ALPROLIX

What it is

ALPROLIX is a long-acting, fully recombinant, fusion protein comprising human coagulation factor IX (FIX) covalently linked to the Fc domain of human IgG1, and produced by recombinant DNA technology. Eftrenonacog alfa is produced by recombinant DNA technology in a human embryonic kidney (HEK) cell line, which has been extensively characterised. ALPROLIX is formulated as a sterile, preservative-free, non-pyrogenic, lyophilised, white to off-white powder to cake, for intravenous (IV) administration in a single-use vial. Each single-use vial contains nominally 250, 500, 1000, 2000, 3000 or 4000 International Units (IU) of eftrenonacog alfa.

Approved indications

ALPROLIX is a long-acting anti-haemophilic factor (recombinant) indicated in adults and children with haemophilia B (congenital factor IX deficiency) for: — Control and prevention of bleeding episodes — Routine prophylaxis to prevent or reduce the frequency of bleeding episodes — Perioperative management (surgical prophylaxis)

Dosing overview

1 IU of ALPROLIX per kg body weight is expected to increase the circulating level of factor IX by approximately 1% [IU/dL] in patients 12 years of age or older. The recommended starting regimens for routine prophylaxis are either: 50 IU/kg once weekly or 100 IU/kg once every 10 days. Either regimen may be adjusted based on patient response. Higher doses or more frequent dosing may be needed in patients less than 12 years of age.

Key safety warnings

Allergic type hypersensitivity reactions, including anaphylaxis, have been reported with ALPROLIX. The presence of inhibitors has been associated with allergic reactions with factor IX replacement therapies, including with ALPROLIX. Patients should be advised to discontinue use of ALPROLIX if hypersensitivity symptoms occur and contact a physician and/or seek immediate emergency care. Thrombotic events with other factor IX products have been reported including in patients receiving continuous-infusion through a central venous catheter. The safety and efficacy of ALPROLIX administration by continuous infusion have not been established. Inhibitors have been reported with factor replacement therapy in the treatment of haemophilia B. Patients using ALPROLIX should be monitored for the development of factor IX inhibitors by appropriate clinical observations and laboratory tests. Inhibitors have been reported with ALPROLIX in the treatment of haemophilia B, including in previously untreated patients. Patients with factor IX inhibitors may be at an increased risk of anaphylaxis upon subsequent challenge with factor IX. Nephrotic syndrome has been reported following immune tolerance induction with factor IX products in haemophilia B patients with factor IX inhibitors and a history of allergic reactions to factor IX. The safety and efficacy of using ALPROLIX for immune tolerance induction have not been established.

Contraindications

ALPROLIX is contraindicated in patients who have manifested severe hypersensitivity reactions, including anaphylaxis, to the product or its components.

PBS listing

Information regarding PBS listing is not available in the provided source documents.

Regulatory history

ALPROLIX eftrenonacog alfa was first registered on the ARTG on 1 May 2014, initially in five strengths (250 IU, 500 IU, 1000 IU, 2000 IU, and 3000 IU). A 4000 IU strength was added to the ARTG on 16 January 2020. The TGA approved the registration of ALPROLIX, a new biological entity, for the treatment of haemophilia B on 17 April 2014. Clinical studies demonstrated that ALPROLIX was effective in the control and prevention of bleeding episodes, routine prophylaxis, and perioperative management in adults and adolescents with haemophilia B. The safety profile was acceptable, with no new safety concerns identified during the evaluation.