New Drug Application Planned for Submission to FDA for Pacritinib in Myelofibrosis

A New Drug Application (NDA) for pacritinib is planned to be submitted for potential accelerated approval from the FDA for the treatment of patients with myelofibrosis and severe thrombocytopenia, defined as platelet count less than 50 x 109/L, announced CTI BioPharma Corp. in a press release.

The NDA will be based on the findings from the phase 3 PERSIST-1 and PERSIST-2 clinical trial, as well as data from the phase 2 PAC203 dose-ranging study. Following agreement with the FDA, a rolling submission of the NDA is expected to commence in the next few weeks. Completion of the NDA is expected by the first quarter of 2021.

"Since the completion of the PAC203 phase 2 dose-ranging trial, we have been working collaboratively with the FDA to identify an expeditious approval pathway for pacritinib in myelofibrosis patients with severe thrombocytopenia, a patient population with an important unmet medical need due to reduced survival and limited therapeutic options. During a recent Pre-NDA meeting, we identified a data package from the PERSIST-1, PERSIST-2 and PAC203 phase 2 trials that will serve as the basis for an accelerated approval application. In particular, we discussed risk mitigation measures to address the FDA's prior concerns regarding safety," said Adam R. Craig, MD, PhD, president and chief executive officer of CTI Biopharma, in a statement.

The ongoing, randomized phase 3 PACIFICA study (NCT03165734) is expected to complete as a post-marketing commitment. This study is exploring the efficacy of pacritinib compared with the physician’s choice of therapy as treatment of patients with myelofibrosis and severe thrombocytopenia. Approximately 348 patients will be enrolled to the study and randomized to treatment 2:1.

The primary end point of PACIFICA is spleen volume, and secondary end points include total symptom score, overall survival, patient global impression of change, and safety of pacritinib compared with the physician’s choice of therapy. To be included in the study, patients must have an average platelet count of <50,000/µL at baseline, a DIPSS Intermediate-1, -2, or High-risk disease, and palpable splenomegaly ≥5 cm below the lower costal margin in the midclavicular line. Patients have to have an ECOG performance status of 0, 1, or 2 to be enrolled, as well as peripheral blast count of <10% and an absolute neutrophil count of ≥500/µL.

Patients with a life expectancy of <6 months, received prior allogeneic stem cell transplant or are eligible, have a history of splenectomy or plans to undergo 1, splenic irradiation within the last 6 months, and prior treatment with pacritinib. Patients are also ineligible if they have known human immunodeficiency virus or hepatitis A, B, or C virus.

“In myelofibrosis patients, severe thrombocytopenia occurs as a result of disease or drug-related toxicity from current therapies. There is no approved drug that specifically addresses the unmet need of the myelofibrosis patients who have severe thrombocytopenia,” stated Craig. “Pacritinib has demonstrated clinical benefit in treating these patients in multiple trials and now has the potential to become a new treatment option for treatment-naïve and second-line myelofibrosis patients in 2021.”

Pacritinib is an oral investigational kinase inhibitor that is specific for JAK2, FLT3, IRAK1, and CSF1R. These kinase mutations are associated with the development of blood-related cancers, such as myeloproliferative neoplasms. Pacritinib previously received a Fast Track designation in 2014 for the treatment of patients with intermediate- and high-risk myelofibrosis, including patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy, or patients intolerant of or whose symptoms are not well controlled on other JAK2 therapy.

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_{CTI biopharma to submit a new drug application (nda) for the accelerated approval of pacritinib for the treatment of myelofibrosis patients with severe thrombocytopenia. News Release. CTI BioPharma Corp. September 29, 2020. Accessed September 30, 2020. https://bit.ly/34jniZ4}