On May 20, 2022, the U.S. Food and Drug Administration (FDA) approved azacitidine (Vidaza®) for pediatric patients with newly diagnosed juvenile myelomonocytic leukemia (JMML).
Efficacy was identified in an international, multicenter, open-label study (AZA-JMML-001; NCT02447666) to evaluate the pharmacokinetics, pharmacodynamics, safety, and activity of azacitidine prior to hematopoietic stem cell transplantation (HSCT) in 18 pediatric patients with JMML. Patients were treated with IV azacitidine daily on days 1–7 of a 28-day cycle for a minimum of three and maximum of six cycles, provided patients did not experience disease progression or were ready for HSCT between cycles four and six.
The main efficacy outcome measures were clinical complete remission (cCR) or clinical partial remission (cPR) according to the International JMML response criteria at three months. Responses must have been sustained for at least four weeks either in the four-week period preceding or succeeding cycle three, day 28. Nine patients (50%, 95% CI = 26, 74) had confirmed clinical responses. Of those patients, three had cCR and six had cPR. Median time to response was 1.2 months (range = 0.95–1.87 months). The proportion of patients undergoing HSCT was 94%, and median time to HSCT was 4.6 months (range = 2.8–19 months).
The most common adverse reactions reported in more than 30% of pediatric patients with JMML were pyrexia, rash, upper respiratory tract infection, and anemia.
The recommended dose for patients aged 1 month to < 1 year or weighing less than 10 kg is 2.5 mg/kg. The recommended dose for patients aged 1 and older and weighing 10 kg or more is 75 mg/m2.
View the full prescribing information for azacitidine.
The review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved this application one month ahead of FDA’s goal date.
The application was granted priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.