FDA Approves Pacritinib for Patients with Myelofibrosis and Severe Thrombocytopenia


The FDA has approved pacritinib for the treatment of patients with myelofibrosis and severe thrombocytopenia.

The FDA has approved pacritinib (Vonjo) for the treatment of patients with myelofibrosis and severe thrombocytopenia, defined as a platelet count less than 50x109/L, according to a press release issued by CTI BioPharma Corp.1

"Today's approval of Vonjo establishes a new standard of care for myelofibrosis patients suffering from cytopenic myelofibrosis," said John Mascarenhas, MD, associate professor, Medicine, Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "Myelofibrosis with severe thrombocytopenia, defined as blood platelet counts below 50 × 109/L, has been shown to result in poor survival outcomes coupled with debilitating symptoms. Limited treatment options have rendered this disease as an area of urgent unmet medical need. I am pleased to see that a new, efficacious and safe treatment option is now available for these patients."

Pacritinib is an oral macrocyclic Janus kinase inhibitor specifically used to inhibit JAK2, IRAK1, and CSFIR. The JAK family of enzymes promotes normal blood cell growth in patients because JAK is central component in signal transaction pathways. A direct relationship between mutations in these pathways and the development of hematological cancers like myeloproliferative neoplasms, leukemia, and lymphoma has been found by clinicians. Moreover, due to pacritinib’sinhibition of c-fms, IRAK1, JAK2, and FLT3, the agent may be useful for the treatment of acute myeloid leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and chronic lymphocytic leukemia.

“It is an oral drug that's been in clinical testing now for a number of years, mostly in myelofibrosis, and was recognized early on in clinical development to be a potent JAK2 inhibitor that spares a lot of themylosuppressive effects of inhibiting JAK2 and associated JAK1,” said

John Mascarenhas, MD, an associate professor of Medicine at Mount Sinai in an interview with Targeted Oncology.

The agency approved the agent based off the results of the phase 3 PERSIST-1 (NCT01773187), the phase 3 PERSIST-2 (NCT02055781), and phase2 dose-finding PAC203 trial.

PERSIST-1 looked at 327 patients with myelofibrosis who either received pacritinib or the best available therapy.2 By week 24 of the study, researchers found that 19% of patients in the pacritinibarm achieved the primary endpoint of spleen reduction size by 35% or more, compared to 5% in the control group. Moreover, 90 patients in the control group were switched to pacritinib at a median of 6.3 months on the trial.

PERSIST-1 led to PERSIST-2 which enrolled 311 participants with myelofibrosis who also had thrombocytopenia, and the primary endpoint of the study was to compare efficacy of pacritinib to the best available therapy.3 Patients were divided into 3 arms; in arm 1, patients received pacritinib once daily; in arm 2, patients received pacritinib twice daily; and in arm 3, patients received the best available therapy. 

Twice a day pacritinib was associated with better outcomes compared to patients on the best available therapy. Eighteen percent of patients in the twice-daily pacritinib arm had a spleen reduction of 35% or greater compared to 3% of patients on the best available therapy.

In the PAC203 trial an estimated 348 patients have been enrolled and were randomized to receive 200 mg of the approved agent compared to the physician’s choice of therapy.4 Fifty-four 54 patients received 200 mg of pacritinib twice daily and 5 saw a reduction of spleen size. Fifty-five patients who received 100 mg twice per day and 1 patient saw a reduction in spleen size compared to those who received the same amount once daily none saw a reduction in spleen size.

In terms of safety, the most common adverse reactions (≥ 20%) with the 200-mg twice daily dose include diarrhea, thrombocytopenia, nausea, anemia and peripheral edema. The most frequent serious adverse reactions (≥ 3%) observed with the 200-mg twice daily dose were anemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia and squamous cell carcinoma of skin.

"In the U.S., there are approximately 21,000 patients with myelofibrosis, two-thirds of which have cytopenias , commonly resulting from the toxicity of other approved therapies. Severe thrombocytopenia, defined as a blood platelet count below 50 × 109/L, occurs in one-third of the overall myelofibrosis population, and has a particularly poor prognosis. With the approval of Vonjo, we are excited to now be able to offer a new therapy that is specifically approved for patients with cytopenic myelofibrosis. We are fully funded for commercial launch, following our debt and royalty transactions with DRI, and we look forward to providing Vonjo, the potential best-in-class therapy for cytopenic myelofibrosis patients, to patients within 10 days," said Adam R. Craig, MD, PhD, president and chief executive officer of CTI Biopharma.


1. CTI BioPharma announces FDA accelerated approval of VONJO™ (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. CTI BioPharma Corp. News release. February 28, 2022. Accessed February 28, 2022. https://bit.ly/3vsDPsO

2. Mesa R, Vannuchhi A, Mead A, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. The Lan. Hem. Published: March 20, 2017 DOI: https://doi.org/10.1016/S2352-3026(17)30027-3

3. Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2018;4(5):652–659. doi:10.1001/jamaoncol.2017.5818

4. Gerds A, Savona M, Scott B et al. Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Blood Adv 2020; 4 (22): 5825–5835. doi: https://doi.org/10.1182/bloodadvances.2020003314

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