FDA Approves CC-486 as Maintenance Therapy in Acute Myeloid Leukemia


The FDA granted approval to the oral hypomethylating agent, CC-486 (azacitidine tablets, Onureg), as a maintenance treatment for adult patients with acute myeloid leukemia who achieved a first complete remission or with incomplete blood count recovery after intensive induction chemotherapy and who are unable to complete intensive curative therapy.


The FDA granted approval to the oral hypomethylating agent, CC-486 (azacitidine tablets, Onureg), as a maintenance treatment for adult patients with acute myeloid leukemia (AML) who achieved a first complete remission (CR) or CR with incomplete blood count recovery (CRi) after intensive induction chemotherapy and who are unable to complete intensive curative therapy, such as hematopoietic stem cell transplant (HSCT).1

“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,” lead investigator Andrew Wei, MBBS, PhD, of the Alfred Hospital and Monash University, Melbourne, Australia, said in a statement. “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.”

Approval was granted to CC-486 on the basis of data from the phase 3 QUAZAR AML-001 clinical trial (NCT0175753). QUAZAR is an international, randomized, double-blind, placebo-controlled study evaluating the agent as maintenance therapy in patients aged 55 years and above who are in their first AML remission, following induction therapy.

The goal of QUAZAR AML-001was to help patients with AML sustain therapeutic activity after intensive induction chemotherapy, which historically has a temporary response and poor overall survival (OS).

In the study, 472 patients received either CC-486 at a dose level of 300 mg or placebo once daily for 14 days of a 28-day cycle. Treatment was administered along with best supportive care. All drugs in the study were given until unacceptable toxicity or disease progression.

Baseline screening showed that the median age 68 years old (range, 55-86). All patients had newly diagnosed and histologically confirmed AML, de novo, or secondary AML that was secondary to prior myelodysplastic syndrome or chronic myelomonocytic leukemia.

Median follow-up in the study was 41.2 months. The median overall survival (OS) was 24.7 months with CC-486 compared with 14.8 months with placebo. The difference in OS was significant (HR, 0.69; 95% CI, 0.55-0.86; P = .0009). CC-486 also led to a significant extension in relapse-free survival (RFS), which was 10.2 months in the experimental arm compared with 4.8 months in the control arm (HR, 0.65; 95% CI, 0.52-0.81; P = .0001). The efficacy benefit of CC-486 was observed regardless of patients’ baseline characteristics or CR/CRi status. Also, health-related quality of life outcomes were not negatively impacted by treatment with CC-486.2

Patients were exposed to the experimental drug for 12 cycles (range 1-80) and placebo exposure was for 6 cycles (range, 1-73). The most frequent grade 1/2 adverse events (AEs) reported in the CC-486 arm versus the placebo arm were gastrointestinal (GI) events, including nausea (64% and 23%, respectively), vomiting (59% and 10%), and diarrhea (49% and 21%), respectively.

Grade 3/4 AEs occurred in 41% of the patients who received CC-486 and 24% of those who received placebo, with the most common being thrombocytopenia (23% and 22%), and anemia (14% and 13%), respectively.

Serious AEs were also observed in the study and occurred in 17% of the CC-486 arm versus 8% of the placebo arms. Thirteen percent of patients in the CC-486 arm and 4% in the placebo arm discontinued treatment due to AE, and more the majority of these patients, the cause was GI events.

In addition to hypomethylation of DNA and RNA, CC-486 also has the ability to direct cytotoxicity to abnormal hematopoietic cells in the bone marrow. This mechanism restores the function in some genes, ultimately prolonging therapeutic effects.

“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, MD, chairman and CEO, Bristol Myers Squibb, in a statement. “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 [coronavirus disease 2019] pandemic.”


1. 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. Bristol Myers Squibb. September 1, 2020. Accessed September 1, 2020. https://bit.ly/31LAuWu

2. Wei A, Dohner 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 (Oral Formulation of Azacitidine) in Patients with Acute Myeloid Leukemia (AML) in First Remission. Blood. 2019;134(suppl 2): LBA3. doi:10.1182/blood-2019-132405.

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