Taiho’s ASTX030 Meets Phase 3 Endpoint in MDS and CMML

Taiho Pharmaceutical and Taiho Oncology reported that oral azacitidine and cedazuridine (ASTX030) met the primary pharmacokinetic endpoint in the Phase 3 AZTOUND trial, demonstrating equivalent azacitidine exposure to subcutaneous azacitidine in patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). The companies plan to submit a New Drug Application (NDA) to the US Food and Drug Administration (FDA), with additional clinical findings scheduled for presentation at the 68th American Society of Hematology (ASH) Annual Meeting, December 12–15, 2026, in New Orleans.

Phase 3 Demonstrates Pharmacokinetic Equivalence

The randomized, open-label, crossover Phase 3 portion of AZTOUND evaluated azacitidine exposure following oral ASTX030 and subcutaneous azacitidine. The primary endpoint measured total-cycle azacitidine exposure over 24 hours (AUC0–24).

Among 83 patients included in the pharmacokinetic equivalence analysis, the geometric mean ratio for the primary endpoint was 95.2%, with a 90% confidence interval (CI) of 86.5–104.7%. These results met the predefined equivalence criteria, demonstrating that oral ASTX030 achieved azacitidine exposure comparable to the injectable formulation.

The oral combination also produced demethylation profiles similar to subcutaneous azacitidine, based on changes in long interspersed nuclear element-1 (LINE-1) demethylation from baseline. This provides additional pharmacodynamic evidence supporting comparable biological activity between the two administration routes.

ASTX030 uses body surface area (BSA)-based dosing to maintain appropriate azacitidine exposure. The evaluated doses were 105 mg/20 mg, 140 mg/20 mg and 175 mg/20 mg of azacitidine/cedazuridine for low-, intermediate- and high-BSA groups, respectively.

Phase 1/2 Analysis Shows Clinical Activity

Separately, pooled efficacy findings from AZTOUND Phases 1 and 2 included 45 patients with MDS treated at or near the recommended Phase 2 dose (RP2D). Evaluated dose levels included 136 mg/20 mg, 140 mg/20 mg and 144 mg/20 mg in Phase 1, and 140 mg/20 mg in Phase 2.

The median patient age was 73 years. Patients received a median of six treatment cycles, with a median treatment duration of 5.7 months and median follow-up of 25.6 months (range, 19–33).

The overall response rate (ORR) was 44.4% (95% CI, 29.6–60.0%), including complete responses in nine patients (20%). ORR included complete response, partial response, marrow complete response and hematologic improvement, according to International Working Group 2006 criteria.

Median overall survival was not reached, with a 95% CI of 21.6 months to not evaluable. These findings provide an early indication of clinical activity, although the pooled Phase 1/2 analysis remains separate from the Phase 3 pharmacokinetic assessment.

Safety Profile Consistent with Azacitidine

In the Phase 3 safety population (n=71), median treatment duration was 1.6 months. Treatment-emergent adverse events (TEAEs) occurred in 92% of patients, with 68% experiencing Grade 3 or higher events.

The most common Grade 3 or higher events were anemia (24%) and neutropenia (20%). Serious adverse events occurred in 34% of patients, most frequently febrile neutropenia (9%) and pneumonia (6%). Investigators identified no new safety signals, and the overall profile remained consistent with the established safety characteristics of parenteral azacitidine.

 FDA Submission Planned as Development Advances

Taiho Oncology intends to submit an NDA to the FDA based on the AZTOUND results. Chief Medical Officer Harold Keer, MD, PhD, said the upcoming ASH presentation will provide further pharmacokinetic findings as the company advances ASTX030 toward regulatory review.

The Phase 3 study enrolled 88 adults with MDS or CMML. Although the pharmacokinetic and safety analyses have reported findings, other objectives, including clinical activity, remain under evaluation.

ASTX030 combines azacitidine, a DNA methyltransferase inhibitor, with cedazuridine, a cytidine deaminase inhibitor that prevents enzymatic degradation of azacitidine and supports its oral administration.

The key development milestone is the demonstration of pharmacokinetic equivalence, rather than established Phase 3 efficacy. If approved, ASTX030 could provide an oral alternative to injectable azacitidine for eligible patients with MDS or CMML, potentially reducing treatment-related logistical burdens. However, its clinical benefit and regulatory approval will depend on the complete clinical evidence and FDA review. The combination remains investigational and is not approved by any health authority.

Reference

 Taiho Pharmaceutical and Taiho Oncology to Present Data from AZTOUND Trial Evaluating Oral Azacitidine and Cedazuridine in Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia at the 68^th ASH Annual Meeting and Exposition, Taiho Pharma, 05 November 2026

A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination with Venetoclax in AML (AZTOUND Study), ClinicalTrials.gov ID NCT04256317