John Mascarenhas, MD, discusses the mechanism of action of pacritinib and how it differs from ruxolitinib and fedratinib.
John Mascarenhas, MD, professor of medicine at Icahn School of Medicine at Mount Sinai, director of the Center of Excellence for Blood Cancers and Myeloid Disorders, and a member of The Tisch Cancer Institute, discusses the mechanism of action of pacritinib (Vonjo) and how it differs from ruxolitinib (Jakafi) and fedratinib (Inrebic).
On February 28, 2022, the FDA granted approval to pacritinib for the treatment of patients with myelofibrosis and severe thrombocytopenia, defined as a platelet count less than 50x109/L, based on positive results from 3 clinical trials.
According to Mascarenhas, pacritinib targets the JAK/STAT pathway differently than the 2 other FDA-approved JAK inhibitors.
Transcription:
0:07 | So, ruxolitinib is a JAK1/2 inhibitor and fedratinib is a selective JAK2 inhibitor. Pacritinib is a JAK2 selective inhibitor that also inhibits IRAK1, and it is likely that some of these non-JAK receptor kinase inhibition aspects of these drugs likely provide differences both in tolerability and safety but also in efficacy and have the potential to address niches.
0:41 | So, in this case, as a JAK2/IRAK1 inhibitor that down regulates the IL-1 toll like receptor mitogenome NF-κB axis, it also reduces inflammatory cytokines through a nonJAK2-dependent pathway can complement JAK2 inhibition. And it may be for this reason that one can deliver pacritinib at 2 mg twice daily to patients, particularly with thrombocytopenia, that are the hallmark of the cytopenic myelofibrosis patient, and for the spleen and symptoms which we really can't achieve with drugs like ruxolitinib.
Cretostimogene Grenadenorepvec Shows High CR Rate in BCG-Unresponsive NMIBC
July 17th 2024Mark D. Tyson, II, MD, MPH, discussed treatment with cretostimogene grenadenorepvec in high-risk Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer with carcinoma in situ and data from the BOND-003 trial.
Read More
Rossetti Reviews Myelofibrosis Risk Stratification and Outcome Data for Pacritinib
July 17th 2024During a Case-Based Roundtable® event, James M. Rossetti, DO, discussed the role of risk scoring and stratification tools and treatment for a patient with declining hemoglobin and platelet counts due to primary myelofibrosis.
Read More
Phase 3 VERIFY Trial Investigates Rusfertide’s Potential in Polycythemia Vera
July 16th 2024In an interview, Aniket Bankar, MD, discussed the background, design, and goals of the phase 3 VERIFY trial of the hepcidin mimetic rusfertide for the treatment of patients with polycythemia vera.
Read More