Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults with a median age of 70 years, accounting for approximately 80% of cases in this population group. Current treatment options for AML patients who are not suitable for intensive chemotherapy are administered parenterally. After a diagnosis of AML, patients spend more than 40% of their life in the hospital or in outpatient clinics, so an oral formulation is an alternative to current options.
In this context, INAQOVI® (oral decitabine and cedazuridine) has landed in Spain, the first oral monotherapy treatment for adult patients with newly diagnosed AML who are not candidates for standard induction chemotherapy. The Ministry of Health, following the agreement of the Interministerial Commission on Drug Prices (CIPM), has approved the financing of the drug in the National Health System, which has been available in Spain since September 2.
Public funding in Spain follows authorisation by the European Commission (EC) in September 2023. The EC’s positive opinion was based on positive results from the Phase III ASCERTAIN trial, which assessed the equivalence of pharmacokinetic exposure of the novel oral fixed-dose combination compared to intravenous (IV) decitabine in patients with AML. The ASCERTAIN study met its primary endpoint, with the oral fixed-dose combination of decitabine and cedazuridine showing equivalence of pharmacokinetic exposure to a standard five-day regimen of IV decitabine using a two-cycle crossover study design. Safety findings for the fixed-dose combination of decitabine and cedazuridine were generally consistent with those expected for IV decitabine.
Potential benefits of new oral treatment versus intravenous therapy
“There is a significant unmet need for AML patients to have effective targeted treatments that are less toxic than the available chemotherapy regimens. With this new oral therapeutic option, people with AML, who are mostly elderly, will be able to be treated more comfortably and easily from home, which can also prevent potential complications resulting from hospital admission or transfer to the hospital to receive parenteral treatment on consecutive days,” said Lluïsa Arbat, medical director of Otsuka Pharmaceutical in Spain.
Dr. Adolfo de la Fuente, head of the Hematology and Hemotherapy Service at the MD Anderson Cancer Center Hospital in Madrid, explains that patients with acute myeloid leukemia “face serious problems such as infections due to the weakness of their immune system and severe anemia, which contributes to fatigue and weakness. These symptoms and complications generate a considerable physical and emotional burden. In this context, oral treatments emerge as an alternative that offers multiple advantages, maintaining a high effectiveness of the treatment and increasing the quality of life.”
Unlike intravenous treatments, Dr. De la Fuente points out, “oral medications can be taken at home, which reduces the need for hospital visits and hospital admissions. This not only makes the patient’s daily life easier, but also reduces the disruption to their daily and work activities. The patient spends more time in their own environment, which is often less stressful than constant hospital visits.” In short, he concludes, “oral treatments for acute myeloid leukemia not only represent a clinical advance, but also provide tangible benefits in the daily life of patients, allowing for greater comfort and quality of life.”
Acute myeloid leukemia is a malignant hematopoietic neoplasm of bone marrow stem cells, which presents abnormal differentiation and clonal accumulation of myeloid stem cells. After diagnosis, patients with AML are classified according to their cytogenetic risk and physical fitness status to establish the most appropriate treatment course.
In current clinical practice, it is estimated that just over 50% of patients diagnosed with AML are not candidates for intensive induction chemotherapy. Adult patients with AML who are not candidates for intensive induction chemotherapy are patients who have, from the outset, a worse prognosis compared to those who are candidates, due to an older age, a greater number of comorbidities or unfavorable biological characteristics.
Despite advances in treatment options for AML, the prognosis for older patients (age ≥60 years) remains poor. In 2015, approximately 60% of older patients with AML were not receiving treatment. The average survival rate for elderly patients is less than 2 years.
Although HRQoL data specific to adult AML patients not eligible for intensive induction CT are limited, it is estimated that HRQoL in these patients is worse than that compared to the general AML population due to their older age, greater presence of comorbidities, and worse overall prognosis.
Current treatments for this group of patients are administered parenterally for 5-7 days/treatment cycle every 28 days. This means that after receiving a diagnosis of AML, patients spend more than 40% of their life in hospital or attending outpatient appointments.
An oral treatment option may provide a therapeutic advance over current therapy, allowing the patient to be treated at home and reducing the burden of multiple monthly intravenous or subcutaneous treatments in a clinical/hospital setting.
The new treatment is an orally administered fixed-dose combination of the hypomethylating antineoplastic agent decitabine (35 mg) together with cedazuridine (100 mg), a cytidine deaminase inhibitor. 13-14 By inhibiting cytidine deaminase in the gut and liver, the fixed-dose combination is designed to allow daily oral administration of decitabine for 5 days in a 28-day cycle to achieve systemic exposure comparable to IV decitabine administered at the same dosing regimen.
On 10 June 2022, the European Medicines Agency (EMA) agreed on a Paediatric Investigation Plan for the oral fixed-dose combination of decitabine and cedazuridine, representing an important milestone in the prospect of advancing clinical studies in children with AML.
Source: Otsuka
