Helsinn and MEI Pharma announced the first patient has been dosed in the pivotal Phase 3 study of the investigational agent pracinostat in combination with azacitidine in adults with newly diagnosed acute myeloid leukemia (AML) who are unfit to receive intensive induction chemotherapy.
The randomized, double-blind, placebo-controlled study will enroll approximately 500 eligible patients worldwide. Patients will be randomized 1:1 to receive pracinostat or placebo with azacitidine as background therapy. The primary endpoint of the study is overall survival. Secondary endpoints include, among others, morphologic complete remission (CR) rate, event free survival (EFS) and duration of CR.
In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications. Under the terms of the agreement, Helsinn is granted a worldwide exclusive license to develop, manufacture and commercialize pracinostat, and is primarily responsible for funding its global development and commercialization. Pracinostat is an investigational agent and is not approved for commercial use in the U.S.
"Helsinn was delighted to be able to announce our strategic partnership with MEI Pharma last year, leveraging on the potential of pracinostat, which was demonstrated in the Phase 2 study. We are very pleased that pracinostat is moving into Phase 3, showing the continued momentum of the clinical programme,” Riccardo Braglia, Helsinn Group Vice Chairman and CEO, said. “As Helsinn broadens its focus beyond cancer supportive care and into cancer therapeutics, high quality partnerships such as our collaboration with MEI Pharma are key for Helsinn to create value and benefit more people with cancer."
The Phase 3 study of pracinostat in combination with azacitidine is open to adult patients with newly diagnosed AML who are unfit to receive standard induction chemotherapy due to age ≥ 75 years or predefined co-morbidities. Treatments will be administered based on 28-day cycles, with pracinostat or placebo administered orally once every other day, 3 times a week for 3 weeks, followed by one week of no treatment and azacitidine administered for 7 days of each cycle. Additional information regarding the study, including detailed inclusion and exclusion criteria, is available at ClinicalTrials.gov (identifier: NCT03151408).
Results from a Phase 2 open-label, single-arm, multicenter study of pracinostat and azacitidine in 50 patients aged ≥ 65 years with newly diagnosed AML not eligible for induction chemotherapy showed a median overall survival of 19.1 (95%CI: 10.0-26.5) months, one-year survival of 62% and a CR rate of 42%. Responses were durable (median CR+CRi 17.2 months). Blast clearance was rapid (median 8 weeks) while CR required prolonged therapy (>6 months) in some patients. The combination of pracinostat and azacitidine had no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included thrombocytopenia, febrile neutropenia, neutropenia, fatigue and anemia.
AML is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates about 21,380 new cases and 10,590 deaths from AML in the U.S. for 2017; the average age of a patient with AML is about 67 years. According to the Surveillance of Rare Cancers in Europe project, the incidence of AML in Europe is 3.7 per 100,000. There are currently no drugs approved in the U.S. to treat AML in patients who are unfit for intensive induction chemotherapy, though hypomethylating agents are recommended by the National Comprehensive Cancer Network (NCCN) guidelines. In the EU, azacitidine is approved for the treatment of adult patients aged 65 years or older who are not eligible for hematopoietic stem cell transplant (HSCT) with AML with >30% marrow blasts according to the World Health Organization (WHO) classification.
Pracinostat is an oral histone deacetylase (HDAC) inhibitor that is in late-stage clinical development. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy.