Cedazuridine + decitabine

Unassigned

New Medicines

Intermediate and high-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) and acute myeloid leukaemia (AML)

Information

New formulation
Astex Pharmaceuticals
Astex Pharmaceuticals

Development and Regulatory status

None
Phase III Clinical Trials
Pre-registration (Filed)
Yes
Feb 20 · FDA grant priority review for oral C-DEC (cedazuridine and decitabine) as a treatment for adults with previously untreated intermediate- and high-risk MDS including CMML. The company’s New Drug Application was accepted based on data from the PIII ASCERTAIN study.[3,4]
Aug 19 · FDA granted orphan drug designation to oral fiexed dose combination of cedazuridine/ decitabine for treatment of myelodysplastic syndromes.[4]

Category

Fixed-dose combination of decitabine (anticancer DNA hypomethylating agent) and cedazuridine (a DNA cytidine deaminase inhibitor which enables oral delivery of decitabine). [2,3]
The incidence of MDS is ~ 4/100,000 population/year with an increasing overall prevalence due to an ageing population [1]. CMML and AML are rare. Around 3,100 people are diagnosed with AML in the UK every year. [2]
Intermediate and high-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) and acute myeloid leukaemia (AML)
Oral

Trial or other data

Feb 20 · PIII ASCERTAIN crossover, open, prospective, randomised, sequential trial (NCT03306264) evaluated the 5-day decitabine exposure equivalence of oral C-DEC and IV decitabine (100mg cedazuridine/35mg decitabine) at centres in the US and Canada. It is enrolling ~200 pts. It showed that the fixed dose oral combination emulates the pharmacokinetic (PK) & pharmacodynamic (PD) characteristics of a 1-hour i.v. infusion of decitabine in pts with intermediate and high-risk MDS and CMML. The study has been expanded to include enrollment of AML pts in the EU. Safety was consistent with i.v. decitabine and common adverse events were thrombocytopenia, neutropenia, anaemia and fatigue. [3-5]