The JAK family of enzymes are a central component of cell signal transduction pathways. These pathways are critical for normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in the signal transduction kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms (such as myelofibrosis), leukemia and lymphoma.
The kinase profile of pacritinib suggests its potential therapeutic utility not only in myelofibrosis, but also in conditions such as graft versus host disease, acute myeloid leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and chronic lymphocytic leukemia.
Pacritinib for Myelofibrosis
The U.S Food and Drug Administration has approved VONJO™ (pacritinib) in the U.S. for adults with myelofibrosis with a platelet count below 50 x 109/L.
Pacritinib (VONJO™) received accelerated approval in February 2022 for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 x 109/L.
Pacritinib for Other Indications
Graft Versus Host Disease
The combination of pacritinib with the mTOR inhibitor has been shown to effectively suppress donor T cell co-stimulation and IL-6 signal transduction implicated in acute GVHD, while sparing STAT5 activation critical for immune tolerance and donor anti-leukemia immunity1. Learn more.
To test the use of pacritinib in an mTOR inhibitor combination, an investigator-sponsored, single-arm Phase 1/2 study (NCT02891603) is being conducted at the Moffit Cancer Center and the University of Minnesota which is evaluating pacritinib in combination with sirolimus and low-dose tacrolimus, standard immune suppressive medications, for the prevention of acute graft versus host disease (GvHD) after matched-related and unrelated allogeneic hematopoietic cell transplantation (alloHCT). Learn more.