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

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The large, multicenter QUAZAR® AML-001 trial established the efficacy and safety of the first and only FDA-approved continued treatment for AML1,2

QUAZAR® AML-001 was designed to evaluate ONUREG® vs placebo as continued treatment for adult patients in first CR/CRi1

The efficacy of ONUREG® was established on the basis of overall survival The efficacy of ONUREG® was established on the basis of overall survival
Baseline Demographics

The QUAZAR® AML-001 trial enrolled a broad AML population1

Select baseline demographics and disease-related characteristics in the QUAZAR® AML-001 trial1

Select baseline demographics and disease-related characteristics in the QUAZAR® AML-001 trial Select baseline demographics and disease-related characteristics in the QUAZAR® AML-001 trial

ECOG, Eastern Cooperative Oncology Group.

*Intermediate risk was defined as normal cytogenetics +8, t(9;11), or other undefined.
†Poor risk was defined as complex (≥3 abnormalities): -5; 5q-; -7; 7q-; 11q23 - non t(9;11); inv(3); t(3;3); t(6;9); or t(9;22).
‡For this measure, ONUREG® (n=237) and placebo (n=232).
Source for Intermediate and Poor Risk: Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.2.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed June 14, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Efficacy Results

ONUREG®: Over 2 years OS and extended follow-up data1,6*

Kaplan-Meier curve for OS: ITT population in QUAZAR® AML-0011

Kaplan-Meier curve for OS: ITT population in QUAZAR® AML-001 Kaplan-Meier curve for OS: ITT population in QUAZAR® AML-001

CI, confidence interval; ITT, intention-to-treat.

*ONUREG® (95% CI: 18.7, 30.5); placebo (95% CI: 11.7, 17.6).

†The HR is from a Cox proportional hazards model stratified by age (55 to 64 vs ≥65 years), cytogenetic risk category at time of induction therapy (intermediate risk vs poor risk), and received consolidation therapy (yes vs no).

‡HR for initial follow-up was 0.69 (95% Cl: 0.55, 0.86; P=0.0009).

Graph showing median OS for ONUREG® versus placebo Graph showing median OS for ONUREG® versus placebo

*ONUREG® (95% Cl: 18.7, 30.5); placebo (95% Cl: 11.7, 17.6).

†The HR is from a Cox proportional hazards model stratified by age (55 to 64 vs ≥65 years), cytogenetic risk category at time of induction therapy (intermediate risk vs poor risk), and received consolidation therapy (yes vs no).

‡HR for initial follow-up was 0.69 (95% Cl: 0.55, 0.86; P=0.0009).

CI, confidence interval; ITT, intention-to-treat.

Half of patients who received ONUREG® were still alive at 2 years5,6

QUAZAR® AML-001 survival estimates

QUAZAR® AML-001 survival estimates QUAZAR® AML-001 survival estimates

Kaplan-Meier methods are used to estimate the 1-year, 2-year, and 3-year survival probabilities.

Primary endpoint subgroup analysis: treatment with ONUREG® across subgroups vs placebo for median overall survival5,7

OS select subgroup analysis

OS select subgroup analysis OS select subgroup analysis

aNumber of events/number of subjects.

bMedian OS in months.

cPrior MDS and CMML.

ONUREG® patients with an NPM1 mutation had ~4 years median OS4,6

Kaplan-Meier curve for OS: patients with an NPM1 mutation in QUAZAR® AML-001*

The NPM1 mutation, which is prognostically favorable, occurs in ~30% of patients with AML (based on an analysis of 1540 AML patients from 3 prospective multicenter trials).8

QUAZAR® AML-001 retrospective, post hoc subgroup analysis4

28% (66/236) of patients who received ONUREG® and 30% (71/233) of patients who received placebo had an NPM1 mutation at diagnosis.6

Analysis limitations

  • Retrospective, exploratory, subgroup analyses of QUAZAR® AML-001 included an assessment of NPM1 mutation status at diagnosis and its impact on survival outcome
  • These diagnostic analyses were obtained from local investigator reports and were not confirmed by central lab assessment. Of the 472 randomized patients, 469 were evaluable for the mutation
  • This survival analysis should not be interpreted to determine a treatment difference between arms in these select endpoints because of potential selection bias, small sample size, and it was not statistically powered
Kaplan-Meier curve for OS: patients with an NPM1 mutation in QUAZAR® AML-001 Kaplan-Meier curve for OS: patients with an NPM1 mutation in QUAZAR® AML-001

*HR 0.63 (95% CI: 0.41, 0.98).8

†ONUREG® (95% CI: 34.3, NA); placebo (95% CI: 11.7, 44.1).6
NA, not available.

Safety

INDICATION

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

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ONUREG® is contraindicated in patients with known severe hypersensitivity to azacitidine or its components.

WARNINGS AND PRECAUTIONS

Risks of Substitution with Other Azacitidine Products

Due to substantial differences in the pharmacokinetic parameters, the recommended dose and schedule for ONUREG® are different from those for the intravenous or subcutaneous azacitidine products. Treatment of patients using intravenous or subcutaneous azacitidine at the recommended dosage of ONUREG® may result in a fatal adverse reaction. Treatment with ONUREG® at the doses recommended for intravenous or subcutaneous azacitidine may not be effective. Do not substitute ONUREG® for intravenous or subcutaneous azacitidine.

Myelosuppression

New or worsening Grade 3 or 4 neutropenia and thrombocytopenia occurred in 49% and 22% of patients who received ONUREG®. Febrile neutropenia occurred in 12%. A dose reduction was required for 7% and 2% of patients due to neutropenia and thrombocytopenia. Less than 1% of patients discontinued ONUREG® due to either neutropenia or thrombocytopenia. Monitor complete blood counts and modify the dosage as recommended. Provide standard supportive care, including hematopoietic growth factors, if myelosuppression occurs.

Increased Early Mortality in Patients with Myelodysplastic Syndromes (MDS)

In AZA-MDS-003, 216 patients with red blood cell transfusion-dependent anemia and thrombocytopenia due to MDS were randomized to ONUREG® or placebo. 107 received a median of 5 cycles of ONUREG® 300 mg daily for 21 days of a 28-day cycle. Enrollment was discontinued early due to a higher incidence of early fatal and/or serious adverse reactions in the ONUREG® arm compared with placebo. The most frequent fatal adverse reaction was sepsis. Safety and effectiveness of ONUREG® for MDS have not been established. Treatment of MDS with ONUREG® is not recommended outside of controlled trials.

Embryo-Fetal Toxicity

ONUREG® can cause fetal harm when administered to a pregnant woman. Azacitidine caused fetal death and anomalies in pregnant rats via a single intraperitoneal dose less than the recommended human daily dose of oral azacitidine on a mg/m2 basis. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ONUREG® and for at least 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ONUREG® and for at least 3 months after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurred in 15% of patients who received ONUREG®. Serious adverse reactions in ≥2% included pneumonia (8%) and febrile neutropenia (7%). One fatal adverse reaction (sepsis) occurred in a patient who received ONUREG®.

Most common (≥10%) adverse reactions with ONUREG® vs placebo were nausea (65%, 24%), vomiting (60%, 10%), diarrhea (50%, 21%), fatigue/asthenia (44%, 25%), constipation (39%, 24%), pneumonia (27%, 17%), abdominal pain (22%, 13%), arthralgia (14%, 10%), decreased appetite (13%, 6%), febrile neutropenia (12%, 8%), dizziness (11%, 9%), pain in extremity (11%, 5%).

LACTATION

There are no data regarding the presence of azacitidine in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with ONUREG® and for 1 week after the last dose.

Please see full Prescribing Information for ONUREG®.

References:
  1. ONUREG® [Prescribing Information]. Summit, NJ: Celgene Corporation; 2021.
  2. Burnett A, Wetzler M, Löwenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011;29(5):487-494.
  3. Büchner T, Berdel WE, Haferlach C, et al. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol. 2009;27(1):61-69.
  4. Röllig C, Kramer M, Gabrecht M, et al. Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients. Ann Oncol. 2018;29(4):973-978.
  5. Brinda B, Khan I, Parkin B, Konig H. The rocky road to personalized medicine in acute myeloid leukaemia. J Cell Mol Med. 2018;22(3):1411-1427.
  6. SEER Cancer Statistics Review 1975-2017. National Cancer Institute website. https://seer.cancer.gov/csr/1975_2017/. Accessed August 28, 2020.
  7. Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(26):2526-2537.
  8. ONUREG® [Prescribing Information]. Summit, NJ: Celgene Corporation; 2021.
  9. Sekeres MA, Guyatt G, Abel G, et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv. 2020;4(15):3528-3549.
  10. Medeiros BC, Satram S. Real world treatment patterns and comparative effectiveness among elderly patients with acute myeloid leukemia in the United States. Ann Hematol Oncol. 2020;7(1):1283.
  11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.2.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed June 14, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  12. Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. New Engl J Med. 2015;373:1136-1152.
  13. Hamadani M, Craig M, Awan FT, Devine SM. How we approach patient evaluation for hematopoietic stem cell transplantation. Bone Marrow Transplant. 2010;45:1259-1268.
  14. Klepin HD, Estey E, Kadia T. More versus less therapy for older adults with acute myeloid leukemia: new perspectives on an old debate. Am Soc Clin Oncol Educ Book. 2019;39:421-432.
  15. Lipof JJ, Loh KP, O’Dwyer K, Liesveld JL. Allogeneic hematopoietic cell transplantation for older adults with acute myeloid leukemia. Cancers (Basel). 2018;10(6):179.
  16. 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 [press release]. Bristol Myers Squibb website. https://news.bms.com/news/corporate-financial/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/default.aspx. Published September 1, 2020. Accessed July 21, 2021.
  17. 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 [press release]. Bristol Myers Squibb website. https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-approves-onureg-azacitidine-ta. Published September 1, 2020. Accessed September 1, 2020.
  18. Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(Suppl):1-25.
  19. Döhner H, Wei AH, Roboz GJ, et al. Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacytidine. Blood. 2022;140(15):1674-1685.
  20. Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(26):2526-2537.
  21. Data on file, Celgene Corporation. Summit, New Jersey.
  22. Wei AH, Döhner H, Pocock C, et al. The QUAZAR AML-001 maintenance trial: results of a phase III international, randomized, double-blind, placebo-controlled study of CC-486 in patients with acute myeloid leukemia (AML) in first remission [oral presentation at ASH 2019]. Blood. 2019;134(Suppl 2):LBA-3.
  23. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209-2221.
  24. Ravandi F, Roboz GJ, Wei AH, et al. Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial. J Hematol Oncol. 2021;14(1):133.