BENLYSTA

What it is

Belimumab is a human IgG1 monoclonal antibody specific for soluble human B Lymphocyte Stimulator protein (BLyS). Belimumab is produced by recombinant DNA technology in a mammalian cell expression system. BENLYSTA is subject to additional monitoring in Australia. This will allow quick identification of new safety information.

Approved indications

— Add-on therapy for reducing disease activity in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity (for example, ANA titre ≥ 1:80 and/or anti-dsDNA titre ≥30 IU/mL) despite standard therapy. — Treatment of active lupus nephritis in adult patients who are receiving standard therapy.

Dosing overview

BENLYSTA treatment should be initiated and supervised by a healthcare professional experienced in the diagnosis and treatment of SLE. BENLYSTA infusions should be administered in an environment where full resuscitation facilities are available, and under the close supervision of an experienced healthcare professional. BENLYSTA should be infused over a 1-hour period. BENLYSTA must not be administered as an intravenous push or bolus. Discontinuation of treatment with BENLYSTA should be considered if there is no improvement in disease control after 6 months of treatment.

Key safety warnings

Administration of BENLYSTA may result in infusion or injection-related systemic and hypersensitivity reactions, which can be severe or fatal. In the event of a severe reaction, BENLYSTA administration must be interrupted and appropriate medical therapy administered. In clinical trials, serious infusion and hypersensitivity reactions affected less than 1% of patients, and included anaphylactic reaction, bradycardia, hypotension, angioedema, and dyspnoea. Infusion or injection-related systemic and hypersensitivity reactions occurred more frequently with the first two doses and tended to decrease with subsequent doses. Severe infections, including fatal cases, have been reported in SLE patients receiving immunosuppressant therapy, including BENLYSTA. The mechanism of action of BENLYSTA may increase the risk for the development of serious and fatal infections. In controlled clinical studies, fatal infections such as pneumonia and sepsis were found to occur more frequently in patients receiving belimumab compared with placebo, while the incidence of serious infections was similar across the belimumab and placebo groups. Progressive multifocal leukoencephalopathy (PML) resulting in neurological deficits, including fatal cases, has been reported in SLE patients receiving immunosuppressant pharmacotherapy, including BENLYSTA. A diagnosis of PML should be considered in any patient presenting with new-onset or deteriorating neurological signs and symptoms. The patient should be referred to a neurologist or other appropriate specialist for evaluation as clinically indicated. In controlled clinical intravenous and subcutaneous studies, psychiatric disorders (depression, suicidal ideation and behaviour) have been reported more frequently in patients receiving BENLYSTA. Physicians should carefully assess the risk of depression and suicide considering the patient's medical history and current psychiatric status before treatment with belimumab, and continue to monitor patients during treatment. There were more deaths reported with BENLYSTA than with placebo during the controlled period of the intravenous clinical trials. Out of 2133 patients in 3 clinical trials, a total of 14 deaths occurred during the placebo-controlled, double-blind treatment periods: 3/675 (0.4%), 5/673 (0.7%), 0/111 (0%), and 6/674 (0.9%) deaths in the placebo, BENLYSTA 1 mg/kg, BENLYSTA 4 mg/kg, and BENLYSTA 10 mg/kg groups, respectively.

Contraindications

BENLYSTA is contraindicated in patients who have demonstrated anaphylaxis to belimumab or to any of the excipients.

Regulatory history

BENLYSTA (belimumab) was first listed on the ARTG on 2012-10-18 for the 120 mg and 400 mg powder for injection vials (licence category RE). The AusPAR approval date was 2012-07-06. Benlysta was approved as add-on therapy for reducing disease activity in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity (ANA titre ≥ 1:80 and/or anti-dsDNA titre ≥30 IU/mL) despite standard therapy. The subcutaneous formulation in pre-filled syringe and pre-filled pen (200 mg/mL) was first listed on 2019-11-27.