FDA Accepts NDA For Pacritinib to Treat Myelofibrosis and Thrombocytopenia


The FDA has accepted and granted priority review to a new drug application for pacritinib for the treatment of patients with myelofibrosis and severe thrombocytopenia, defined as a platelet count less than 50x109/L.

The FDA has accepted and granted priority review to a new drug application (NDA) for pacritinib for the treatment of patients with myelofibrosis and severe thrombocytopenia, defined as a platelet count less than 50x109/L, according to a press release by CTI BioPharma Corp.1

Pacritinib is an oral kinase inhibitor with specificity for JAK2, IRAK1, and CSFIR. Normal blood cell growth is promoted by the JAK family of enzymes due to it being a central component in signal transaction pathways. A direct relationship has been found between mutations in these pathways and the development of blood-related cancers such as myeloproliferative neoplasms, leukemia, and lymphoma. Additionally, due to the agent’s inhibition of c-fms, IRAK1, JAK2, and FLT3, pacritinib may be useful for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and chronic lymphocytic leukemia (CLL).1

The NDA was based on results of the phase 3 PERSIST-1 (NCT01773187), the phase 3 PERSIST-2 (NCT02055781), and phase 2 PAC203 trials (NCT03165734).

During PERSIST-1, which included enrollment of 327 participants with myelofibrosis, patients either received pacritinib or the best available therapy. The primary outcome of the study was spleen volume reduction and the secondary outcome was total symptom score reduction. 

The study found that by week 24, the primary end point of spleen size reduction by 35% or more was achieved in 19% of patients in the pacritinib group versus 5% in the control group. Additionally, 90 patients in the control group switched to pacritinib at a median of 6.3 months.2

PERSIST-2 enrolled 311 participants with myelofibrosis with thrombocytopenia. The primary end point of the study was to compare the efficacy of pacritinib to the best available therapy. Secondary outcomes included efficacy of a once daily dose of the agent versus the best available therapy or the efficacy of a twice-daily dose of pacritinib versus the best available therapy.

The study was composed of 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. 

According to results, twice a day pacritinib was associated with better outcomes compared with best-available therapy. Of the patients assigned to twice daily pacritinib, 18% saw a spleen reduction of 35% or greater compared to 3% of those who received best available therapy.3

During the PAC203 trial, which has an estimated enrollment of 348 participants, patients were randomized to receive either 200 mg of pacritinib twice a day, with or without food, or physician’s choice of therapy. The primary outcome of the study is spleen volume. Secondary outcomes include total symptom score, overall survival, and safety. Other outcomes measured were best response in spleen reduction, red blood cell count, hemoglobin levels, and platelet count. 

According to results, of the 54 patients who received 200 mg of the agent twice per day, 5 saw a reduction in spleen size. Of the 55 who received 100 mg twice per day, 1 saw a reduction in spleen size. Of the 52 patients who received 100 mg of the drug once a day, none saw a reduction in spleen size.4

"The completion of the pacritinib NDA submission is the result of many years of clinical research and a collaborative and constructive dialogue with the FDA on how pacritinib could address the unmet medical need of myelofibrosis patients with severe thrombocytopenia. MF patients with severe thrombocytopenia experience poor treatment outcomes, primarily due to their severely cytopenic disease and the significant limitations of approved therapies," said Adam R. Craig, MD, PhD, president and CEO of CTI BioPharma, in a press release. "CTI has initiated pre-commercialization activities and has completed the hiring of a commercial leadership team. Assuming a successful priority review of the NDA, we are preparing for a commercial launch of pacritinib before the end of 2021. We look forward to providing updates on the NDA and our commercialization plans over the coming months."

1.CTI BioPharma announces acceptance of NDA granted with priority review of pacritinib for treatment of patients with myelofibrosis. News release. CTI Biopharma. https://bit.ly/3uDXWQx.
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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