PRINCETON, N.J. — Taiho Oncology, Inc. announces publication of the final results from the pivotal ASCERTAIN clinical trial of fixed-dose oral decitabine and cedazuridine (INQOVI®) compared to intravenous decitabine in adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML).
The ASCERTAIN trial was the first Phase 3 trial to demonstrate pharmacologic equivalence between an oral and an intravenous (IV) formulation of a hypomethylating agent for use in the treatment of patients with MDS or CMML. As reported in the January 2 issue of The Lancet Haematology, median overall survival (mOS) in the trial population was approximately 32 months. In addition, the overall response rate was 62% in the intent to treat patient population. The percentage of patients in this trial who moved to transplantation reached 20%, exceeding expected transplantation rates in patients receiving hypomethylating agents for MDS and CMML.
Safety findings from the study were comparable with those previously observed with IV decitabine. The most common treatment-emergent adverse events of thrombocytopenia, neutropenia and anemia were consistent with expected adverse events with parenteral hypomethylating agent treatment.
The data from the study supported the simultaneous approval of INQOVI® by the U.S. Food and Drug Administration and Health Canada in July 2020 for the treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
“Until recently, azacitidine and decitabine, both widely used hypomethylating agents, were available only in parenteral form, requiring patients with MDS and CMML to travel to treatment centers daily for 5 or 7 consecutive days of each 28-day treatment cycle,” said Guillermo Garcia-Manero, MD, Professor, Department of Leukemia, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, Houston, and the lead author on the publication. “The ASCERTAIN study has demonstrated that the orally delivered fixed dose combination of decitabine and cedazuridine is an alternative option to parenteral administration of decitabine for patients with these diseases. The observed median overall survival of greater than 30 months in the ASCERTAIN study compared with historical controls is encouraging.”
Added Tehseen Salimi, MD, MHA, Senior Vice President and Head of Medical Affairs, Taiho Oncology, Inc., “Patients living with MDS and CMML can benefit from the convenience of an at-home hypomethylating agent treatment that may potentially reduce the number of office visits and the travel that comes with it.”
About the ASCERTAIN Trial
The Phase 3 ASCERTAIN clinical trial was a multicenter, randomized, open-label, crossover pharmacokinetics (PK) study comparing oral decitabine (35mg) and cedazuridine (100mg) fixed-dose combination tablet given once daily for 5 days on a 28-day cycle to IV decitabine (20mg/m2) administered as a daily 1-hour IV infusion for 5 days on a 28-day cycle, in the first 2 cycles in patients with MDS and CMML. Patients continued to receive oral decitabine and cedazuridine from Cycle 3 onwards. The primary endpoint of the study was total 5-day area-under-the-curve (AUC) equivalence of oral decitabine and cedazuridine and IV decitabine.
About Decitabine and Cedazuridine Fixed-Dose Combination
This product is an orally administered, fixed dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine, an inhibitor of cytidine deaminase. By inhibiting cytidine deaminase in the gut and the liver, the fixed dose combination is designed to allow for oral delivery of decitabine over five days in a given cycle to achieve comparable systemic exposure to IV decitabine administered over five days.
The oral decitabine and cedazuridine fixed-dose combination has been evaluated in a Phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study, and a Phase 3 exposure equivalence study in patients with MDS and CMML – the ASCERTAIN study.
About Taiho Oncology, Inc.
The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small molecule clinical candidates targeting solid tumor and hematological malignancies, with additional clinical candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company’s European and Canadian operations, which are located in Zug, Switzerland and Oakville, Ontario, Canada.
Contact
Judy Kay Moore
(574)526-2369