Pacritinib (Vonjo®) is 4 times more potent than momelotinib in inhibiting the hepcidin regulator activin A receptor type 1 (ACVR1), according to a new study published in the journal Blood Advances. The treatment is also associated with a significant increase in red blood cell transfusion independence in patients with cytopenic myelofibrosis (MF).

Results, from a phase 3 clinical trial that evaluated the safety and efficacy of oral pacritinib compared to the best available therapy in patients with thrombocytopenia and primary or secondary MF, showed that the treatment was associated with anemia benefit, the researchers noted.

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However, the effect of the treatment on transfusion independence and its mechanism of action in improving anemia has not been studied, they added.

Here, a team of researchers assessed the relative inhibitory potency of pacritinib compared to other janus kinase 2 (JAK2) inhibitors.

They found that pacritinib inhibited ACVR1 with greater potency than fedratinib, momelotinib, or ruxolitinib. 

This inhibitory effect was supported by the inhibition of downstream SMAD signaling together with the suppression of hepcidin production.

In patients who took part in the phase 3 trial and who were not transfusion independent at the start of the trial, a significantly greater proportion of those treated with pacritinib became so compared to patients given best available therapy. 

Moreover, significantly more patients treated with pacritinib had at least a 50% reduction in transfusion burden.

“These data indicate that the anemia benefit of pacritinib may be a function of potent ACVR1 inhibition,” the researchers concluded.

Pacritinib is a potent oral kinase inhibitor that is highly specific for JAK2 and interleukin 1 receptor-associated kinase 1. It was approved by the US Food and Drug Administration in February 2022 for adults with intermediate-risk or high-risk primary or secondary MF with a platelet count below 50×109/L.


Oh ST, Mesa RA, Harrison CN, et al. Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. Blood Adv. Published online August 8, 2023. doi:10.1182/bloodadvances.2023010151

Pacritinib versus best available therapy to treat patients with myelofibrosis and thrombocytopenia (PAC326). US National Library of Medicine. Last updated November 18, 2021. Accessed August 21, 2023.