On May 20, the U.S. Food and Drug Administration approved azacitidine (Vidaza) for pediatric patients with newly diagnosed juvenile myelomonocytic leukemia (JMML).
Efficacy was evaluated in AZA-JMML-001 (ClinicalTrials.gov identifier NCT02447666), an international, multicenter, open-label study to evaluate the pharmacokinetics, pharmacodynamics, safety, and activity of azacitidine prior to hematopoietic stem cell transplantation (HSCT) in 18 pediatric patients with juvenile myelomonocytic leukemia. Patients were treated with intravenous azacitidine daily on days 1 to 7 of a 28-day cycle for a minimum of three cycles and a maximum of six cycles, provided patients did not have disease progression or were ready for HSCT between cycles 4 and 6.
The main efficacy outcome measures were clinical complete remission or clinical partial remission according to the International JMML response criteria at 3 months (cycle 3, day 28). Responses must have been sustained for at least 4 weeks either in the 4-week period preceding or succeeding cycle 3, day 28. A total of nine patients (50%, 95% confidence interval = 26%–74%) had confirmed clinical responses. Of these nine patients, there were three clinical complete remissions and six clinical partial remissions. The median time to response was 1.2 months (range = 0.95–1.87 months). The proportion of patients undergoing HSCT was 94% and the median time to HSCT was 4.6 months (range = 2.8–19 months).
The most common adverse reactions (> 30%) occurring in pediatric patients with juvenile myelomonocytic leukemia were pyrexia, rash, upper respiratory tract infection, and anemia.
The recommended dose for patients aged 1 month to less than 1 year or weighing less than 10 kg is 2.5 mg/kg. The recommended dose for patients at least 1 year old and weighing ≥ 10 kg is 75 mg/m2.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 1 month ahead of the FDA goal date.
This application was also granted Priority Review and Breakthrough Designation.