FDA Grants Pacritinib Accelerated Approval for Cytopenic Myelofibrosis With Severe Thrombocytopenia

The FDA has granted accelerated approval to pacritinib (Vonjo) for the treatment of adult patients with intermediate- or high-risk primary or secondary cytopenia myelofibrosis (MF) (post-polycythemia vera or post-essential thrombocythemia) and severe thrombocytopenia (platelet counts less than 50 x 10⁹/L).¹

Findings from the PERSIST-2 trial (NCT02055781) primarily supported today’s regulatory decision. In this study, 18% of patients with MF and severe thrombocytopenia experienced a spleen volume reduction (SVR) greater than 35% with pacritinib (either once daily at 400 mg or twice daily at 200 mg; P = .001). In comparison, only 3% of patients in the BAT group experienced a tumor reduction of 35% of more. Furthermore, 25% of the experimental cohort reported a total symptom score (TSS) of 50% or more by week 24 in the study, while 14% those who received BAT reported the same (P = .08).²

Notably, the twice-daily dose led to a significant clinical improvement in hemoglobin and transfusion burden.

"Today's approval of Vonjo establishes a new standard of care for myelofibrosis patients suffering from cytopenic myelofibrosis," John Mascarenhas, MD, principle investigator and associate professor of hematology and medical oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, stated in a press release. "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."

The PERSIST-2 trial compared pacritinib with the best available therapy (BAT) by administering the experimental agent at 400 mg once daily or 200 mg twice daily vs 200 mg BAT. A total of 311 patients participated. Prior JAK2 inhibitor therapy was permitted.

The patients were randomized 1:1 between pacritinib (n = 74) and BAT (n = 72). Forty-eight percent of participants were pretreated with ruxolitinib, which was also a common choice for BAT throughout the study and notably helped reduce TSS in patients. Hydroxyurea, prednisone, and prednisolone were also common BAT treatments.

The most common treatment-adverse events (AEs) associated with the agent include diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema. The most common serious AEs associated with the drug at a twice-daily dosage are anemia,thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia, and squamous cell carcinoma of skin.

"In the [United States], there are approximately 21,000 patients with myelofibrosis, two-thirds of which have cytopenias (thrombocytopenia or anemia), commonly resulting from the toxicity of other approved therapies,” said Adam R. Craig, MD, PhD, president and chief executive officer of CTI Biopharma. “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.”

Pacritinib is a novel oral kinase inhibitor which specifically inhibits JAK2 and IRAK1. In accordance with the accelerated approval guidelines, manufactures will need to demonstrate the agent’s clinical benefit in a confirmatory trial. The newly PACIFICA trial, which is expected to conclude in mid-2025, will seek to validate the findings demonstrated with pacritinib in PERSIST-2.

The recommended dosage for pacritinib is 200 mg orally twice daily.

References

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://prn.to/33ZY8lU
2. 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