Data from a study published in Blood demonstrates the therapeutic potential of INCA033989 as the first targeted therapy for myeloproliferative neoplasms (MPNs) that does not interfere with normal blood cell production. Existing therapeutic options for MPNs are effective at symptom management but have high discontinuation rates due to resistance and inadequate drug tolerability. The development of INCA033989 opens pathways to more effective, targeted options with disease-modifying potential without any negative impact on surrounding blood cells.1
The development of INCA033989 has positive implications for the evolving treatment landscape of patients with MPNs. Image Credit: © Anna – stock.adobe.com
MPNs are a group of malignancies characterized by the overproduction of red and white blood cells and is an umbrella for 6 different disease types: myelofibrosis (MF), essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, chronic neutrophilic leukemia, and chronic eosinophilic leukemia. Calreticulin (CALR) mutations are responsible for disease development in 20% to 30% of patients with MPNs, which can be either insertions or deletions in exon 9 of CALR. The mutated CALRprotein (mutCALR) is responsible for the stable interaction with thrombopoietin receptors (TPO-R), which are crucial for controlling blood cell production.2,3
Janus kinase (JAK) inhibitors, such as ruxolitinib (Jakafi; Incyte Corp), are the recommended treatment options for patients with MF or other MPNs; however, they are associated with adverse effects (AEs), namely grade 3 or 4 anemia. INCA033989 is a high affinity, fully human immunoglobulin G1 selective monoclonal antibody targeting mutCALR-driven oncogenesis to suppress TPO-R signaling, thereby preventing the proliferation and progression of disease. According to data from the original study announcing the development of this agent, there was an observed synergism between INCA033989 and ruxolitinib which resulted in the inhibition of cell proliferation and indicated the ability of INCA033989 to enhance the efficacy of ruxolitinib.3,4