FDA Approves Azacitidine tablets for Continued Treatment of AML

The tablets were approved for the continued treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or CR with incomplete blood count recovery (CRi) following intensive induction chemotherapy and who are not able to complete intensive curative therapy.

The FDA has approved 300 mg tablets of azacitidine (Onureg) for the continued treatment of adult patients with acute myeloid leukemia (AML) who achieved first complete remission (CR) or CR with incomplete blood count recovery (CRi) following intensive induction chemotherapy and who are not able to complete intensive curative therapy, according to Bristol Myers Squibb, the developer of the agent.

The approval was based on results from the pivotal phase 3 QUAZAR AML-001 study in which treatment with azacitidine tablets resulted in a statistically significant and clinically meaningful improvement in overall survival (OS), the study’s primary end point, of almost 10 months compared to placebo. Results from the study were first presented at the American Society of Hematology (ASH) Annual Meeting in December 2019.

“Continued treatment with [azacitidine tablets] demonstrated an overall survival benefit in adults with AML who had achieved first complete remission in the QUAZAR AML-001 study and, notably, it has the potential to do this in a convenient manner, given its once daily oral formulation,” Andrew Wei, MBBS, PhD, QUAZAR AML-001 lead investigator from Alfred Hospital and Monash University in Melbourne, Australia, said in a press release. “This approval should help establish continued treatment with [azacitidine tablets] as a standard component of AML therapy for adults who achieved first complete remission following chemotherapy and who cannot proceed to intensive curative therapy, like hematopoietic stem cell transplant.”

The phase 3, international, randomized, double-blind study enrolled patients who were 55 years or older, had AML, were within 4 months of achieving first CR or CRi following intensive induction chemotherapy with or without consolidation treatment (per investigator preference prior to study entry), and were not candidates for hematopoietic stem cell transplant (HSCT) at the time of screening. Overall, the study enrolled 472 patients who were randomized 1:1 to receive either 300 mg of azacitidine tablets (n = 238) or placebo (n = 234) orally, once daily, for 14 days of a 28-day cycle, plus best supportive care.

Median OS from time of randomization was greater than 2 years (24.7 months; 95% CI, 18.7-30.5) among patients who received azacitidine tablets compared to 14.8 months (95% CI, 11.7-17.6) among patients receiving placebo (HR, 0.69; 95% CI, 0.55-0.86; P = .0009). Notably, the azacitidine tablets were continued until disease progression or unacceptable toxicity.

Serious adverse events (AEs) occurred in 15% of patients who received azacitidine tablets. Serious AEs observed in at least 2% of patients who received the agent included pneumonia (8%) and febrile neutropenia (7%). Only 1 fatal adverse reaction (sepsis) occurred in a patient who received azacitidine tablets.

The most common adverse events observed with azacitidine tablets versus 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%). Moreover, of those who received azacitidine, permanent discontinuation due to an AE occurred in 8% of patients.

“The FDA approval of [azacitidine tablets] is the culmination of over a decade of research and 13 pre-clinical and clinical trials. We are grateful to the patients, families and caregivers who participated in and supported these trials, and who ultimately made today’s advancement possible,” Giovanni Caforio, MD, chairman and chief executive officer, Bristol Myers Squibb, said in the release. “This milestone is representative of our commitment to helping patients with hard-to-treat cancers live longer, and the approval of [azacitidine tablets] as an oral therapy option for patients is more relevant now than ever as the world continues to navigate the COVID-19 pandemic.”

Importantly, Bristol Myers Squibb indicated that azacitidine tablets have warnings and precautions for risks of substitution with other azacitidine products, myelosuppression, increased early mortality in patients with myelodysplastic syndromes (MDS) and embryo-fetal toxicity. Due to substantial differences in the pharmacokinetic parameters, the company indicated azacitidine tablets should not be substituted for intravenous or subcutaneous azacitidine as it may result in a fatal adverse reaction.

The new drug application for this indication was previously granted priority review designation by the FDA, and a marketing authorization application for this indication was validated by the European Medicines Agency in May 2020.


U.S. Food and Drug Administration Approves Onureg® (azacitidine tablets), a New Oral Therapy, as Continued Treatment for Adults in First Remission with Acute Myeloid Leukemia [news release]. Princeton, NJ. Published September 1, 2020. Accessed September 1, 2020. https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-approves-onureg-azacitidine-ta

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