Oral Azacitidine Recommended for EU Approval in AML

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has granted a positive opinion for the approval of oral azacitidine (Onureg; CC-486) as a maintenance treatment for adult patients with acute myeloid leukemia (AML) who had a complete remission (CR) or CR with incomplete blood count recovery (CRi) after induction therapy with or without consolidation treatment, and who are ineligible for or choose to not undergo hematopoietic stem cell transplant (HSCT).¹

The decision was based on findings from the international, phase 3 QUAZAR AML-001 trial, in which oral azacitidine led to a 31% reduction in the risk of death compared with placebo in this patient population; the median overall survival (OS) was 24.7 months vs 14.8 months, respectively (HR, 0.69; 95% CI, 0.55-0.86; P = .0009). The OS benefit was observed in patients who either had a CR or CRi.

Following the recommendation, the European Commission will review the data for oral azacitidine. If approved by the regulatory agency, the drug will be the first once-daily frontline oral maintenance treatment that has shown a benefit in OS in patients across AML subtypes in first remission, noted Bristol-Myers Squibb, the developer of oral azacitidine.

“Maintenance therapy options for acute myeloid leukemia that prolong overall survival have been urgently needed in Europe, especially oral options that can be taken at home. While many patients with acute myeloid leukemia achieve remission with induction therapy, responses to treatment may be of short duration and the risk of relapse remains high, especially for patients who are not eligible for stem cell transplant,” said Noah Berkowitz, MD, PhD, senior vice president, Hematology Development, Bristol Myers Squibb. “We look forward to the European Commission’s decision and to making Onureg available to appropriate patients, building on our commitment to deliver innovative therapies that improve long-term outcomes for patients.”

The European Commission is expected to deliver its decision on the approval within 67 days of receiving the CHMP opinion. If approved, the indication will be applicable to all member states in the European Union, Iceland, Norway, and Liechtenstein.

In the double-blind, randomized QUAZAR AML-001 study, investigators enrolled 472 patients who received 300 mg of oral azacitidine (n = 238) or oral placebo (n = 234) once daily for 14 days of a 28-day cycle, plus best supportive care.

To be eligible for enrollment, patients had to be at least 55 years old, have newly diagnosed AML with intermediate- or poor-risk cytogenetics, had achieved first CR or CRi following intensive induction chemotherapy with or without consolidation, and were ineligible for HSCT at time of screening. Consolidation treatment was per investigator preference prior to study entry.

Additionally, the median duration of treatment was 12 cycles (range, 1-82) for oral azacitidine and 6 cycles (range, 1-76) for placebo.

Regarding safety, serious adverse events (AEs) occurred in 15% of patients on the oral azacitidine arm; serious AEs that occurred in at least 2% of patients on this arm included pneumonia (8%) and febrile neutropenia (7%). Sepsis led to death in 1 patient on the study treatment.

Furthermore, the most common AEs on oral azacitidine vs placebo were nausea (65% vs 24%, respectively), vomiting (60% vs 10%), diarrhea (50% vs 21%), fatigue/asthenia (44% vs 25%), constipation (39% vs 24%), pneumonia (27% vs 17%), abdominal pain (22% vs 13%), arthralgia (14% vs 10%), decreased appetite (13% vs 6%), febrile neutropenia (12% vs 8%), dizziness (11% vs 9%), and pain in extremity (11% vs 5%). Treatment discontinuations on oral azacitidine due to AEs occurred in 8% of patients.

In September 2020, the FDA approved oral azacitidine for the continued treatment of adult patients with AML who achieved first CR or CR with incomplete blood count recovery following intensive induction chemotherapy who are not able to complete intensive curative therapy.²

References

1. Bristol Myers Squibb receives positive CHMP opinion for Onureg (azacitidine tablets; CC-486) as frontline oral maintenance therapy for adults with acute myeloid leukemia in first remission. News release. Bristol Myers Squibb. April 23, 2021. Accessed April 23, 2021. https://bit.ly/3axSozK
2. US Food and Drug Administration approves Onureg (azacitidine tablets), a new oral therapy, as continued treatment for adults in first remission with acute myeloid leukemia. FDA. September 1, 2020. Accessed September 1, 2020. https://bwnews.pr/2QJJsx1