Rolling Submission Completed for Pacritinib for Myelofibrosis With Severe Thrombocytopenia

The rolling submission of a new drug application has been completed and submitted to the FDA to support the approval of pacritinib as a treatment for patients with myelofibrosis and severe thrombocytopenia defined as having platelet counts less than 50 x 109/L.

The rolling submission of a new drug application has (NDA) been completed and submitted to the FDA to support the approval of pacritinib as a treatment for patients with myelofibrosis and severe thrombocytopenia defined as having platelet counts less than 50 x 109/L.1

The application is based on available data from the phase 3 PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781) trials, as well as findings from the phase 2 PAC203 trial.

“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 [patients with] myelofibrosis with severe thrombocytopenia,” Adam R. Craig, MD, PhD, president and chief executive officer of CTI BioPharma, stated in a press release.

As part of the PERSIST-1 trial, a total of 327 patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytopenia myelofibrosis were randomized 2:1 to the JAK2/FLT3 inhibitor delivered at a daily dose of 400 mg or physician’s choice of best available therapy excluding ruxolitinib (Jakafi).2 The most frequently utilized treatments in the control arm were either hydroxycarbamide, which was used in 55.7% of patients, or a watch-and-wait strategy, which was used for 25.5% of patients.

Notably, no specific platelet level was required for enrollment, but 32% of participants had levels that fell under 100,000 μL and 16% had levels under 50,000 μL. The primary objective of the trial was spleen volume reduction of 35% or greater.

In the investigative arm, the median duration of treatment was 16.2 months vs 5.9 months in the control arm. Seventy-nine percent of patients who received best available therapy crossed over to receive pacritinib.

After 24 weeks of follow-up, data indicated that a 35% or greater reduction in spleen volume was noted in 19.1% of those in the investigative arm vs just 4.7% of those in the control arm (P = .0003).

The PERSIST-2 trial enrolled a total of 311 patients with myelofibrosis who had platelet counts of 100,000 μL or less.3 Participants who comprised the intent-to-treat efficacy population were randomized in a 1:1:1 fashion to receive pacritinib at either a once-daily dose of 400 mg (n = 75) or a twice-daily dose of 200 mg (n = 74), or best available therapy (n = 72). Notably, 48% (n = 149) of patients had previously received ruxolitinib.

Results demonstrated that more patients in the investigative arm experienced a 35% or greater reduction in spleen volume than those in the control arm, at 18% vs 3%, respectively (P = .001). Moreover, the JAK2/FLT3 inhibitor reduced total symptom score by 50% or more vs best available therapy, at 25% vs 14%, respectively (P = .08); however, this reduction was not determined to be of statistical significance.

When pacritinib was given at a twice-daily dose, the agent resulted in substantial improvements in greater spleen volume reduction compared with best available therapy, at 22% vs 3%, respectively (P = .01). At this dose level, improvements in hemoglobin and reduced transfusion burden were observed to be most significant.

The most frequently experienced grade 3 or 4 adverse effects with pacritinib and best available therapy included thrombocytopenia (31% at once-daily dose; 32% at twice-daily dose; 18% with best available therapy) and anemia (27%, 22%, and 14%, respectively).

PERSIST-2 was previously placed on a clinical hold by the FDA in February 2016, as were other research efforts examining pacritinib. The decision followed reports of patient deaths linked with intracranial hemorrhage, cardiac failure, and cardiac arrest that had been observed in this trial. In response, CTI BioPharma provided the regulatory agency with final clinical study reports from PERSIST-1 and PERSIST-2 and also initiated the PAC203 trial. In January 2017, the FDA lifted the clinical hold on pacritinib trials.

The goal of the PAC203 trial was to further examine the safety and efficacy of pacritinib in patients with primary myelofibrosis who previously received ruxolitinib.4 Here, patients were administered pacritinib at 1 of 3 doses: 100 mg once daily, 100 mg twice daily, or 200 mg twice daily.

Data demonstrated that the twice daily dose of the agent led to the strongest benefit in this population compared with the once daily doses. Patients who had severe thrombocytopenia, defined as having platelet counts under 50,000 μL, experienced spleen volume responses with treatment. The agent demonstrated favorable tolerability at the higher dose, with no difference in incidence of high-grade cardiac or bleeding toxicities reported compared with the other doses.

“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,” added Craig in the release. “We look forward to providing updates on the NDA and our commercialization plans over the coming months.”


  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 Corp. March 31, 2021. Accessed March 31, 2021.
  2. Results of the PERSIST-1 phase III study of pacritinib (PAC) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia-myelofibrosis (PET-MF). J Clin Oncol. 2015;(suppl 33):LBA7006.
  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 AT, Savona MR, Scott BL, et al. Results of PAC203: a randomized phase 2 dose-finding study and determination of the recommended dose of pacritinib in patients with myelofibrosis. Accessed March 31, 2021.