What are the features of Belimumab (Benlysta)?

From the Guidelines

Belimumab is a monoclonal antibody medication that has been shown to be effective in treating systemic lupus erythematosus (SLE), particularly in patients with active, autoantibody-positive disease who have not responded adequately to standard therapies, as demonstrated in a recent systematic literature review informing the 2023 update of the EULAR recommendations 1.

Key Features of Belimumab

• Mechanism: B-lymphocyte stimulator (BLyS) inhibitor, reducing abnormal B cell activity and autoantibody production central to lupus pathogenesis
• Formulations: Intravenous (10 mg/kg every 2 weeks for the first three doses, then every 4 weeks thereafter) and subcutaneous (200 mg once weekly self-injection)
• Target population: Active, autoantibody-positive SLE patients who have not responded adequately to standard therapies
• Approved indications: SLE and lupus nephritis
• Common side effects: Infusion reactions, infections, headache, nausea, and fatigue
• Contraindications and precautions: Should not be administered with live vaccines, requires monitoring for infections and depression

Efficacy and Safety

• Clinical improvement typically observed after 3-6 months of consistent therapy
• Used as add-on therapy to standard lupus treatments rather than as monotherapy
• Recent phase III RCTs, such as the EMBRACE and BLISS-NEA studies, have demonstrated the efficacy of belimumab in specific ethnic/racial populations, with SLE Responder Index (SRI)-4 responses at 52 weeks being higher with belimumab versus placebo 1
• Safety issues, such as serious depression and treatment-emergent suicidality, have been reported in some studies, but overall incidence of adverse events and mortality is similar between belimumab and placebo 1

From the FDA Drug Label

Belimumab is a human IgG1λ monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS, also referred to as BAFF and TNFSF13B). Belimumab has a molecular weight of approximately 147 kDa. Belimumab is produced by recombinant DNA technology in a murine cell (NS0) expression system BENLYSTA (belimumab) for injection is a sterile, white to off-white, preservative‑free, lyophilized powder in a single-dose vial for reconstitution and dilution prior to intravenous infusion. BENLYSTA for injection is supplied as 120 mg per vial and 400 mg per vial and requires reconstitution with Sterile Water for Injection, USP (1.5 mL and 4. 8 mL, respectively) to obtain a concentration of 80 mg/mL BENLYSTA (belimumab) injection is a sterile, preservative-free, clear to opalescent, and colorless to pale yellow solution for subcutaneous use It is supplied in a 1-mL single-dose prefilled autoinjector with a fixed 27-gauge, half-inch needle or in a 1-mL single-dose prefilled syringe with a fixed 27-gauge, half-inch needle with a needle guard.

The main features of belimumab are:

• Monoclonal antibody: specific for soluble human B lymphocyte stimulator protein (BLyS)
• Molecular weight: approximately 147 kDa
• Production method: recombinant DNA technology in a murine cell (NS0) expression system
• Formulations:
  • Intravenous infusion: lyophilized powder in a single-dose vial for reconstitution and dilution
  • Subcutaneous injection: prefilled autoinjector or prefilled syringe with a fixed 27-gauge, half-inch needle
• Supplied doses: 120 mg per vial and 400 mg per vial for intravenous infusion, and 200 mg per 1 mL for subcutaneous injection 2 2

From the Research

Features of Belimumab

• Belimumab is a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator (BLyS) 3, 4.
• It is a human immunoglobulin G1λ monoclonal antibody that inhibits the binding of soluble B lymphocyte stimulator to B cells 5.
• Belimumab has been shown to reduce autoantibody levels in people with systemic lupus erythematosus (SLE) and help control disease activity 6.
• It is approved as add-on therapy in adult patients with active, autoantibody-positive SLE despite standard therapy 5.

Mechanism of Action

• Belimumab binds to soluble BAFF and inhibits it from binding to its receptors, which are involved in the survival and differentiation of B cells 4.
• By inhibiting BLyS, belimumab reduces the selection and survival of B cells, which are thought to contribute to the pathogenesis of autoimmune diseases such as SLE 3.

Clinical Efficacy

• Belimumab has been shown to be effective in reducing overall disease activity and reducing the incidence and severity of flares in patients with SLE 5.
• It has also demonstrated steroid-sparing effects and was associated with clinically meaningful improvements in health-related quality of life and fatigue 5.
• In phase III trials, treatment with IV or SC belimumab plus standard therapy was effective in terms of reducing overall disease activity and reducing the incidence and severity of flares 5.

Safety and Tolerability

• Belimumab was generally well tolerated in clinical trials, with low rates of immunogenicity 5.
• The proportion of participants experiencing harm may not differ meaningfully between the belimumab and placebo groups, although evidence related to harms is inconclusive and mostly of moderate to low-certainty evidence 6.