infant deaths is not known. The relevance of these findings to humans is not known. Other treatment-related findings were limited to the expected reversible reduction of B cells in both dams and infants and reversible reduction of IgM in infant monkeys. B-cell numbers recovered after the cessation of belimumab treatment by about 1 year post-partum in adult monkeys and by 3 months of age in infant monkeys. IgM levels in infants exposed to belimumab in utero recovered by 6 months of age.
Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to BENLYSTA, a pregnancy registry has been established. Healthcare professionals are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-681-6296.
8.3 Nursing MothersIt is not known whether BENLYSTA is excreted in human milk or absorbed systemically after ingestion. However, belimumab was excreted into the milk of cynomolgus monkeys. Because maternal antibodies are excreted in human breast milk, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of breastfeeding to the infant and the importance of the drug to the mother.
8.4 Pediatric UseSafety and effectiveness of BENLYSTA have not been established in children.
8.5 Geriatric UseClinical studies of BENLYSTA did not include sufficient numbers of subjects aged 65 or over to determine whether they respond differently from younger subjects. Use with caution in elderly patients.
8.6 Race advertisementIn Trial 2 and Trial 3, response rates for the primary endpoint were lower for black subjects in the BENLYSTA group relative to black subjects in the placebo group [see Clinical Studies (14)]. Use with caution in black/African-American patients.
10 OVERDOSAGEThere is no clinical experience with overdosage of BENLYSTA. Two doses of up to 20 mg/kg have been given by intravenous infusion to humans with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg.
11 DESCRIPTIONBENLYSTA (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 mammalian cell expression system.
BENLYSTA is supplied as a sterile, white to off-white, preservative-free, lyophilized powder for intravenous infusion. Upon reconstitution with Sterile Water for Injection, USP, [see Dosage and Administration (2.3)] each single-use vial delivers 80 mg/mL belimumab in 0.16 mg/mL citric acid, 0.4 mg/mL polysorbate 80, 2.7 mg/mL sodium citrate, and 80 mg/mL sucrose, with a pH of 6.5.
12 CLINICAL PHARMACOLOGY12.1 Mechanism of ActionBENLYSTA is a BLyS-specific inhibitor that blocks the binding of soluble BLyS, a B-cell survival factor, to its receptors on B cells. BENLYSTA does not bind B cells directly, but by binding BLyS, BENLYSTA inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.
12.2 PharmacodynamicsIn Trial 1 and Trial 2 in which B cells were measured, treatment with BENLYSTA significantly reduced circulating CD19+, CD20+, naïve, and activated B cells, plasmacytoid cells, and the SLE B-cell subset at Week 52. Reductions in naïve and the SLE B-cell subset were observed as early |
