PLEASANTON, Calif.—Astex Pharmaceuticals, Inc. a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., has announced that the U.S. Food & Drug Administration (FDA) has granted orphan drug designation for the company’s fixed-dose combination of cedazuridine and decitabine (ASTX727 or C-DEC) for the treatment of myelodysplastic syndromes (MDS), including chronic myelomonocytic leukemia (CMML).
The designation follows on from the recent announcement that the Phase 3 ASCERTAIN study of ASTX727 in adults with intermediate and high-risk MDS or CMML met the primary endpoint of decitabine exposure equivalence of total 5-day dosing between oral ASTX727 and IV decitabine. The data from the study will be presented at an upcoming scientific meeting.
“We are delighted that the FDA has granted orphan drug designation for the fixed dose combination of cedazuridine with decitabine,” said Mohammad Azab, M.D., Astex Pharmaceuticals’ president and chief medical officer. “Subject to regulatory review and approvals, ASTX727 could bring a new treatment option to patients with these deadly diseases. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who contributed to the clinical development program of ASTX727.”
ASTX727 is a novel, orally administered fixed dose combination of cedazuridine, an inhibitor of cytidine deaminase, with the anti-cancer DNA hypomethylating agent, decitabine. By inhibiting cytidine deaminase in the gut and the liver, ASTX727 is designed to allow for oral delivery of the approved DNA hypomethylating agent, decitabine, at exposures which emulate exposures achieved with the approved intravenous form of decitabine administered over 5 days.
ASTX727 has been evaluated in a Phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study in patients with MDS and CMML, and a pivotal Phase 3 study (ASCERTAIN) designed to confirm the results from the Phase 1/2 study. The Phase 3 study is being extended to include patients with acute myeloid leukemia (AML) who are unsuitable candidates for intensive induction chemotherapy. The concept of using cedazuridine to block the action of cytidine deaminase is also being evaluated in a low dose formulation of cedazuridine and decitabine for the treatment of lower risk MDS.
ASTX727 is an investigational compound and is not currently approved in any country. The company plans to file an NDA with the FDA by the end of 2019.
