The FDA has extended the review period for the new drug application for pacritinib as a treatment for adult patients with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis and severe thrombocytopenia with a baseline platelet count of 50 x 109/L.
The FDA has extended the review period for the new drug application (NDA) for pacritinib as a treatment for adult patients with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis and severe thrombocytopenia with a baseline platelet count of 50 x 109/L.1
The application was previously granted priority review designation, with an action date of November 30, 2021. However, the Prescription Drug User Fee Act action date has now been extended by 3 months to February 28, 2022.
In the announcement, CTI BioPharma Corp., the developer of pacritinib, noted that the FDA previously requested additional clinical data, which was submitted to the agency on November 24, 2021. The FDA recently informed CTI BioPharma that "it considers the data submission to constitute a 'major amendment' to the NDA and therefore the PDUFA date has been extended by 3 months to provide additional time for a full review of the submission."
The company stated that it is currently unaware of any major deficiencies in the application.
"CTI is continuing to engage collaboratively and constructively with the FDA during review of our NDA," Adam R. Craig, MD, PhD, president and chief executive officer of CTI Biopharma, said in a press release. "We are committed to providing patients suffering from cytopenic myelofibrosis with a new treatment option as soon as possible and are confident in pacritinib's potential to establish a new standard of care."
The NDA was based on data from the phase 3 PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781) trials, as well as findings from the phase 2 PAC203 trial. Patients enrolled to PERSIST-2 received pacritinib at a twice-daily dose of 200 mg. Of these patients, 29% experienced a reduction in spleen volume of at least 30% vs 3% of those who received best available therapy (BAT), which included ruxolitinib (Jakafi). Additionally, 23% of patients experienced a reduction in total symptom scores of at least 50% vs 13% of those who received BAT.
PERSIST-1 enrolled a total of 327 patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytopenia myelofibrosis. Participants were randomized 2:1 to receive either pacritinib at a daily dose of 400 mg or physician’s choice of BAT, which excluded ruxolitinib.2 Approximately 60% (55.7%) of patients in the control arm received hydroxycarbamide; 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, and 16% had levels under 50,000 μL. The primary end point of the trial was a spleen volume reduction of 35% or greater.
The median duration of treatment in the investigative arm was 16.2 months and 5.9 months in the control arm. Seventy-nine percent of patients who originally received BAT crossed over to receive pacritinib.
At 24 weeks of follow-up, 19.1% of patients who received pacritinib experienced a 35% or greater reduction in spleen volume vs 4.7% of those given BAT (P = .0003).
PERSIST-2 enrolled a total of 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 receive once-daily pacritinib at a dose of 400 mg (n = 75) or at a twice-daily dose of 200 mg (n = 74), or BAT (n = 72). Forty-eight percent (n = 149) of participants previously received ruxolitinib.
Regarding safety, 31% of patients who received the once-daily dose of pacritinib reported grade 3 or 4 thrombocytopenia vs 32% of those who received the twice-daily dose, and 18% of those who received BAT. Grade 3 or 4 anemia was experienced by 27%, 22%, and 14%, of patients, respectively.
The FDA placed this trial on clinical hold 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 that had been 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.
PAC203 examined the safety and efficacy of pacritinib in patients with primary myelofibrosis who had received prior ruxolitinib.4 Participants received the agent at a once-daily dose of 100 mg, a twice-daily dose of 100 mg, or twice-daily dose of 200 mg.
Results showed that the twice-daily dose of pacritinib resulted in the most benefit in this population vs both once-daily doses. Patients with severe thrombocytopenia experienced spleen volume response to the agent. Pacritinib still had favorable tolerability when given at the higher dose, with no difference in incidence of high-grade cardiac or bleeding adverse effects vs the other doses examined.