On June 5, 2017 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported findings from a genetic mutation analysis of patients in a Phase II clinical study of the investigational drug pracinostat and azacitidine in acute myeloid leukemia (AML), including a significant correlation between genetic mutations in the DNA methylation pathway and clinical response (Press release, MEI Pharma, JUN 5, 2017, View Source [SID1234519401]). These data are being presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago. Schedule your 30 min Free 1stOncology Demo! Available samples from 41 of the 50 patients enrolled in the Phase II study were sequenced to characterize the genetic mutation profile of these patients. The overall mutation profile of the patients in this study appear to be generally typical of an older population with AML1 and are also common in myelodysplastic syndrome (MDS)2. The most frequent mutations, occurring in 37% of samples studied (15 41), were found in the DNA methylation pathway, including DNMT3A, IDH1, IDH2 and TET2. Patients with these mutations had a complete response (CR) rate of 60%, a significant improvement (p=0.027) over patients with the wild-type genes (22%).
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Notably, the phase II analysis also showed that median overall survival was roughly equivalent in patients with mutations typically associated with de novo AML (18.1 months) and secondary AML (17.7 months). In a recent study, the standard-of-care regimen of cytarabine and daunorubicin (7+3) in patients with secondary AML showed a median overall survival of 5.95 months3.
"This mutational analysis enabled us to identify frequently occurring genetic abnormalities that may predict outcomes in older AML patients treated with the combination of pracinostat and azacitidine," said Dr. Guillermo Garcia-Manero, MD Anderson Cancer Center, principal investigator of the study. "In addition, we confirmed that the mutation profile in the Phase II AML study was representative not only of the larger population of older AML patients, but common in MDS patients as well. Finally, longitudinal sequencing analyses showed that continued treatment with pracinostat and azacitidine increases the rate of minimal residual disease clearance. These findings combine to support the upcoming Phase III study of pracinostat plus azacitidine in AML as well as the Phase II dose-optimization study of pracinostat and azacitidine in high and very high MDS."
A copy of the poster, entitled "Correlation Between Mutation Clearance and Clinical Response in Elderly Patients with Acute Myeloid Leukemia (AML) Treated with Azacitidine and Pracinostat," is now available at www.meipharma.com. These data will also be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Madrid on Friday, June 23, 2017.
Results from the Phase II study of pracinostat and azacitidine in elderly patients with AML 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%. CR rate and overall survival were consistent across patient subsets. Responses were durable (median CR+CRi 17.2 months), blast clearance was rapid (median 8 weeks) and maximum clinical benefit 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. These results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2016.
About Pracinostat
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. In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications. Site recruitment is ongoing for a global Phase III study of pracinostat and azacitidine in newly diagnosed AML patients who are ≥75 years of age or unfit for intensive induction chemotherapy. A Phase II dose-optimization study of pracinostat and azacitidine in patients with high and very high risk MDS is expected to initiate this month. Pracinostat is an investigational agent and is not approved for commercial use in the U.S.