Bristol Myers Squibb Onureg gets USFDA approval to treat Acute Myeloid Leukemia

Onureg, the first and only FDA-approved continued AML therapy for patients in remission, is an oral hypomethylating agent that incorporates into DNA and RNA. The main mechanism of action is thought to be hypomethylation of DNA, as well as direct cytotoxicity to abnormal hematopoietic cells in the bone marrow. Hypomethylation may restore normal function to genes that are critical for cell differentiation and proliferation.7,8

The approval is based on results from the pivotal Phase 3 QUAZAR AML-001 study in which treatment with Onureg resulted in a statistically significant and clinically meaningful improvement in overall survival (OS), the study's primary endpoint, of nearly 10 months compared to placebo. Median OS from time of randomization was greater than two years (24.7 months; 95% Confidence Interval [CI]: 18.7 to 30.5) among patients who received Onureg compared to 14.8 months (95% CI: 11.7 to 17.6) among patients receiving placebo (Hazard Ratio [HR]: 0.69, 95% CI: 0.55 to 0.86; p=0.0009).

Onureg was continued until disease progression or unacceptable toxicity. Onureg has 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, Onureg should not be substituted for intravenous or subcutaneous azacitidine as it may result in a fatal adverse reaction. New or worsening Grade 3 or 4 neutropenia and thrombocytopenia occurred in 49% and 22% of patients who received Onureg, respectively. Febrile neutropenia occurred in 12% of patients. Complete blood counts should be monitored, dosing should be modified as recommended and standard supportive care should be provided if myelosuppression occurs. Enrollment was discontinued early in the study AZA-MDS-003 due to a higher incidence of early fatal and/or serious adverse reactions in the Onureg arm compared with the placebo arm. Treatment of MDS with Onureg is not recommended outside of controlled trials. Onureg can cause fetal harm when administered to a pregnant woman.

"Continued treatment with Onureg 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,"1 said Andrew Wei, MBBS, Ph.D., QUAZAR AML-001 lead investigator, Alfred Hospital and Monash University, Melbourne, Australia. "This approval should help establish continued treatment with Onureg 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 FDA approval of Onureg 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," said Giovanni Caforio, M.D., chairman and chief executive officer, Bristol Myers Squibb. "This milestone is representative of our commitment to helping patients with hard-to-treat cancers live longer, and the approval of Onureg as an oral therapy option for patients is more relevant now than ever as the world continues to navigate the COVID-19 pandemic."

The New Drug Application was granted Priority Review Designation by the FDA, and a Marketing Authorization Application (MAA) for this indication was validated by the European Medicines Agency in May 2020.

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