FDA Approves Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes

On July 7, 2020, the Food and Drug Administration (FDA) approved Inqovi™, an oral fixed-dose combination tablet comprising 35 mg decitabine and 100 mg cedazuridine (DEC-C) for the treatment of adult patients with myelodysplastic syndromes (MDS). This approval was based on the results of Phase 3 ASTX727-02 and Phase 2 ASTX727-01-B clinical trials, which demonstrated the efficacy and safety of DEC-C in treating MDS.

Clinical Trials and Efficacy The Phase 3 ASTX727-02 trial involved a 2-sequence crossover comparing DEC-C and intravenous (IV) decitabine in adults with MDS. The study showed that the 5-day cumulative area under the curve (5-d AUC) of decitabine for DEC-C was similar to that of IV decitabine, with a geometric mean ratio of 0.99. Clinical benefit was supported by both studies, with complete remission (CR) rates of 21% and 18% in the Phase 3 and Phase 2 trials, respectively, and median duration of CR of 7.5 and 8.7 months.

Safety and Adverse Reactions Adverse reactions were consistent with those observed with IV decitabine. Common adverse reactions included neutropenia, febrile neutropenia, thrombocytopenia, and anemia. The safety profile of DEC-C tablets across all cycles was similar to that of IV decitabine, with no new adverse reactions identified.

Regulatory Insights The FDA's approval of DEC-C tablets provides an oral option for decitabine administration, which may reduce time in clinic compared to the IV formulation, a particular benefit during the COVID-19 pandemic. Patients should avoid food 2 hours before and after each DEC-C tablet dose. Post-marketing studies in patients with moderate to severe hepatic impairment and severe renal impairment were required at the time of approval, due to absence of data in these patients receiving DEC-C tablets.

Conclusion The benefit-risk analysis of the results of Study ASTX727-01-B and ASTX727-02 supported regular approval of DEC-C tablets for treatment of adult patients with MDS and CMML. Approval was based on demonstration of comparable bioavailability to IV decitabine, CR rate comparable to IV decitabine, and conversion from transfusion dependence to independence. Both common and serious toxicities were similar to IV decitabine.