Otsuka Pharmaceutical Europe has submitted a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for the combination therapy of oral decitabine and cedazuridine (Inaqovi) with venetoclax for the treatment of adults with newly diagnosed acute myeloid leukaemia (AML) who are not eligible for standard induction chemotherapy.

AML is a cancer of the bone marrow and blood that develops when mutations affect genes or chromosomes controlling cell growth. It is the most common type of acute leukaemia and is primarily diagnosed in adults over 60. Across Europe, AML incidence continues to rise, and the five-year survival rate for adults remains around 17%.

The EMA submission is supported by data from the Phase 1/2 Ascertain-V study, which evaluated the safety and efficacy of the all-oral decitabine-cedazuridine and venetoclax regimen in patients with newly diagnosed AML who cannot undergo standard induction chemotherapy. The trial met its primary endpoint, achieving complete remission (CR) in 46.5% of participants at a median of 2.4 months. Among those who achieved CR, 80% maintained remission at six months and 75.3% at 12 months.

The combination demonstrated safety, response and survival outcomes consistent with established parenteral azacitidine plus venetoclax regimens. The most frequent grade 3 or higher adverse events were anaemia (38.6%), neutropenia (35.6%) and febrile neutropenia (49.5%), while 30-day and 60-day mortality rates were 3.0% and 9.9%, respectively.

An Otsuka spokesperson said: “This submission represents an important step in expanding access to oral options for patients with AML who are often unable to tolerate intensive chemotherapy. We are working closely with the EMA to make this potential treatment available as soon as possible.”

The application follows acceptance of a supplemental new drug application by the US Food and Drug Administration in July 2025. The treatment was first authorised in Europe in 2023 for newly diagnosed AML in patients not eligible for standard induction chemotherapy.

Inaqovi is an oral fixed-dose combination of decitabine (35 mg), a hypomethylating agent, and cedazuridine (100 mg), a cytidine deaminase inhibitor. By blocking cytidine deaminase in the gut and liver, the combination allows oral administration of decitabine over five days per treatment cycle, achieving systemic exposure comparable to intravenous dosing.

In the Phase 3 Ascertain trial, 89 patients with AML were randomised to receive either oral Inaqovi or intravenous decitabine in alternating cycles. The study confirmed pharmacokinetic equivalence of 99.64% (90% CI: 91.23–108.8) between oral and intravenous formulations and showed a median overall survival of 8.9 months with a complete response rate of 21.8%.

The most common adverse reactions were thrombocytopenia, febrile neutropenia and pneumonia. Permanent discontinuation occurred in 14% of patients, most frequently due to pneumonia.