Manufacturer:

Human Genome Sciences and GlaxoSmithKline

Pharmacological Class:

Biologic (human IgG1gamma monoclonal antibody).

Active Ingredient(s):

Belimumab120mg/vial, 400mg/vial; pwd for IV infusion after recon­stitution and dilution.

Indication(s):

Systemic lupus erythematosus, in adults with active, autoantibody-positive SLE on standard therapy.

Pharmacology:

Belimumab is a human IgG1gamma monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS), a B cell survivor factor. It blocks the binding of soluble BLyS to its ­receptors on B cells, thus inhibiting the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

Clinical Trials:

Three randomized, placebo-­controlled studies involving 2133 patients with active, autoantibody positive SLE evaluated the safety and efficacy of belimumab. The patients were on a stable standard of care regimen (eg, corticosteroids, antimalarials, NSAIDs, and immunosuppressives); those with severe active lupus nephritis or severe active CNS lupus were excluded, as was the use of other biologics and IV cyclophosphamide.

In Trial 1, wherein several doses of belimu­mab were compared with placebo over 52 weeks, belimumab offered a benefit for patients with autoantibody-positive disease.

Trials 2 and 3 involved patients with active SLE and positive autoantibody tests at baseline. In both studies, more than half of the subjects had three or more organ systems with active disease at baseline. Patients were stratified by disease severity (measured by SELENA-SLEDAI scores), proteinuria level, and race. They were then randomized to receive either belimumab 1mg/kg, 10mg/kg, or placebo. The study drug was given by IV infusion on Days 0, 14, 28, and then every 28 days for 48 or 72 weeks in Trials 3 and 2, respectively, in addition to standard care.

The primary efficacy endpoint in both studies was the response rate at week 52 according to the SLE Responder Index (SRI), a composite endpoint that took into account the disease severity score, an organ domain score (which reflected significant worsening in any specific organ system), and a physician’s global assessment score.

In each trial, the proportion of patients achieving response was significantly higher in the belimumab 10mg/kg group than in the placebo group. At Week 76, the response rate with the 10mg/kg dose was not significantly different than placebo. The reductions in disease severity, as reflected in the SRI, were improvements in the most commonly involved organ systems (eg, mucocutaneous, musculoskeletal, and immunology).

Legal Classification:

Rx

Adults:

Give by IV infusion over 1 hour; slower if infusion reaction occurs. 10mg/kg every 2 weeks for 3 doses, then 10mg/kg every 4 weeks. May premedicate for infusion/hypersensitivity reactions (eg, APAP, diphenhydramine).

Children:

Not recommended.

Warnings/Precautions:

Severe active lupus nephritis or CNS lupus: not recommended. More deaths reported with Benlysta than ­placebo in clinical trials. Supervise infusion; have resuscitative equipment and trained personnel available in case of infusion/hypersensitivity ­reactions. Chronic infections: do not start ­therapy; if initiated, consider suspending if new infections develop and monitor closely. Monitor for malignancies, depression or other mood changes. Elderly. Black/African American. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interaction(s):

Immunizations (may get sub­optimal response); avoid live vaccines for 30 days prior to and during treatment. Concomitant other biologicals or IV cyclophosphamide: not recommended.

Adverse Reaction(s):

Infections (eg, URI, UTI, nasopharyngitis, sinusitis, bronchitis, influenza; may be serious/fatal), psychological effects (eg, depression, insomnia, anxiety, suicide), GI upset, fever, migraine, extremity pain, ­infusion and/or hypersensitivity reactions.

How Supplied:

Single-use vials (120mg in 5mL, 400mg in 20mL)—1

Last Updated:

3/31/2011