitro studies have revealed that ropeginterferon alfa-2b is specific to some extent for JAK2-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials. Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.