CTI BioPharma’s Pacritinib Meets One Co-Primary Endpoint, Just Misses Another, In PERSIST-2
Executive Summary
The US company is encouraged by top-line efficacy Phase III results showing pacritinib was effective in high-risk myelofibrosis patients with low platelet counts, and has said it is working with the FDA to lift the clinical hold imposed earlier this year because of side-effect concerns.
CTI BioPharma Corp. has been able to analyze top-line efficacy results from around a third of patients with myelofibrosis and thrombocytopenia enrolled in the PERSIST-2 Phase III study, treated before the FDA-imposed clinical hold came into effect in February, that show pacritinib met one of the co-primary endpoints of the study, and narrowly missed meeting the second.
The analysis gives some encouragement to the Seattle, Washington-based company that has been under a cloud since the FDA issued a full clinical hold on pacritinib, an investigational oral JAK2/FLT3 inhibitor, in February 2016 because of concerns about excess mortality and other adverse events, including intracranial hemorrhage, cardiac failure and cardiac arrest, in the company’s two Phase III studies, PERSIST-1 and PERSIST-2.
After the start of clinical hold, CTI BioPharma withdrew its already-filed US NDA for the product and suffered a marked decline in its share price (Also see "CTI/Baxalta Withdraw Pacritinib NDA Following More Deaths" - Scrip, 10 Feb, 2016.). In the PERSIST-2 efficacy announcement on Aug. 29, president and CEO James Bianco said he was encouraged by pacritinib’s clinical profile in this difficult-to-treat group of patients with myelofibrosis, and the company’s share price advanced from around $0.35 to $0.44 per share.
The treatment of myelofibrosis has had its fair share of investigational drug failures. One of the biggest setback in recent years was the late-stage failure of Sanofi’s Janus kinase-2 inhibitor fedtratinib in myelofibrosis in 2013 (Also see "Sanofi Oncology Strategy: A New Lease On Cancer R&D" - Scrip, 10 Aug, 2015.).
Analysts from Informa Pharma Intelligence's Biomedtracker suggest the similar mortality rates in both arms of PERSIST-2 should help CTI BioPharma in its discussions with the FDA, and they have increased the likelihood of approval rating for pacritinib by 10%, although the rating is still 20% below average for a project at this stage of development.
When CTI BioPharma’s financial results for the second quarter of 2016 were reported Aug. 4, Bianco said full analysis of the PERSIST-2 trial was key as the company continued to work with the FDA to get pacritinib off clinical hold.
The fate of pacritinib is also important for another company; Shire PLC has a licensing agreement to jointly commercialize pacritinib in the US with CTI BioPharma, and has exclusive commercialization rights for all indications outside the US (Also see "CTI Lands Baxter As Pacritinib Partner To Try To Reach Finish Line" - Pink Sheet, 15 Nov, 2013.).
Severely Ill Patients
PERSIST-2 involved patients with myelofibrosis and thrombocytopenia (less than 100,000 platelets per microliter), who are considered to have a shortened median survival time compared with myelofibrosis patients with normal platelet counts. 311 patients were enrolled and their data is available for safety assessment, and 211 patients reached week 24 of the study when efficacy was to be evaluated. Patients were treated with either pacritinib 200 mg twice-daily, 400 mg once-daily, or best supportive care including Incyte Corp./Novartis AG’s JAK1/JAK2 inhibitor Jakafi/Jakavi (ruxolitinib).
The preliminary efficacy analysis showed pacritinib therapy was associated with a statistically significant response rate in spleen volume reduction, a co-primary endpoint. The drug did not however meet the second co-primary endpoint of a greater than 50% reduction in total symptom score (TSS), although it was approaching marginal significance (p = 0.0791).
The incidence of cardiac and bleeding adverse events (all grades and grades 3-4 including deaths) and overall mortality were similar across treatment arms, CTI BioPharma said. The most common adverse events reported were diarrhea, nausea and vomiting. Additional data and analyses will be submitted for presentation at a future scientific meeting.