The FDA has extended the review period of the new drug application for pacritinib as treatment of patients with myelofibrosis and severe thrombocytopenia.
The FDA has extended the review period of the new drug application (NDA) for pacritinib as treatment of patients with myelofibrosis and severe thrombocytopenia, defined as a platelet count less than 50x109/L. The new target action date is a February 28, 2022, according to a press release issued by CTI BioPharma Corp.1
"CTI is continuing to engage collaboratively and constructively with the FDA during review of our NDA," said Adam R. Craig, MD, PhD, president and chief executive officer of CTI Biopharma, 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."
Pacritinib is an oral macrocyclic Janus kinase inhibitor specifically used to inhibit JAK2, IRAK1, and CSFIR. The JAK family of enzymes promotes normal blood cell growth in patients because JAK is central component in signal transaction pathways. A direct relationship between mutations in these pathways and the development of hematological cancers like myeloproliferative neoplasms, leukemia, and lymphoma has been found by clinicians. Moreover, due to pacritinib’s inhibition of c-fms, IRAK1, JAK2, and FLT3, the agent may be useful for the treatment of acute myeloid leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and chronic lymphocytic leukemia.
The NDA was based upon results from the phase 3 PERSIST-1 (NCT01773187), the phase 3 PERSIST-2 (NCT02055781), and phase 3 PAC203 trials (NCT03165734).
PERSIST-1 looked at 327 patients with myelofibrosis who either received pacritinib or the best available therapy.2 By week 24 of the study, researchers found that 19% of patients in the pacritinib arm achieved the primary endpoint of spleen reduction size by 35% or more, compared to 5% in the control group. Moreover, 90 patients in the control group were switched to pacritinib at a median of 6.3 months on the trial.
PERSIST-1 led to PERSIST-2 which enrolled 311 participants with myelofibrosis who also had thrombocytopenia, and the primary endpoint of the study was to compare efficacy of pacritinib to the best available therapy.3 Patients were divided into 3 arms; in arm 1, patients received pacritinib once daily; in arm 2, patients received pacritinib twice daily; and in arm 3, patients received the best available therapy.
Twice a day pacritinib was associated with better outcomes compared to patients on the best available therapy. Eighteen percent of patients in the twice-daily pacritinib arm had a spleen reduction of 35% or greater compared to 3% of patients on the best available therapy.
In the PAC203 trial an estimated 348 patients have been enrolled and were randomized to receive 200 mg of the approved agent compared to the physician’s choice of therapy.4 Fifty-four patients received 200 mg of pacritinib twice daily and 5 saw a reduction of spleen size. Fifty-five patients who received 100 mg twice per day and 1 patient saw a reduction in spleen size compared to those who received the same amount once daily none saw a reduction in spleen size.
1. CTI BioPharma announces extension of fda review period for pacritinib in myelofibrosis with severe thrombocytopenia. News release. CTI BioPharma. November 30, 2021. Accessed November 30, 2021. https://bit.ly/3oaXfOw
2. Mesa R, Vannuchhi A, 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. The Lan. Hem. Published: March 20, 2017. doi : https://doi.org/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
4. Gerds A, Savona M, Scott B 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: https://doi.org/10.1182/bloodadvances.2020003314