Phase 3 Results Support Regulatory Submission of Oral Azacitidine Plus Cedazuridine in Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

Clinical Summary:

• Design/Population: The phase 3 AZTOUND trial evaluated oral azacitidine plus cedazuridine against subcutaneous azacitidine in adult patients with myelodysplastic syndromes or chronic myelomonocytic leukemia using a randomized, open-label crossover design. 
• Key Outcomes: The trial met its primary pharmacokinetic exposure end point, which compared total cycle azacitidine exposure between oral azacitidine plus cedazuridine and subcutaneous azacitidine. Safety was consistent with the established profile of parenteral azacitidine. 
• Clinical Relevance: These findings support further regulatory development of oral azacitidine plus cedazuridine as a potential alternative to subcutaneous administration. Taiho Oncology plans to submit a New Drug Application to the FDA based on these results.

Topline results from the phase 3 AZTOUND trial demonstrated that oral azacitidine plus cedazuridine (ASTX030) met its primary pharmacokinetic exposure end point compared with subcutaneous azacitidine in patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia, supporting plans to seek US Food and Drug Administration (FDA) approval for the investigational oral regimen. 

In this open-label trial, 88 adult patients were randomized to receive either oral azacitidine plus cedazuridine or subcutaneous azacitidine. The primary end point was the ratio of total cycle azacitidine exposure, measured by the area under the concentration (AUC)-time curve from 0 to 24 hours, following administration of the oral combination compared with subcutaneous azacitidine.

According to the topline announcement, the study met its primary pharmacokinetic end point, supporting the ability of oral combination to achieve the trial’s prespecified exposure objective relative to subcutaneous treatment. Specific pharmacokinetic results, including the exposure ratio and corresponding confidence intervals, were not disclosed in the announcement.

The safety profile of oral azacitidine plus cedazuridine was reported to be consistent with that of parenteral azacitidine. Detailed adverse event rates, including grade ≥3 toxicities, serious adverse events, and treatment discontinuations were not provided. 

Azacitidine is a DNA methyltransferase inhibitor, while cedazuridine inhibits cytidine deaminase, an enzyme involved in azacitidine degradation. The combination is designed to enable oral delivery of azacitidine while maintaining systemic drug exposure.

The oral formulation may offer an alternative to injectable azacitidine for patients with MDS or chronic myelomonocytic leukemia, potentially reducing the administration burden associated with repeated clinic visits for parenteral treatment.

However, the announcement did not provide clinical efficacy outcomes, including hematologic response, transfusion independence, progression-free survival, or overall survival. The findings therefore establish that the primary pharmacokinetic objective was achieved but do not independently demonstrate equivalent clinical efficacy between the oral and subcutaneous formulations.

Taiho Oncology plans to submit a New Drug Application seeking approval of oral azacitidine plus cedazuridine for adults with MDS or chronic myelomonocytic leukemia. Detailed findings from AZTOUND are expected to be submitted for presentation at an upcoming international medical conference.

Source:

Taiho Oncology. Taiho Oncology and Taiho Pharmaceutical announce positive topline results in phase 3 AZTOUND trial evaluating oral azacitidine and cedazuridine in myelodysplastic syndromes or chronic myelomonocytic leukemia. Accessed on: October 21, 2026. https://www.businesswire.com/news/home/20260930090599/en/Taiho-Oncology-and-Taiho-Pharmaceutical-Announce-Positive-Topline-Results-in-Phase-3-AZTOUND-Trial-Evaluating-Oral-Azacitidine-and-Cedazuridine-in-Myelodysplastic-Syndromes-or-Chronic-Myelomonocytic-Leukemia