Vonjo (pacritinib)

He was started on JAK inhibitor therapy with pacritinib but clinically declined over the next several days with worsening diffuse pain and pancytopenia...Shortly after, the patient presented to an outside hospital with septic shock, at which point the patient expired. This case illustrates the aggressive nature of the disease, the need for confirmatory testing when diagnosis is suspected and the difficulty in management as the prognosis is poor and requires aggressive treatment that can lead to life-threatening sequelae.

P2, N=32, Not yet recruiting, Medical College of Wisconsin

Adverse events, including gastrointestinal symptoms, weight loss, and transient voice changes, were manageable through dose adjustments and supportive care, enabling continued therapy. Our cases contribute to the growing body of evidence supporting pacritinib's role in the evolving treatment landscape of MF.

Notably, we found that gastric cancer cells display marked sensitivity to IRAK1/4 inhibitor and pacritinib, the latter targeting JAK2 and IRAK1 specifically, over the pan-JAK inhibitor tofacitinib. Collectively, our results underscore IRAK1 as a promising therapeutic target in gastric cancer. Furthermore, the pharmacological blockade of IRAK1 by pacritinib, an established drug for myelofibrosis and severe thrombocytopenia treatment, holds potential for repurposing in gastric cancer therapy.

Post-molecular dynamics simulation MM-GBSA analysis further confirmed these interactions, with binding free energies for FLT3: Kaempferol (-73.75 kcal/mol), Apigenin (-68.76 kcal/mol), Pacritinib (-51.27 kcal/mol); and for PIM1: Tricetin (-64.28 kcal/mol), Diosmetin (-52.2 kcal/mol), SEL24 (-53.38 kcal/mol). FLT3 and MPO were identified as specific diagnostic and prognostic biomarkers for AML. This comprehensive in-silico analysis revealed promising therapeutic compounds from E. prostrata targeting FLT3 and PIM1, along with novel biomarker potentials of FLT3 and MPO for improved AML diagnosis and prognosis, subject to further experimental validation.

P1/2, N=74, Active, not recruiting, National University Hospital, Singapore | Recruiting --> Active, not recruiting | Trial completion date: Jul 2023 --> Jul 2026 | Trial primary completion date: Jul 2023 --> Jul 2026

P1, N=10, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Nov 2026 --> Mar 2028 | Trial primary completion date: Nov 2026 --> Mar 2028

In the dacarbazine-sensitive melanoma model, the combination of pacritinib and dacarbazine is more effective than dacarbazine alone in reducing tumor growth and improving overall survival in mice. In summary, our findings highlight IRAK1 as a promising therapeutic target to overcome melanoma resistance, and pacritinib emerges as a valuable addition to the treatment armamentarium for melanoma.

P2, N=30, Recruiting, Shayna Sarosiek, MD | Not yet recruiting --> Recruiting

P2, N=27, Not yet recruiting, University of Washington

In PV, ropeginterferon alfa-2b has shown potential disease-modifying effects by reducing the JAK2 V617F allele burden. For ET, treatment remains focused on thrombosis prevention, with hydroxyurea as the mainstay, and novel agents such as pegylated interferon and bomedemstat (LSD1 inhibitor) are also under development. In MF, the evolution of JAK inhibitors is particularly noteworthy, with momelotinib and pacritinib showing potential benefits in alleviating anemia. Additionally, now that HemeSight® is covered by Japanese national health insurance, genetic mutation analysis has become more accessible, paving the way for risk classification based on genetic profiling. This review provides a comprehensive update on the latest risk stratification and therapeutic strategies for MPNs, highlighting emerging treatments and their potential impact on disease management.