The FDA has requested more time to review data from 3 pivotal trials featuring pacritinib for the treatment of intermediate or high-risk primary or secondary myelofibrosis with severe thrombocytopenia, thus extending the review period for the agent’s new drug application.
The FDA has extended the review period for pacritinib’s (Temetko) new drug application for the treatment of patients with intermediate or high-risk primary or secondary myelofibrosis with thrombocytopenia, with a baseline platelet count of less than 50 x 109/L, according to a press release from the drugs developer, CTI BioPharma Corp.1
An original prescription drug user fee act (PDUFA) date was scheduled for November 30, 2021, however, following a request for more data that was submitted on November 24, 2021, the FDA extended the PDUFA date to February 28, 2022. The FDA had previously granted pacritinib priority review based on the results of the phase 3 PERSIST-2 (NCT02055781) and PERSIST-1 (NCT01773187) trials, as well as the phase 2 PAC203 clinical trial (NCT03165734).
“CTI is continuing to engage collaboratively and constructively with the FDA during review of our [new drug application]. 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,” Adam R. Craig, MD, PhD, president and chief executive officer of CTI Biopharma, said in the press release.
The phase 3 PERSIST-2 study, which assessed the use of pacritinib compared with best available therapy in patients with myelofibrosis and thrombocytopenia, enrolled 311 patients.2 Those who enrolled were randomized into 1 of 3 treatment regimens, including pacritinib once daily (n = 104), pacritinib twice daily (n = 107), or a best alternative treatment (n = 100). Best alternative treatments included ruxolitinib (Jakafi; 45%), hydroxyurea (19%), and prednisone and/or prednisolone (13%).
At the 24-week mark, 15% of patients taking pacritinib once daily and 22% taking the agent twice daily experienced had a 35% or higher reduction in spleen volume compared with 3% of those receiving a best alternative treatment. Differences between the 3 treatment groups did not reach significance in terms of overall survival, including between the once daily (HR, 1.18; 95% CI, 0.57-2.44) and twice daily pacritinib arms (HR, 0.68; 95% CI, 0.30-1.53). The treatment also yielded a 25% reduction in total symptom score of 50% or more in the pacritinib arms vs 14% in the control group.
Additionally, the phase 3 PERSIST-1 study examined the use of pacritinib vs best available therapy for myelofibrosis regardless of baseline cytopenias. Results from the trial indicated that pacritinib was well tolerated and resulted in sustained spleen volume and symptom reduction.3 This study showed that patients with baseline cytopenias could have a treatment option with pacritinib. At week 34, 19% (n = 42) of patients treated with pacritinib experienced a 35% or more reduction in spleen volume compared with 5% (n = 5) in the best alternative treatment group (P = .0003).
The most common grade 3/4 adverse effects through week 24 in the pacritinib group were anemia (17%), thrombocytopenia (12%), and diarrhea (5%) compared with anemia (15%), thrombocytopenia (11%), dyspnea (3%), and hypotension (3%) in the best available therapy cohort. A total of 12% (n = 27) of patients died in the pacritinib group compared with 13% (n = 14) in the best alternative treatment group.
Pacritinib was also assessed as part of the dose-finding phase 2 PAC203 study vs ruxolitinib in patients with myelofibrosis and severe thrombocytopenia.4 Patients who were administered 200 mg of pacritinib twice daily experienced the highest reduction in spleen volume and total symptom score. In particular, patients with a baseline platelet count of less than 50 x 103/mL experienced a promising reduction in splenic volume (14%).
Patients who were treated with 200 mg of pacritinib twice a day did not experience an excess of grade 3 or higher hemorrhagic or cardiac events.
1. CTI BioPharma announces extension of FDA review period for pacritinib in myelofibrosis with severe thrombocytopenia. News Release. CTI BioPharma Corp. November 30, 2021. Accessed December 1, 2021. https://prn.to/3IaTRLx
2. Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis. JAMA Oncol. 2018;4(5):652-659. doi:10.1001/jamaoncol.2017.5818
3. 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
4. Gerds AT, Savona MR, Scott BL, 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:10.1182/bloodadvances.2020003314