JIVI

What it is

JIVI is a pegylated B-domain deleted recombinant human coagulation factor VIII (PEG-BDD-rFVIII), presented as a sterile, stable, purified dried concentrate available in vials of 250, 500, 1000, 2000 or 3000 IU. The active substance, damoctocog alfa pegol, is produced in baby hamster kidney cells with a 60 kDa branched polyethylene-glycol moiety. JIVI is produced without the addition of any human or animal derived protein in the cell culture process, purification, PEGylation or final formulation.

Approved indications

JIVI is indicated for use in previously treated adults and adolescents (12 years of age and older) with haemophilia A for: — Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes — On-demand treatment and control of bleeding episodes — Per-operative management of bleeding (surgical prophylaxis) JIVI does not contain von Willebrand factor, and therefore is not indicated in patients with von Willebrand's disease.

Dosing overview

The recommended initial prophylactic dose is 30–40 IU/kg twice weekly, which may be adjusted to 45–60 IU/kg every 5 days based on the patient's bleeding frequency. JIVI can also be individually adjusted to less frequent dosing, such as 60 IU/kg every 7 days. For overweight patients, the maximum dose per injection for prophylaxis should not be higher than approximately 6000 IU. For on-demand treatment and surgical procedures, doses depend on the degree of haemorrhage or type of procedure, ranging from factor VIII levels of 20–40% for early haemarthrosis or muscle bleeding, to 80–100% for major surgery, with dosing intervals varying from every 24–48 hours to every 8–24 hours based on clinical circumstances.

Key safety warnings

Allergic type hypersensitivity reactions are possible with JIVI. The medicinal product may contain traces of mouse and hamster proteins, and hypersensitivity reactions could also be related to antibodies against PEG. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the management of individuals with haemophilia A. The risk of developing inhibitors is correlated to the severity of the disease and the exposure to factor VIII, with risk being highest within the first 50 exposure days but continuing throughout life. A clinical immune response associated with anti-PEG antibodies, manifested as symptoms of acute hypersensitivity and/or loss of drug effect, has been observed primarily within the first 4 exposure days. Low post-injection factor VIII levels in the absence of detectable factor VIII inhibitors indicate that loss of drug effect is likely due to anti-PEG antibodies; in such cases JIVI should be discontinued and patients switched to a previously effective factor VIII product. In completed clinical studies with paediatric patients less than 12 years of age, adverse reactions due to immune response to PEG were observed in children less than 6 years of age. In 23% of patients in the age group less than 6 years, loss of drug effect due to neutralising anti-PEG IgM antibodies during the first 4 exposure days was observed. In 7% of these patients, loss of drug effect was combined with hypersensitivity reactions. In patients with existing cardiovascular risk factors, substitution therapy with factor VIII may increase the cardiovascular risk.

Contraindications

JIVI is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, and in patients with known allergic reactions to mouse or hamster proteins.

Regulatory history

JIVI damoctocog alfa pegol was first listed on the ARTG on 27 March 2023 in five strengths: 250 IU, 500 IU, 1000 IU, 2000 IU, and 3000 IU. The product was approved by the TGA on 21 March 2023 for routine prophylactic treatment, on-demand treatment, and per-operative management of bleeding episodes in previously treated adults and adolescents (12 years and older) with haemophilia A. The TGA found no quality or nonclinical objections to the approval of JIVI. The product is a longer-acting recombinant factor VIII, with PEGylation increasing its half-life, designed for both prophylaxis and on-demand treatment of haemophilia A.