A rolling submission of a New Drug Application has been completed for pacritinib which is seeking FDA approval as a treatment for patients with myelofibrosis who have severe thrombocytopenia.
A rolling submission of a New Drug Application has been completed for pacritinib which is seeking FDA approval as a treatment for patients with myelofibrosis (MF) who have severe thrombocytopenia defined by platelet counts less than 50 x 109/L. The submission follows a pre-NDA meeting with the FDA and the developer, CTI BioPharma Corp, during which an agreement was made on the data required to support the application, according to a press release from the company.1
The NDA for pacritinib is supported by findings from 3 clinical trials, including the phase 3 PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781) trials and the phase 2 PAC203 trial (NCT03165734).
"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 MF 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 Chief Executive Officer of CTI BioPharma.
In PERSIST-1, pacritinib was compared with the best available therapy (BAT) with primary end points of spleen volume reduction and a secondary end points of total symptom score (TSS) reduction. Significant and sustained spleen volume and symptom reduction were observed in the study, which led investigators to believe that pacritinib could be a potential treatment option for patients with MF who are cytopenic at baseline and have limited treatment options. The PERSIST-2 study was designed to confirm the results of PERSIST-1 by administering pacritinib 400 mg or 200 mg versus BAT.2
The 311 patients in PERSIST-2 with MF and thrombocytopenia had a mean age of 63.70 years. The group was 55% and 45% was female. In terms of prior treatment, 48% had prior ruxolitinib, which was also the most common form of BAT used in the study. A total of 74 patients were randomized to received pacritinib in the study and compared with 72 patients randomized to receive BAT in the intention-to-treat population. Other BATs included hydroxyurea for 19 patients, and prednisone and/or prednisolone for 13 patients. In addition, 19 patients underwent observation instead of treatment.3
With pacritinib, a spleen volume reduction of 35% or more was observed in 18% of patients. In comparison, spleen volume reductions of 35% or more were observed in only 3% of the BAT arm. The benefit observed with pacritinib in the ITT population was also observed in the study subgroups, which included patients of different gender, age, JAK2 V617F mutation status, prior treatment with JAK2 inhibitors, and baseline cytopenias.
Treatment with pacritinib also achieved a better TSS compared with BAT. At week 24, the TSS was 50% or more in 25% of the pacritinib-treated population compared with 14% of the BAT population. Receipt of ruxolitinib as BAT did improve results for patients. The study showed a median percent change in TSS at week 24 was −27% for the pacritinib 400 mg arm, −41% for the pacritinib 200 mg arm, and −15% for the BAT arm overall.
In terms of survival, there was a mild difference between the pacritinib and BAT arms which did not meet the prespecified threshold for statistical significance. The hazard ratio= for pacritinib 400 mg versus BAT was 1.18 (95% CI, 0.57- 2.44). In patients who received pacritinib 200 mg twice daily versus BAT, the HR was 0.68 (95% CI, 0.30-1.53).
The study showed nonhematological adverse events (AEs) in ≥15% of patients. The AEs observed with pacritinib were gastrointestinal AEs, fatigue, dizziness, and peripheral edema. In the BAT are, the AEs observed included abdominal pain, fatigue, diarrhea, and peripheral edema. The bulk of the AEs low grade. The most frequently seen non-hematologic AE in the pacritinib arm was diarrhea (53%). Thrombocytopenia was the most common AE that lead to treatment discontinuation in both study arms.
Study investigators determined pacritinib to be well tolerated with gastrointestinal AEs being low grade and manageable. Overall, 29 patients discontinued treatment as a result of AEs. There were also 12 deaths in the study.
"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,” said Craig, in a statement.1
1. CTI BioPharma Announces completion of rolling submission of New Drug Application (NDA) for pacritinib in myelofibrosis patients with severe thrombocytopenia. News release. CTI BioPharma, Inc. March 31, 2021. Accessed April 1, 2021. https://bit.ly/3mbncuU
2. Mesa RA Vannucchi AM, 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. Lancet Haematol. 2017;4(5):e225-e236. doi: 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