ONUREG

What it is

ONUREG contains azacitidine, with vials containing 100 mg of azacitidine. ONUREG is also available as a film-coated tablet in 200 mg and 300 mg strengths. The finished product is supplied in a sterile form for reconstitution as a suspension for subcutaneous injection or reconstitution as a solution with further dilution for intravenous infusion.

Approved indications ONUREG is indicated for the treatment of patients with:

— Intermediate-2 and High-risk Myelodysplastic Syndromes (MDS) according to the International Prognostic Scoring System (IPSS) — Chronic Myelomonocytic Leukaemia (CMML) (10–29% marrow blasts without Myeloproliferative Disorder) — Acute Myeloid Leukaemia (AML) with 20–30% blasts and multi-lineage dysplasia, according to World Health Organisation Classification, in whom allogeneic stem cell transplantation is not indicated

Dosing overview

The recommended starting dose for the first treatment cycle, for all patients regardless of baseline haematology laboratory values, is 75 mg/m² of body surface area given subcutaneously or by intravenous infusion, daily for seven days, followed by a rest period of 21 days (28-day treatment cycle). Cycles should be repeated every 28 days, and it is recommended that patients be treated for a minimum of 6 cycles, although complete or partial response may require more than 6 treatment cycles. Patients should be monitored for haematological response and renal toxicities, and a dose delay or reduction may be necessary.

Key safety warnings

Treatment with ONUREG is associated with anaemia, neutropenia and thrombocytopenia, particularly during the first 2 cycles. Complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle. Patients with a history of severe congestive heart failure, clinically unstable cardiac disease or pulmonary disease were excluded from the pivotal clinical study and therefore the safety and efficacy of ONUREG in these patients has not been established. Cases of differentiation syndrome (also known as retinoic acid syndrome) have been reported in patients receiving ONUREG. Differentiation syndrome may be fatal, and symptoms and clinical findings include respiratory distress, pulmonary infiltrates, fever, rash, pulmonary oedema, peripheral oedema, rapid weight gain, pleural effusions, pericardial effusions, hypotension and renal dysfunction. Treatment with high-dose IV corticosteroids and haemodynamic monitoring should be considered at first onset of symptoms or signs suggestive of differentiation syndrome. Patients with extensive tumour burden due to metastatic disease have been rarely reported to experience progressive hepatic coma and death during ONUREG treatment, especially in such patients with baseline serum albumin < 30 g/l. ONUREG is contraindicated in patients with advanced malignant hepatic tumours. Since azacitidine and/or its metabolites are primarily excreted by the kidneys, patients with mild or moderate renal impairment should be monitored closely and the dose adjusted based on haematology and renal laboratory values.

Contraindications

ONUREG is contraindicated in the following: patients with known hypersensitivity to azacitidine or to any of the excipients; patients with advanced malignant hepatic tumours; pregnancy; patients with severe renal impairment (creatinine clearance < 30 mL/s/min).

PBS listing

The 200 mg tablet is listed on the PBS as 1 item with authority required restriction, at an ex-manufacturer price of A$6613.88. The 300 mg tablet is listed on the PBS as 2 items with authority required restriction, at an ex-manufacturer price of A$6613.88.

Regulatory history

ONUREG (azacitidine powder for injection) was first approved on the ARTG on 23 July 2019. The 200 mg and 300 mg film-coated tablet formulations were first listed on the ARTG on 8 April 2022.