Givinostat + hydroxyurea

Givinostat + hydroxyurea is a combination of two pharmaceutical agents being studied for the treatment of polycythemia vera (PV), a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by excessive production of blood cells and commonly associated with the JAK2 V617F mutation. Givinostat is an orally bioavailable, potent inhibitor of class I and II histone deacetylases (HDACs) that exhibits antineoplastic activity by decreasing JAK2/STAT5 phosphorylation, attenuating JAK2/STAT5 signaling, and inducing apoptosis in JAK2 V617F-positive cell lines. Hydroxyurea is a well-established cytoreductive agent used as standard first-line therapy for PV. The combination or comparison of these drugs is under investigation in clinical trials to assess efficacy and safety in high-risk PV patients[1][3][4][5]. Givinostat has shown promising results in reducing disease symptoms, normalizing hematological parameters, lowering thrombotic risk compared to historical controls treated with hydroxyurea or phlebotomy, and maintaining durable responses over several years[2][8].