ONIVYDE

What it is

ONIVYDE is a topoisomerase 1 inhibitor (irinotecan) encapsulated in lipid bilayer vesicles or liposomes, presented in solution as a liposomal dispersion for intravenous use. The liposome is a small unilamellar lipid bilayer vesicle, approximately 110 nm in diameter, which encapsulates an aqueous space containing irinotecan in a gelated or precipitated state, as the sucrosofate (sucrose octasulfate) salt. Each 10 mL vial contains 43 mg irinotecan equivalent to 50 mg irinotecan hydrochloride trihydrate. ONIVYDE is not equivalent to non-liposomal irinotecan hydrochloride and they should not be interchanged.

Approved indications —

In combination with oxaliplatin and 5-fluorouracil (5-FU) and leucovorin (LV) for the first-line treatment of metastatic pancreatic adenocarcinoma. — In combination with 5-FU and LV for the treatment of metastatic pancreatic adenocarcinoma after disease progression following gemcitabine-based therapy.

Dosing overview

For first-line treatment, the recommended dose of ONIVYDE is 50 mg/m² intravenously over 90 minutes, followed by oxaliplatin 60 mg/m² intravenously over 120 minutes, followed by LV 400 mg/m² intravenously over 30 minutes, followed by 5-FU 2,400 mg/m² intravenously over 46 hours, administered every 2 weeks until development of disease progression or unacceptable toxicity. For treatment after prior gemcitabine-based therapy, the recommended dose of ONIVYDE is 70 mg/m² intravenously over 90 minutes, followed by LV 400 mg/m² intravenously over 30 minutes, followed by 5-FU 2,400 mg/m² intravenously over 46 hours, administered every 2 weeks until development of disease progression or unacceptable toxicity. For patients known to be homozygous for the UGT1A1*28 allele, consider a reduced ONIVYDE starting dose of 50 mg/m², with an increase to 70 mg/m² as tolerated in subsequent cycles.

Key safety warnings

Myelosuppression with severe neutropenia is very common with ONIVYDE treatment, and life-threatening neutropenic sepsis can occur. In NAPOLI 3, Grade 3 and 4 neutropenia occurred in 26% of patients receiving ONIVYDE in combination with oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX) and fatal neutropenic sepsis occurred in 0.3% of patients. Assess full blood cell counts on Days 1 and 8 of every cycle and more frequently if clinically indicated. Severe diarrhoea is very common with ONIVYDE treatment, and can have life-threatening sequelae such as dehydration, electrolyte imbalances, renal toxicity, inflammation and infection. In NAPOLI 3, Grade 3 and 4 diarrhoea (early or late-onset) occurred in 20% of patients receiving ONIVYDE (as part of the NALIRIFOX regimen). In NAPOLI-1, Grade 3 or 4 diarrhoea occurred in 13% of patients receiving ONIVYDE (in combination with 5-FU/LV). Withhold ONIVYDE for all Grade ≥ 2 diarrhoea. ONIVYDE can cause acute infusion reactions (including rash, urticaria, periorbital oedema or pruritus), and anaphylactic/anaphylactoid reactions and angioedema may occur. Non-liposomal irinotecan (hydrochloride) can cause severe or fatal interstitial lung disease (ILD)/pneumonitis. Pneumonitis was reported in 0.3% of patients receiving ONIVYDE in combination with oxaliplatin and 5-FU/LV (NALIRIFOX) in NAPOLI-3. ONIVYDE has been associated with thromboembolic events such as pulmonary embolism, venous thrombosis and arterial thromboembolism.

Contraindications

ONIVYDE is contraindicated in patients with hypersensitivity to irinotecan or to any of the excipients.

PBS listing

ONIVYDE is not currently listed on the Pharmaceutical Benefits Scheme. In November 2024, the PBAC recommended against listing for metastatic pancreatic adenocarcinoma (first-line treatment in combination with oxaliplatin, 5-fluorouracil and folinic acid), noting that the resubmission did not address previous concerns, that the comparator (FOLFIRINOX) and economic analysis approach were inappropriate, and that clinical claims of superior effectiveness and safety were not supported.

Regulatory history

ONIVYDE (irinotecan as sucrosofate) 43 mg/10 mL nanoliposomal concentrated injection for infusion was first listed on the ARTG on 2016-12-19.