FDA gives the nod for Taiho’s Inqovi with venetoclax in newly diagnosed acute myeloid leukemia

Edited by Robert McTiernan··2 min read

An oral alternative to intravenous hypomethylating therapy will be made available for acute myeloid leukemia (AML) patients after the US FDA’s approval of Inqovi (decitabine/cedazuridine) in combination with venetoclax for newly diagnosed acute myeloid leukemia in adults aged 75 or older, or those with comorbidities precluding intensive induction chemotherapy. The approval, granted to Japan-based Taiho Oncology, Inc., expands the labeled use of Inqovi beyond its original myelodysplastic syndromes and chronic myelomonocytic leukemia indication.

The regimen combines two established AML treatment mechanisms: DNA hypomethylation through decitabine and BCL-2 inhibition through venetoclax-mediated apoptosis. Cedazuridine was specifically developed to prevent rapid gastrointestinal and hepatic degradation of oral decitabine, allowing pharmacokinetic exposure comparable to intravenous decitabine and supporting outpatient administration of an all-oral regimen for older AML patients.

The indication approval covers one Inqovi tablet — containing 35 mg decitabine and 100 mg cedazuridine — taken orally once daily on days 1 through 5 of each 28-day cycle, continued until disease progression or unacceptable toxicity, in combination with venetoclax. The prescribing information carries warnings for myelosuppression and embryo-fetal toxicity. The application was reviewed under Project Orbis, the FDA Oncology Center of Excellence’s framework for concurrent international review, with Health Canada as a collaborating partner; that application may remain under review. Inqovi holds orphan drug designation for this indication.

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Efficacy was evaluated in ASTX727-07 (NCT04657081), a single-arm, open-label Phase II trial enrolling 101 adults with newly diagnosed AML who were aged 75 or older or had comorbidities precluding intensive induction chemotherapy. The primary efficacy endpoints were complete remission rate and duration of complete remission. Of the 101 patients treated, 42 achieved complete remission, a rate of 41.6% (95% CI: 31.9, 51.8), with a median time to remission of two months. The median duration of complete remission was not reached at the time of analysis, with individual durations ranging from 0.5 to 16.3 months.

The approval positions an all-oral regimen against an established standard of care. Venetoclax combined with azacitidine — approved by the FDA in October 2020 based on the VIALE-A trial, which showed a complete remission rate of 36.7% — remains the dominant regimen in this patient population. Intravenous decitabine combined with venetoclax also carries approval in the same indication, making Inqovi plus venetoclax the oral equivalent of that backbone, differentiated primarily by its route of administration. The cedazuridine component was developed specifically to inhibit cytidine deaminase-mediated degradation of oral decitabine, enabling systemic exposure that approximates the intravenous formulation.

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