The active ingredient in Vonjo® is pacritinib, a potent oral kinase inhibitor that is highly specific for Janus kinase 2 (JAK2) and interleukin 1 receptor-associated kinase 1 (IRAK1) but does not inhibit JAK1.1 This medication, marketed by CTi BioPharma, is indicated for the treatment of adults who have intermediate- or high-risk primary or secondary myelofibrosis (MF) with a platelet count below 50×109/L. The indication was approved by the US Food and Drug Administration (FDA) in February 2022 under accelerated approval based on spleen volume reduction (SVR).2

Vonjo is the first approved drug that specifically addresses the requirements of patients with cytopenic MF.3

MF is a rare disease characterized by hematologic abnormalities and bone marrow fibrosis. MF can develop de novo (primary MF) or as a result of polycythemia vera (PV) or essential thrombocythemia (ET) as secondary MF. The signs and symptoms of MF result from abnormalities of blood cell production and include cytopenia, infection, splenomegaly, and generalized systemic symptoms.4

Mechanism of Action

The JAK/signal transducer and activator of transcription (STAT) pathway primarily regulates cell proliferation, differentiation, and survival. In MF, constitutive activation of the JAK/STAT pathway is an important driver of disease; most patients have acquired genetic driver mutations for JAK2 (JAK2 V617F in 60%), calreticulin, and/or thrombopoietin receptor (also known as MPL), all of which result in a JAK/STAT-mediated inflammatory cascade and dysregulated hematopoiesis.5

Recent research also links the pathophysiology of MF to other distinct biological factors activated by the Toll-like receptor (TLR)/myddosome/IRAK1 inflammatory pathway. The cytokines involved in this pathway are not suppressed by JAK1/2 inhibition, so that IRAK1 is another important pathway to target in MF, independently of JAK signaling.5,6  

Vonjo inhibition of these 2 distinct pathways, JAK/STAT and Toll-like receptor (TLR)/myddosome/IRAK1, in individuals with MF results in the suppression of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and the downstream inflammatory cytokine cascade, a decrease in spleen size, and symptomatic control.6

Vonjo is a potent kinase inhibitor that is highly specific for JAK2 (JAK2 V617F) and IRAK1. At clinically relevant concentrations, it induces the dose-dependent inhibition of JAK2 (JAK2 V617F) and downstream STAT phosphorylation; however, its effect on JAK1 is negligible. Vonjo is the first and only JAK1-sparing inhibitor that targets both JAK2 and IRAK1.3,6 

JAK1 inhibition is known to reduce megakaryopoiesis and the production of platelets; therefore, the minimal JAK1 inhibitory activity of Vonjo is a factor contributing to the hematologic stability noted with this drug.5,6 

Read more about MF pathophysiology


Vonjo is available as 100-mg capsules. The recommended dosage is 200 mg taken orally 2 times daily,3 either with or without food. Before starting Vonjo, patients undergoing treatment with other kinase inhibitors must taper or stop their current regimen according to Vonjo prescribing information.7 

Get full prescribing information for Vonjo at MPR

Adverse Effects

Regardless of their platelet count, Vonjo has shown an acceptable safety profile in trials of individuals with MF. Hematologic stability is maintained in most patients. Low-grade gastrointestinal toxicities, including diarrhea and nausea, are the most common nonhematologic adverse effects.6

Overall, the most common adverse reactions noted in clinical trials are diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema.2 Other side effects include vomiting, dizziness, pyrexia, epistaxis, dyspnea, pruritus, upper respiratory infections, cough, and serious cardiovascular events.8  

Read more about MF complications

Warnings and Precautions 

Vonjo is contraindicated in patients who are concomitantly taking strong CYP3A4 inhibitors (eg, clarithromycin) or inducers (eg, rifampin) because these medications in combination with Vonjo can increase the risk of adverse reactions or decrease the efficacy of Vonjo. Vonjo should also be avoided in patients with liver or kidney impairment. Patients should not breastfeed while on Vonjo.2 

The most important warnings and precautions regarding the adverse effects of Vonjo are described below.


Because Vonjo increases the risk of hemorrhage, the drug should be avoided in patients with active bleeding and discontinued 7 days before planned elective surgeries or invasive procedures. It should be restarted only if hemostasis is ensured.5 


Preexisting diarrhea should be controlled before Vonjo is initiated. Therapy should be interrupted or reduced if significant diarrhea develops despite adequate supportive care. Anti-diarrheal medications should be administered.2


Because Vonjo use can result in thrombocytopenia, the patient’s platelet counts should be checked before initiating treatment and as clinically indicated during treatment. Therapy should be interrupted if significant worsening thrombocytopenia lasts longer than 7 days.3 

Prolonged QT Interval 

Vonjo can cause prolongation of the QTc interval. The drug should be avoided in patients whose baseline QTc interval is longer than 480 milliseconds. Therapy should be interrupted or reduced in patients with a QTc longer than 500 milliseconds. Hypokalemia before or during the administration of Vonjo should be managed.2 

Major Adverse Cardiac Event (MACE)

Patients taking Vonjo should be monitored for the development of a MACE. Before Vonjo therapy is started, especially if the patient is a current or past smoker or has other cardiovascular risk factors, the advantages and risks of Vonjo administration should be considered. Patients should be educated about the signs and symptoms of significant cardiovascular events and the steps to be taken if these occur.2

Possibility of Thrombosis

If symptoms of thrombosis develop, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, the patient should be evaluated immediately for the initiation of treatment.2 

Risk of Infection

Patients taking Vonjo may be subject to severe bacterial, mycobacterial, fungal, or viral infections. Vonjo therapy should not be started until any active serious infections have resolved. Patients should also be observed while on Vonjo treatment for any clinical manifestations of infection and managed according to clinical guidelines with prophylactic antibiotics.5

Possibility of Secondary Malignancies

Patients on Vonjo should be monitored for the development of secondary malignancies, especially those who are current or past smokers.2

Read more about MF prognosis

Safety and Efficacy in Trials

The safety and efficacy of Vonjo were assessed in 2 phase 3 clinical trials, PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781), and in a phase 2 study, PAC203 (NCT04884191).


PERSIST-1 compared the safety and efficacy of Vonjo with those of best available therapy (BAT) in adults with intermediate- or high-risk primary or secondary MF and no prior JAK2 inhibitor treatment.6

Vonjo at 400 mg daily was associated with durable and significant reductions of splenomegaly when compared with BAT. By week 24, spleen volume reduction (SVR) of 35% or higher had occurred in 19% of patients in the Vonjo arm and 5% of those in the BAT arm. The difference in this SVR outcome remained statistically significant in patients with severe thrombocytopenia: 23% for Vonjo vs 0% for BAT. At week 24, the proportions of patients with a decrease of 50% or more in their total symptom score (TSS) were comparable in the 2 arms. However, by week 48, a decrease in the TSS of 50% or more had occurred in 15% of patients in the Vonjo arm vs 0% in the BAT arm.6


The FDA-accelerated approval of Vonjo was based on results of the phase 3 PERSIST-2 study. PERSIST-2 enrolled patients who had intermediate- or high-risk primary or secondary MF with splenomegaly and a platelet count of 100×109 /L or lower. Both JAK2-naïve patients and patients with prior JAK2 inhibitor therapy were enrolled.4,7

The patients received 200 mg of Vonjo twice daily, 400 mg once daily, or BAT. Among the patients with a baseline platelet count below 50×109/L, 29% of those treated with 200 mg of Vonjo twice daily achieved an SVR of at least 35%, vs 3% of those who received BAT, which included Jakafi® (ruxolitinib). Additionally, 23% of the patients who received 200 mg of Vonjo twice daily achieved a 50% reduction in TSS vs 13% of those who received BAT.4,7


The phase 2 PAC203 study enrolled patients with MF who either could not tolerate or had failed to benefit from Jakafi. Vonjo at 200 mg twice daily was generally well tolerated and demonstrated clinical activity, particularly in patients with severe thrombocytopenia (platelet count <50,000/mL). Vonjo was associated with a reduction in spleen size (SVR ≥35%) and symptom burden (TSS ≥50%) according to precise criteria for frontline response.9


PACIFICA, which is anticipated to conclude in mid-2025, is a randomized phase 3 clinical study (NCT03165734) that is being conducted by CTi BioPharma to compare the efficacy and safety of 200 mg of Vonjo twice daily with those of a physician’s choice of therapy. The participants are adults with primary or secondary MF who are not candidates for stem cell transplant and who meet the following criteria: Dynamic International Prognostic Scoring System (DIPSS) intermediate- or high-risk disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 or lower, and platelet count below 50×109 /L. The patients can have had up to 90 days of prior treatment with a JAK2 inhibitor or can be JAK2 inhibitor-naïve.4,10 

Read more about MF clinical trials


  1. VONJO® (pacritinib). CTi BioPharma. Accessed December 29, 2022.
  2. VONJO™ (pacritinib) capsules, for oral use. Highlights of prescribing information. Revised February 2022. Accessed December 29, 2022.
  3. FDA approves Vonjo. News release. CTi BioPharma; February 28, 2022.
  4. VONJO (pacritinib) to treat myelofibrosis, USA. Clinical Trials Arena. Updated August 23, 2022. Accessed December 29, 2022.
  5. VONJO® (pacritinib) capsules. CTi Biopharma. Accessed December 29, 2022.
  6. Mascarenhas J. Pacritinib for the treatment of patients with myelofibrosis and thrombocytopenia. Expert Rev Hematol. 2022;15(8):671-684. doi:10.1080/17474086.2022.2112565
  7. Vonjo (pacritinib). wcg CenterWatch. Accessed December 29, 2022.
  8. VONJO Rx. MPR. Accessed December 29, 2022.
  9. Gerds AT, Savona MR, Scott BL, et al. Results of PAC203: a randomized phase 2 dose-finding study and determination of the recommended dose of pacritinib. Blood. 134 (2019):667. doi:10.1182/blood-2019-129293
  10. Harrison CN, Gerds AT, Kiladjian J-J, et al. Pacifica: a randomized, controlled phase 3 study of pacritinib vs. physician’s choice in patients with primary myelofibrosis, post polycythemia vera myelofibrosis, or post essential thrombocytopenia myelofibrosis with severe thrombocytopenia (platelet count< 50,000/mL). Blood. 134(2019):4175. doi:10.1182/blood-2019-129245

Reviewed by Hasan Avcu, MD, on 1/4/2023.