FDA Reviews Decitabine, Cedazuridine, and Venetoclax for AML Patients

The U.S. Food and Drug Administration (FDA) is currently reviewing a supplemental new drug application (sNDA) for a combination therapy involving decitabine, cedazuridine (Inqovi), and venetoclax (Venclexta) aimed at treating adult patients diagnosed with acute myeloid leukemia (AML) who are not eligible for intensive induction chemotherapy. This review follows promising results from the phase 2b ASCERTAIN-V trial (NCT04657081), which demonstrated a complete response rate of 46.5% among participants, as reported at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) Congress.

The ASCERTAIN-V trial evaluated this all-oral regimen in 101 adult patients, with a median age of 78 years, who were deemed ineligible for intensive chemotherapy. The trial recorded significant efficacy outcomes, including a complete response (CR) rate of 46.5% (95% CI, 36.5%-56.7%) and a combined CR rate of 63.4% (95% CI, 53.2%-72.7%) when factoring in incomplete hematologic recovery. Notably, the study found that 75.3% of those who achieved a complete response maintained their status at 12 months, with an estimated median overall survival of 15.5 months (95% CI, 7.6-NE).

According to Dr. Harold Keer, Chief Medical Officer of Taiho Oncology, "The FDA's acceptance of our sNDA signifies the urgent need for innovative cancer treatments for this patient population. If approved, this combination therapy could represent the first all-oral treatment option for AML patients not suitable for intensive chemotherapy."

The regimen involves administering decitabine and cedazuridine on days 1 to 5 of each 28-day cycle. For the initial cycle, venetoclax is introduced with a ramp-up dosing schedule. The safety profile of the combination has been promising, with no new safety concerns reported. Adverse events were recorded in 99% of participants, with febrile neutropenia, anemia, and neutropenia being the most common grade 3 or higher adverse effects.

The FDA had previously approved decitabine and cedazuridine in July 2020 for specific subtypes of myelodysplastic syndromes, underscoring the clinical relevance of this combination therapy in oncology. As the FDA's decision is anticipated, the clinical community remains hopeful for a breakthrough that could enhance the treatment landscape for AML patients who face significant barriers to current therapies.

In conclusion, the potential approval of this all-oral regimen marks a significant advancement in the management of newly diagnosed AML, potentially providing a much-needed option for patients who are unable to tolerate traditional intensive chemotherapy. As the FDA deliberates, the implications of this therapy could extend far beyond individual patient outcomes, potentially influencing treatment protocols and improving survival rates in this vulnerable population.