On February 28, the U.S. Food and Drug Administration (FDA) approved pacritinib (Vonjo) 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 × 109/L. Pacritinib is a novel oral kinase inhibitor with specificity for JAK2 and IRAK1, without inhibiting JAK1, and is the first approved therapy that specifically addresses the needs of patients with cytopenic myelofibrosis.
The accelerated approval is based on efficacy results from the pivotal phase III PERSIST-2 study of pacritinib in patients with myelofibrosis (platelet counts ≤ to 100 × 109/L). Patients were randomly assigned 1:1:1 to receive pacritinib at either 200 mg twice daily, 400 mg once daily, or best available therapy. Prior JAK2 inhibitor therapy was permitted. In this study, in the cohort of patients with baseline platelet counts below 50 × 109/L who were treated with pacritinib at 200 mg twice daily, 29% of patients had a reduction in spleen volume of at least 35% compared to 3% of patients receiving best available therapy, which included ruxolitinib. As part of the accelerated approval, pacritinib’s manufacturer is required to describe a clinical benefit in a confirmatory trial. To fulfill this post-approval requirement, the manufacturer plans to complete the PACIFICA trial, with expected results in mid-2025.
The most common adverse reactions (≥ 20%) following treatment with pacritinib at 200 mg twice daily were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema. The most frequent serious adverse reactions (≥ 3%) were anemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia, and squamous cell carcinoma of the skin.