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Inaqovi, oral combination of Decitabine and Cedazuridine, for the treatment of adults with newly diagnosed acute myeloid leukaemia. European Commission has approved

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 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 patients with acute myeloid leukaemia.
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 Decitabine.

The current treatment options for adults with acute myeloid leukaemia 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 days.
Fatigue can significantly restrict daily activities and impact a patient's quality of life.
Inaqovi may provide both patients and physicians with an oral treatment option in this patient population.

Inaqovi is an orally administered, fixed-dose combination of the approved hypomethylating agent, Decitabine ( 35 mg ), together with Cedazuridine ( 100 mg ), an inhibitor of cytidine deaminase. 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 regimen.

In the phase 3 ASCERTAIN study, a total of 89 patients with acute myeloid leukaemia 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 toxicity.

Primary endpoint results have shown that patients receiving Inaqovi have 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 have shown a median overall survival ( OS ) of 7.9 months ( 95% CI: 5.9, 13.0 ) and a complete response ( CR ) rate of 21.8% at 7.95 months median follow up.

The most common adverse drug reaction ( greater than or equal to 20% ) was thrombocytopenia. The most common serious adverse reactions ( greater than or equal to 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% ).

Acute myeloid leukaemia is the most common form of acute leukaemia in adults. The median age at diagnosis is approximately 70 years. Within Europe, the incidence of acute myeloid leukaemia is increasing, this may be attributed to the ageing population; acute myeloid leukaemia incidence in Europe has risen from 3.48 in 1976 to 5.06 patients per 100,000 population in 2013. Across Europe and all age groups, acute myeloid leukaemia is notably more common in males than in females. The outlook for patients diagnosed with acute myeloid leukaemia 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%. ( Xagena )

Source: Otsuka Pharmaceutical, 2023