CTI BioPharma To Submit NDA For Pacritinib In Q4 Based Primarily On Data From Single Pivotal Persist-1 Trial

On September 23, 2015 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported its plan to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) following a productive pre-NDA meeting for pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R (Press release, CTI BioPharma, SEP 23, 2015, View Source [SID:1234507526]).

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The company expects to submit the NDA in the fourth quarter of 2015 and to request accelerated approval for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/uL). The NDA will be based primarily on data from the PERSIST-1 Phase 3 trial – as well as data from Phase 1 and 2 studies of pacritinib – and additional information requested by the FDA, including a separate study report and datasets for the specific patient population with low platelet counts of less than 50,000 per microliter (<50,000/uL) for whom there are no approved drugs. Submission of an NDA after a single Phase 3 trial under accelerated approval, instead of waiting to complete two Phase 3 trials, could potentially reduce time to market by up to 14 months.

Myelofibrosis is a rare and serious chronic blood cancer that can affect patients of all ages with a median age of 65 years, with an estimated prevalence in the United States of approximately 18,000 patients.

"This improved timing on the plan to submit an NDA – which is supported by data after completion of the PERSIST-1 trial – will allow us the potential for making pacritinib available to patients with low platelet counts earlier than expected," said James A. Bianco, M.D., President and CEO of CTI BioPharma. "We look forward to working with the FDA on the submission and review of this application."

PERSIST Update

Pacritinib is currently being evaluated in two Phase 3 clinical trials, known as the PERSIST program, for patients with myelofibrosis. PERSIST-1 is a randomized, open-label, multicenter Phase 3 trial comparing the efficacy and safety of pacritinib with that of best available therapy (exclusive of a JAK inhibitor) in 327 enrolled patients with myelofibrosis (primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis), regardless of the patients’ platelet counts. PERSIST-2 is a randomized, open-label, multicenter Phase 3 clinical trial evaluating pacritinib compared to best available therapy (BAT), including the approved JAK1/JAK2 inhibitor dosed according to product label for patients with myelofibrosis whose platelet counts are less than or equal to 100,000 per microliter. In October 2013, CTI BioPharma reached agreement with the FDA on a Special Protocol Assessment (SPA) for the PERSIST-2 trial. The SPA is a written agreement between CTI BioPharma and the FDA regarding the design, endpoints and planned statistical analysis approach of the trial to be used in support of a potential NDA submission. The design of PERSIST-1 and PERSIST-2 allows for patients on the BAT arm to crossover and receive treatment with pacritinib if their disease progresses or after they achieve the 24-week measurement endpoint. Although crossover design of clinical trials may confound evaluation of survival, such designs are frequently used in cancer studies, and the FDA has approved multiple oncology drugs that utilized crossover design in Phase 3 trials. The Independent Data Monitoring Committee (IDMC) for the PERSIST program recommended patients on the best available therapy arm should not crossover to receive pacritinib due to non-statistically significant safety concerns in patients who crossover after 24 weeks, which crossover confounds evaluation of survival. After receiving input from external independent experts and providing the FDA the PERSIST-1 data, IDMC’s recommendation and correspondence, CTI BioPharma and Baxalta notified the FDA of the decision to proceed per protocol. Following a written response in lieu of a Type C meeting with the FDA, CTI BioPharma and Baxalta determined that no modifications to the ongoing trials were required. Enrollment in PERSIST-2, which is designed to enroll up to 300 patients in North America, Europe, Australia, New Zealand and Russia is continuing. Based on current timelines, PERSIST-2 enrollment is expected to be completed in the first quarter of 2016. Additional details on PERSIST-2 are available at www.clinicaltrials.gov or www.PERSISTprogram.com.

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy, or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy. The FDA’s Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Pacritinib does not have regulatory approval and is not commercially available.

CTI BioPharma and Baxalta (NYSE:BXLT) are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.