The FDA has granted priority review to a new drug application for pacritinib as a potential treatment option for patients with myelofibrosis and severe thrombocytopenia, defined as platelet counts less than 50 x 109/L.
The FDA has granted priority review to a new drug application (NDA) for pacritinib as a potential treatment option for patients with myelofibrosis and severe thrombocytopenia, defined as platelet counts less than 50 x 109/L.1
The application was based on findings from the phase 3 PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781) trials, as well as data from the phase 2 PAC203 trial. Patients enrolled to the PERSIST-2 trial received pacritinib at a twice-daily dose of 200 mg, and 29% experienced a reduction in spleen volume of at least 30% vs 3% of those who were given best available therapy (BAT), which included ruxolitinib (Jakafi). Moreover, 23% of patients experienced a reduction in total symptom scores of at least 50% vs 13% of those given BAT.
The regulatory agency will make a decision on the NDA by November 30, 2021, under the Prescription Drug User Fee Act; it is not expected to hold an advisory committee meeting to discuss the application, according to CTI BioPharma Corp., the drug developer.
“We are pleased that the FDA’s acceptance of our NDA brings us one step closer to our goal of providing myelofibrosis patients with severe thrombocytopenia a new treatment option,” Adam R. Craig, MD, PhD, president and chief executive officer of CTI Biopharma, stated in a press release. “With commercial preparation underway, we believe we will be well positioned for a potential US launch later this year. We look forward to working with the FDA during its review of our application.”
A total of 327 patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytopenia myelofibrosis were enrolled to the PERSIST-1 trial. They were randomized 2:1 to receive pacritinib at a dose of 400 mg daily or physician’s choice of BAT, which excluded ruxolitinib.2 About 60% (55.7%) of patients in the control arm were given hydroxycarbamide, while 25.5% were treated with the watch-and-wait strategy.
The trial did not require a specific platelet count for enrollment; however, 32% of patients had levels that were under 100,000 μL, while 16% had levels under 50,000 μL. The primary end point of the phase 3 trial was spleen volume reduction of 35% or greater.
The median duration of treatment in the investigative and control arms was 16.2 months and 5.9 months, respectively. Notably, 79% of patients who originally received BAT crossed over to receive the JAK2/FLT3 inhibitor.
Data indicated that at 24 weeks of follow-up, 19.1% of patients in the pacritinib arm experienced a 35% or greater reduction in spleen volume vs 4.7% of those in the BAT arm (P = .0003).
The PERSIST-2 trial enrolled 311 patients with myelofibrosis who had platelet counts of 100,000 μL or less.3 Those in the intent-to-treat population were randomized 1:1:1 to pacritinib at a once-daily dose of 400 mg (n = 75) or a twice-daily dose of 200 mg (n = 74), or BAT (n = 72). Forty-eight percent (n = 149) of participants received prior ruxolitinib.
Regarding safety, grade 3 or 4 thrombocytopenia was experienced by 31% of patients who received the once-daily dose of pacritinib, 32% of those who received the twice-daily dose, and 18% of those who received BAT. Grade 3 or 4 anemia was reported in 27%, 22%, and 14%, of patients, respectively.
PERSIST-2 was placed on clinical hold by the FDA in February 2016, along with other efforts dedicated to evaluating the agent, following reports of patient deaths linked with intracranial hemorrhage, cardiac failure, and cardiac arrest observed on the trial. The pharmaceutical company provided the agency with final clinical study reports from both PERSIST-1 and PERSIST-2 in response to this decision; the PAC203 trial was also initiated. The following year, in January 2017, the FDA lifted the clinical hold placed on pacritinib trials.
In PAC203, investigators set out to evaluate the safety and efficacy of pacritinib in patients with primary myelofibrosis who had received prior ruxolitinib.4 Participants were given the agent at a dose of once-daily 100 mg, twice-daily 100 mg, or twice-daily 200 mg.
Results indicated that the twice-daily dose of pacritinib resulted in the most benefit in this population compared with both once-daily doses. Those with severe thrombocytopenia were observed to have spleen volume response to the agent. Pacritinib was also found to still have favorable tolerability at the higher dose, with no difference in incidence of high-grade cardiac or bleeding adverse effects vs the other doses examined.