Know Your Therapy: Onureg (azacitidine)

What is Onureg and how does it work in treating acute myeloid leukemia?

Onureg is a medication that was approved by the FDA in September 2020. It is oral azacitidine, a hypomethylating agent that has been approved for over a decade for the treatment of myelodysplastic syndrome and acute myeloid leukemia (AML). Oral azacitidine is a newer formulation of azacitidine, which had historically been given through IV or injection. As a hypomethylating agent, it helps turn back on genes that suppress tumor or cancer cells so they can become more active in patients with leukemia. Onureg is a pill form of azacitidine, but it works differently than subcutaneous or intravenous azacitidine, and its approval was also based on different clinical data.

Who is typically prescribed Onureg, and at what stage of AML treatment is it used?

Onureg is approved for continued or maintenance therapy for adult patients with AML after undergoing intensive induction chemotherapy and achieving complete remission. It is intended for patients who cannot continue further intensive chemotherapy due to illness or complications from the initial induction cycle. Oral azacitidine is prescribed for patients who have been treated with intensive induction and consolidation therapy and are in remission. It is used as maintenance therapy to keep patients in remission longer and improve survival, especially for those who aren’t candidates for a stem cell transplant.

Approval for Onureg was based on the QUAZAR study in AML, which included patients 55 years or older who achieved complete remission or complete remission with incomplete count recovery. These patients had no evidence of leukemia in their bone marrow after intensive chemotherapy and up to 1–3 cycles of post-remission therapy. Ideally, patients would have undergone an allogeneic stem cell transplant but were unable to do so due to comorbidities, lack of donor, or personal choice. In the study, half the patients received placebo and half received Onureg. The dosing schedule was two weeks on, two weeks off, in a 28-day cycle. Onureg demonstrated about a ten-month improvement in overall survival over placebo, leading to FDA approval as the first maintenance therapy for AML.

How is Onureg administered?

Onureg is taken orally as a pill, typically daily for 14 days, followed by a 14-day break, making a 28-day cycle. It is continued as long as it is effective, the patient remains in remission, and they can tolerate the treatment. Patients usually have lab work monitored at least once a month to ensure disease stability. Onureg comes in two pill strengths—300 mg and 200 mg. The typical starting dose is 300 mg two weeks on, two weeks off, which can be adjusted to 200 mg or altered schedules depending on tolerability and toxicity. Currently, Onureg is approved only as a single-agent therapy and cannot be substituted with IV or subcutaneous azacitidine.

What are the side effects of Onureg?

The majority of side effects are gastrointestinal, including nausea, vomiting, diarrhea, and changes in taste. Anti-nausea medications are usually prescribed before each dose, and treatments like Imodium may be used for diarrhea. Other side effects include myelosuppression, resulting in lower blood counts such as platelets and white blood cells, joint aches, fatigue, and an increased risk of pneumonia or lung infections. With dose modifications and preventative medications, many patients tolerate Onureg well.

How long does someone with AML take Onureg?

Onureg is taken indefinitely for patients in remission, until there are signs of relapse, intolerance, or patient choice to stop. In clinical studies, the median survival duration with Onureg was 25 months, compared to 15 months for placebo, showing a ten-month improvement in overall survival.

How is the effectiveness of Onureg monitored?

Effectiveness is monitored through regular blood counts to ensure stability and check for signs of relapse. Peripheral blood counts are used to detect the reappearance of leukemic blasts. If abnormalities are detected without explanation, a bone marrow biopsy may be performed to assess disease status.

Can Onureg cure AML?

Oral azacitidine is not curative for AML. It is intended to prolong remission and help patients live longer. For most patients, leukemia is expected to eventually relapse. Onureg is approved as maintenance therapy to prevent relapse and prolong survival, especially for patients who otherwise would undergo a transplant, which is the curative option for higher-risk disease. Approval is particularly for patients with intermediate- or high-risk cytogenetic abnormalities.

How is Onureg different from other hypomethylating agents?

Other hypomethylating agents in AML, such as IV or subcutaneous azacitidine and decitabine, are not interchangeable with oral azacitidine. Differences include formulation, dosing schedule, FDA indications, and pharmacokinetics. Oral azacitidine results in lower blood levels than IV azacitidine but can be administered over longer periods (14 days versus 5–7 days per 28-day cycle). Onureg is specifically approved for maintenance therapy in remission, not for treating active AML.

What are the latest research and future developments surrounding Onureg?

There is growing interest in oral azacitidine because it improves quality of life by avoiding injections or IV therapy. Research is exploring its use in combination with other agents such as venetoclax, in myelodysplastic syndrome, after allogeneic transplant, or in relapse settings with combination pill therapies. The goal is to expand oral therapy options and improve patient convenience while maintaining effectiveness. Onureg is currently the first FDA-approved maintenance therapy in AML.