Selective JAK inhibitors received FDA priority review for the treatment of myelofibrosis

On June 1, 2021, CTI Biopharma announced that the U.S. Food and Drug Administration has accepted its New Drug Application (NDA) for pacritinib, an oral kinase inhibitor in the pipeline, to treat myelofibrosis, a disease associated with severe thrombocytopenia. The FDA also granted priority review status to the NDA, with a response expected by November 30.

Pacritinib is an oral inhibitor that specifically inhibs JAK2, IRAK1, and CSF1R. One of its features is that it does not inhibit JAK1 activity, thus avoiding the potential side effects of inhibiting JAK1. The JAK family of proteins are central components of a variety of signal transduction pathways that are critical for normal blood cell growth and development, as well as for the expression of inflammatory cytokines and immune responses. Mutations in these kinases have been shown to be directly associated with the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. In addition to myeloid fibrosis, pacritinib has potential therapeutic effects in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myeloid mononuclear leukemia (CMML) and chronic lymphoblastic leukemia (CLL).

This NDA application is based on positive results from one phase 2 clinical trial and two phase 3 clinical trials of pacritinib. The results showed that 29 percent of patients treated with pacritinib had a reduction in spleen volume of at least 35 percent, compared with only 3 percent in the active control group. In addition, 23 percent of patients had at least a 50 percent reduction in their overall symptom score, compared with only a 13 percent reduction in the active control group. In terms of safety and drug resistance, adverse events are usually low-level, manageable with supportive care, and rarely lead to drug withdrawal. Platelet counts and hemoglobin levels also remained stable.

Molecular formula for Pacritinib

Myelofibrosis is a type of bone marrow cancer characterized by the formation of fibrous scar tissue that can lead to severe thrombocytopenia and anemia, weakness, fatigue, and enlargement of the spleen and liver. It is estimated that patients with severe thrombocytopenia account for one-third of patients receiving myelofibrosis treatment, with an overall survival of only 15 months.