Janssen-Cilag International NV (Janssen) announced today that the European Commission has approved the marketing authorisation for DACOGEN® (decitabine) for the treatment of adult patients (age 65 years and above) with newly diagnosed de novo or secondary acute myeloid leukaemia (AML), according to the World Health Organisation (WHO) classification, who are not candidates for standard induction chemotherapy. DACOGEN® also has Orphan Drug designation for the treatment of AML.
The data in support of the marketing authorization is based on the Phase III DACO-016 trial that compared decitabine to a patient’s choice with physician advice of either supportive care or low-dose cytarabine in the treatment of older patients with AML. The analysis of the protocol-specified results demonstrated an increase of 54 percent in median overall survival in patients taking decitabine (7.7 months for decitabine patients, compared to 5.0 months for patients in the comparator arm; HR=0.85, 95 percent CI: 0.69 to 1.04, p=0.108). An updated analysis of mature survival data confirmed this strong trend for improved overall survival and provided clinically significant evidence of decitabine efficacy (HR=0.82; 95 percent CI: 0.68 to 0.99; nominal p=0.037).
Dr. Xavier G. Thomas of the Hospital Edouard Herriot in Lyon, France, one of the lead DACO-016 investigators, comments: "AML is a life-threatening disease that is very difficult to treat. DACOGEN® is proven to offer a clinically relevant overall survival advantage compared to standard therapies and has no major differences in safety. This is wonderful news for older patients that may not be able to tolerate standard induction therapy."
DACO-016, with 485 study subjects, is the largest AML trial to date in older patients. It was a Phase III, randomized, open-label trial, in newly diagnosed patients ≥65 years of age with de novo or secondary AML and poor- or intermediate-risk cytogenetics. Patients were enrolled globally at 65 clinical sites. Of the 485 patients, 242 were randomized to decitabine and 243 to patient's treatment choice of supportive care or low-dose cytarabine (majority of patients, 88%). Patients treated with decitabine received a 1-hour infusion, once daily for 5 consecutive days every 4 weeks. Patients treated with cytarabine received 20 mg/m2 subcutaneously once daily 10 consecutive days every 4 weeks. The median duration of treatment for patients on decitabine arm was 4.4 months, compared with 2.4 months in the cytarabine group.
Adverse events (AEs) were consistent with the known decitabine safety profile and without major differences between the treatment arms. The most frequently reported Grade 3 or 4 hematologic AEs were thrombocytopenia, anemia, neutropenia, and febrile neutropenia.
"We are thrilled to offer this new option to older AML patients in Europe," commented Peter Lebowitz, MD, PhD, Oncology Therapeutic Area Head, Janssen R&D. "DACOGEN® nicely complements our growing portfolio of therapies to treat haematologic malignancies, which is one of our key areas of focus in oncology."
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