A First-of-Its-Kind All-Oral Option Receives FDA Approval for Newly Diagnosed AML

Decitabine and cedazuridine tablets (Inqovi, Taiho Oncology, Inc.) with venetoclax have been approved by the FDA for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are aged 75 and older or have comorbidities that preclude the use of intensive induction chemotherapy.¹

The approval is notable for delivering the first all-oral treatment option in this setting. Until now, patients have relied on regimens built around parenteral hypomethylating agents—most commonly azacitidine plus venetoclax, the standard of care since the VIALE-A trial (NCT02993523)—requiring monthly, 7-day clinic visits for injections. The new all-oral regimen offers equivalent efficacy with significantly reduced treatment burden.²

Unpacking the New Oral Combination

Decitabine and cedazuridine is an oral tablet formulation of the hypomethylating agent (HMA) decitabine combined with cedazuridine, a cytidine deaminase inhibitor that blocks the breakdown of decitabine in the gut—allowing it to be absorbed orally with pharmacokinetic exposure equivalent to intravenous decitabine.³

Venetoclax is a selective BCL-2 inhibitor that works by blocking BCL-2, an anti-apoptotic protein that cancer cells frequently rely on to evade programmed cell death. By inhibiting BCL-2, venetoclax restores the apoptotic signaling that leukemic cells have suppressed, effectively priming them for cell death.³

The 2 agents are thought to work synergistically: decitabine, through its hypomethylating activity, reprograms the epigenetic landscape of AML cells and increases their dependence on BCL-2 for survival, while venetoclax then directly targets and disables that survival mechanism. Together, they sensitize leukemic cells and then trigger their destruction—while sparing patients the toxicity and logistical burden of intensive intravenous chemotherapy.³

Reviewing the Results

Approval was based on data from Study ASTX727-07 (NCT04657081), a single-arm, open-label phase 1/2 trial enrolling 101 adults with newly diagnosed AML who were aged 75 or older or had comorbidities precluding intensive induction chemotherapy. The primary end point was the complete remission (CR) rate.¹

Among efficacy-evaluable patients, 42 achieved a CR (41.6%; 95% CI, 31.9–51.8), with a median time to CR of 2 months (range: 0.4–15.3 months). Notably, the median duration of CR was not reached (range: 0.5–16.3 months), with 75.3% of patients maintaining remission at 12 months. Median overall survival was 15.5 months—outcomes that compare favorably with the parenteral azacitidine plus venetoclax regimen from VIALE-A, which reported a CR rate of 36.7% and median OS of 14.7 months.¹

Pharmacokinetic analyses confirmed no drug-drug interactions between oral decitabine/cedazuridine and venetoclax, supporting the safety of the combination.¹

Weighing the Safety Profile

The most common grade 3 or higher treatment-emergent adverse events were febrile neutropenia (49.5%), anemia (38.6%), and neutropenia (35.6%), consistent with the known toxicity profiles of both agents individually. The 30- and 60-day mortality rates were 3.0% and 9.9%, respectively. The prescribing information includes warnings and precautions for myelosuppression and embryo-fetal toxicity.¹

Considering the Recommended Dosage

The recommended dose is 1 tablet (35 mg decitabine and 100 mg cedazuridine) orally once daily on days 1 through 5 of each 28-day cycle, with venetoclax administered concurrently following a standard ramp-up in cycle 1. Treatment continues until disease progression or unacceptable toxicity.¹

REFERENCES

1. FDA approves oral combination of decitabine and cedazuridine tablets with venetoclax for newly diagnosed acute myeloid leukemia. FDA. May 13, 2026. Accessed May 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-oral-combination-decitabine-and-cedazuridine-tablets-venetoclax-newly-diagnosed-acute

2. Zeidan AM, Griffiths EA, Dinardo CD, et al. An all-oral regimen of decitabine-cedazuridine (DEC-C) plus venetoclax (VEN) in patients (pts) with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy: Results from a phase 2 cohort of 101 pts. J Clin Oncol. May 28, 2025. doi: 10.1200/JCO.2025.43.16_suppl.650

3. Bazinet A, Garcia-Manero G, Short N, et al. Oral decitabine and cedazuridine plus venetoclax for older or unfit patients with acute myeloid leukaemia: a phase 2 study. Lancet Haematol. July 17, 2025. doi:10.1016/S2352-3026(24)00033-4