Date: 2014-12-06
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition held December 6-9 in San Francisco, CA.
Company: CTI BioPharma - previously known as Cell Therapeutics (USA - WA)
Product: pacritinib
Action mechanism: tyrosine kinase inhibitor. Pacritinib is a next generation oral multikinase inhibitor with activity against JAK2 and FLT3, as well as other kinases. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. Pacritinib may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anemia than has been seen in currently approved and in-development JAK inhibitors. In November 2013, CTI and Baxter entered into a worldwide license agreement to develop and commercialize pacritinib. Under this agreement, CTI and Baxter will jointly commercialize pacritinib in the U.S., while Baxter has exclusive commercialization rights for all indications outside the U.S.
Disease: myelofibrosis
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest news: • On December 6, 2014, CTI BioPharma announced that an analysis of kinase inhibition by pacritinib demonstrated a unique kinome profile among agents in development for myelofibrosis and suggests potential therapeutic benefit across a spectrum of blood-related cancers. Researchers presented the findings from this analysis at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition held December 6-9 in San Francisco, CA. The in vitro profiling of pacritinib across a panel of kinases showed the inhibition of all members of the JAK/FLT pathways, with the exception of JAK1. The JAK/FLT pathways are frequently dysregulated in many types of cancers. Additionally, pacritinib was found to inhibit the kinases c-fms and IRAK1. Disruption in the c-fms and IRAK1 pathways have been indicated to be involved in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and chronic lymphocytic leukemia (CLL). CTI believes the clinical efficacy and reduced myelosuppression seen in Phase 2 trials of pacritinib in patients with myelofibrosis is also likely attributable to this unique kinase inhibition profile. The analysis was conducted to develop a comprehensive kinase profile of pacritinib and elucidate a potential mechanism for its lack of myelosuppression as seen in clinical trials. The kinome screening analysis was done against a 429 member kinase panel and demonstrated the inhibition of all members of the JAK/FLT pathways at low nanomolar concentrations (e.g., JAK2 IC50 = 6.0 nM, FLT3 IC50 = 14.8 nM) with the exception of JAK1, against which pacritinib was completely inactive at 100nM. Additionally, pacritinib was a potent inhibitor of other tyrosine kinases of interest, including c-fms (IC50 = 39.5 nM) and other non-tyrosine kinases such as IRAK1 (IC50 = 13.6 nM). The results showed that pacritinib has an unusual spectrum of activity compared to other JAK inhibitors, combining lack of suppression of JAK1 with suppression of inflammatory signaling through c-fms and IRAK1. (Comprehensive Kinase Profile of Pacritinib, a Non-Myelosuppressive JAK2 Kinase Inhibitor in Phase 3 Development in Primary and Post ET/PV Myelofibrosis)
