Otsuka Pharmaceutical Europe Ltd. (Otsuka) and Astex Pharmaceuticals, Inc. (Astex) today announce that the European Commission (EC) has approved INAQOVI^® (oral decitabine and cedazuridine) as monotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for standard induction chemotherapy. The EC decision applies to the European Economic Area (EEA), which includes the EU member states, Iceland, Liechtenstein and Norway. INAQOVI^® is the first and only oral hypomethylating agent licensed in the EEA in this patient population.

The EC approval is based on the results from the Phase 3 ASCERTAIN clinical trial investigating the pharmacokinetic exposure equivalence of the novel oral fixed-dose combination versus intravenous (IV) decitabine in AML patients¹. The ASCERTAIN study met its primary endpoint, with the orally administered decitabine and cedazuridine fixed-dose combination showing pharmacokinetic exposure equivalence to a standard 5-day regimen of IV decitabine using a two-cycle, cross-over study design. Safety findings for the fixed-dose combination of decitabine and cedazuridine were generally consistent with those anticipated for IV decitabine¹.

The current treatment options for adults with AML range from hospital-administered IV chemotherapy infusions or, for those patients not eligible for chemotherapy, regimens based on parenterally administered hypomethylating agents, with treatment cycles typically extending for 5-7 days². Fatigue can significantly restrict daily activities and impact a patient's quality of life³. INAQOVI^® may provide both patients and physicians with an oral treatment option in this patient population.

On 10 June 2022, the European Medicines Agency (EMA) agreed to a Paediatric Investigation Plan for the oral decitabine and cedazuridine fixed-dose combination, representing an important milestone for the prospect of furthering clinical studies in children with AML.

About decitabine and cedazuridine fixed-dose combination (INAQOVI^®)

INAQOVI^® is an orally administered, fixed-dose combination of the approved hypomethylating agent (HMA), decitabine (35 mg), together with cedazuridine (100 mg), an inhibitor of cytidine deaminase^4-6. By inhibiting cytidine deaminase in the gut and liver, the fixed-dose combination is designed to allow for oral daily administration of decitabine over 5 days in a given cycle to achieve comparable systemic exposure to IV decitabine administered with the same dosing regimen⁷.

In the Phase 3 ASCERTAIN study, a total of 89 AML patients were randomised 1:1 to receive INAQOVI^® (35 mg decitabine and 100 mg cedazuridine) orally in Cycle 1 and decitabine (20 mg/m²) intravenously in Cycle 2 (n=44) or the reverse sequence (n=45). Both INAQOVI^® and IV decitabine were administered once daily on Days 1 through 5 of the 28-day cycle. Starting with Cycle 3, all patients received INAQOVI^® orally once daily on Days 1 through 5 of each 28-day cycle until disease progression, death, or unacceptable toxicity⁶.

Primary endpoint results showed that patients receiving INAQOVI^® achieved pharmacokinetic exposure equivalence of 99.64% (90% CI: 91.23, 108.8) to IV decitabine given at 20 mg/m² for 5-days with a similar pharmacodynamic activity. Secondary findings showed a Median Overall Survival of 7.9 months (95% CI: 5.9, 13.0) and a Complete Response rate of 21.8% at 7.95 months median follow up¹.

The most common adverse drug reaction (≥ 20%) was thrombocytopenia. The most common serious adverse reactions (≥ 20%) were febrile neutropenia and pneumonia. Permanent discontinuation occurred in 14% of patients while on treatment. The most frequent adverse reaction resulting in permanent discontinuation was pneumonia (5%)⁶.

About acute myeloid leukaemia (AML)

AML is the most common form of acute leukaemia in adults⁸. The median age at diagnosis is approximately 70 years². Within Europe, the incidence of AML is increasing, this may be attributed to the ageing population; AML incidence in Europe has risen from 3.48 in 1976 to 5.06 patients per 100,000 population in 2013². Across Europe and all age groups, AML is notably more common in males than in females². The outlook for patients diagnosed with AML has improved over time due to improved care and treatment, however between the years of 2000 and 2007, 5-year survival for patients was just 17%².

About Astex

Astex Pharmaceuticals, Inc. is committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies for the treatment of solid tumours and haematological malignancies. Astex is a member of the Otsuka group of companies. The group also includes Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Taiho Oncology, Inc. Subject to regulatory approvals, Astex's products will be commercialised in the U.S. and Canada by Taiho subsidiaries, and in the rest of the world by Otsuka subsidiaries.