EMA Accepts Marketing Authorization Application for Decitabine and Cedazuridine in Adult AML

A marketing authorization application for decitabine and cedazuridine (Inqovi; ASTX727) was accepted by the European Medicines Agency for the treatment of adult patients with acute myeloid leukemia (AML) who are not eligible for treatment with standard induction chemotherapy, according to a press release from Astex Pharmaceuticals.¹

The application is supported by findings from the phase 3 ASCERTAIN trial (NCT03306264), assessing the pharmacokinetics of oral fixed dose decitabine and cedazuridine compared with intravenous decitabine alone.² The study met its primary end point, with the oral combination achieving exposure equivalence compared with the standard regimen of intravenous decitabine for 5 days. Safety findings of decitabine and cedazuridine remained consistent with those expected for intravenous decitabine.

Moreover, among all treated patients (n = 87), the complete response rate was 21.8% (95% CI, 13.7%-32.0%). Additionally, after a median follow-up of 7.95 months, the median overall survival was 7.9 months (95% CI, 5.9-13.0), with 54.0% of patients reaching the death event at the data cutoff. Patients will continue to be followed.

The FDA approved the oral combination of decitabine and cedazuridine for patients with myelodysplastic syndromes(MDS) in July 2020.³ The decision was based on findings from 2 randomized, crossover trials: the ASTX727-01-B trial (NCT02103478) and the ASTX727-02 (NCT03306264) trial, assessing oral decitabine in patients with MDS chronic myelomonocytic leukemia, and AML, respectively.

References

1. European Medicines Agency commences review of oral fixed-dose combination of decitabine and cedazuridine for the treatment of adults with acute myeloid leukemia. News release. Astex Pharmaceuticals. August 22, 2022. Accessed August 23, 2022. https://yhoo.it/3R1c5TB
2. Geissler K, Koristek Z, Bernal del Castillo T, et al. Pharmacokinetic exposure equivalence and preliminary efficacy and safety from a randomized cross over phase 3 study of an oral hypomethylating agent, ASTX727 (DEC-C) compared to IV decitabine in AML patients. HemaSphere. 2022;6(S3):910-911.
3. FDA approves oral combination of decitabine and cedazuridine for myelodysplastic syndromes. News release. FDA. July 7, 2020. Accessed August 23, 2022. https://bit.ly/3pHeQhk