General Information

Vonjo (pacritinib) is a novel oral kinase inhibitor with specificity for JAK2 and IRAK1, without inhibiting JAK1.

Vonjo is specifically indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) with a platelet count below 50 × 109 /L.

• This indication was approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Vonjo is supplied as capsules for oral administration. The recommended dosage of Vonjo is 200 mg orally twice daily. Vonjo may be taken with or without food. Swallow capsules whole. Do not open, break, or chew capsules. Patients who are on treatment with other kinase inhibitors before the initiation of Vonjo must taper or discontinue according to the prescribing information for that drug.

Mechanism of Action

Vonjo (pacritinib) is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. MF is often associated with dysregulated JAK2 signaling. Pacritinib has higher inhibitory activity for JAK2 compared to JAK3 and TYK2. At clinically relevant concentrations, pacritinib does not inhibit JAK1. Pacritinib exhibits inhibitory activity against additional cellular kinases (such as CSF1R and IRAK1) the clinical relevance of which is unknown.

Side Effects

Adverse effects associated with the use of Vonjo may include, but are not limited to, the following:

• diarrhea
• thrombocytopenia
• nausea
• anemia
• peripheral edema

Clinical Trial Results

The FDA granted accelerated approval to Vonjo based on efficacy results from the pivotal Phase 3 PERSIST-2 study in patients with myelofibrosis (platelet counts less than or equal to 100 × 109/L). Patients were randomized 1:1:1 to receive Vonjo 200 mg twice daily (BID), Vonjo 400 mg once daily (QD) or best available therapy (BAT). 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 200 mg BD, 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.