Targeted mechanism of action

See how BENLYSTA works.

BENLYSTA is the only FDA-approved treatment designed to target BLyS/BAFF, an underlying cause of lupus and lupus nephritis1,2

video transcript

NARRATOR:
BENLYSTA (belimumab) is designed for lupus. BENLYSTA is the only biologic with a mechanism of action that selectively targets the B-lymphocyte stimulator protein, or BLyS, a known underlying cause of systemic lupus erythematosus, or SLE, with or without lupus nephritis.

ON-SCREEN TEXT:
BENLYSTA (belimumab)
BLyS

REFERENCES: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021. 2. Neusser MA, Lindenmeyer MT, Edenhofer I, et al. Intrarenal production of B-cell survival factors in human lupus nephritis. Mod Pathol. 2011;24(1):98-107. 3. Stohl W, Hilbert DM. The discovery and development of belimumab: the anti-BLyS–lupus connection. Nat Biotechnol. 2012;30(1):69-77. 4. Suso JP, Posso-Osorio I, Jiménez CA, et al. Profile of BAFF and its receptors’ expression in lupus nephritis is associated with pathological classes. Lupus. 2018;27(5):708-715.

NARRATOR:
BENLYSTA selectively blocks the binding of soluble BLyS to its receptor on B cells.

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B cell
B-cell membrane
BAFF-R
BAFF-R: B-cell activating factor receptor

REFERENCES: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021. 2. Kim HM, Yu KS, Lee ME, et al. Crystal structure of the BAFF–BAFF-R complex and its implications for receptor activation. Nat Struct Mol Biol. 2003;10(5):342-348. 3. Shin W, Lee HT, Lim H, et al. BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus. Nat Comm. 2018;9(1):1-11.

NARRATOR:
Although it does not bind to B cells directly, BENLYSTA inhibits the survival of autoreactive B cells and reduces the differentiation of B cells into immunoglobulin-producing plasma cells. The clinical relevance of these effects on B cells has not been established.

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The clinical relevance of these effects on B cells has not been established.
B cell
Plasma cell
Hypothetical patient.

REFERENCE: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021.

NARRATOR:
In patients with lupus who were positive for anti-double-stranded DNA, treatment with BENLYSTA resulted in a 41% reduction in anti-double-stranded DNA antibody levels over 52 weeks. Reductions were also seen in IgG CD19 positive, CD20 positive, naïve B cells, activated B cells, and the SLE B-cell subset at Week 52. Additionally increases in complement proteins C3 and C4 were also observed at Week 52 in patients with low complement levels at baseline.

ON-SCREEN TEXT:
Overview of Pharmacodynamics for BENLYSTA
Hypothetical patient.
BENLYSTA resulted in a 41% reduction in anti-double-stranded DNA antibody levels over 52 weeks.
The clinical relevance of these results has not been fully established.
Reductions in: IgG, CD19+ B cells, CD20+ B cells, naïve B cells, activated B cells, B-cell subset
At Week 52
Increases in complement proteins C3 & C4 at Week 52

REFERENCES: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021. 2. Stohl W, Hiepe F, Latinis KM, et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64(7):2328-2337.

NARRATOR:
In patients with lupus nephritis, treatment with BENLYSTA led to a decrease in serum IgG as early as Week 4, and, subsequently, there was an increase in serum IgG levels, which was associated with decreased proteinuria. Reductions in autoantibodies, total circulating B cells, and B-cell subsets and increases in complement proteins were consistent with what was observed in SLE trials.

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Nephrons
IgG
Reductions in autoantibodies
Reductions in B cells
Increase in complement
The clinical relevance of these results has not been fully established.

REFERENCES: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021. 2. Crow MK. Etiology and pathogenesis of systemic lupus erythematosus. Kelley and Firestein's Textbook of Rheumatology. Elsevier; 2017;1329-1344. 3. Marieb EN, Hoehn K, eds. Human Anatomy & Physiology. 11th ed. Pearson Education, Inc; 2019. 4. Davidson A, Berthier C, Kretzler M. Pathogenetic mechanisms in lupus nephritis. In: Dubois' Lupus Erythematosus and Related Syndromes. WB Saunders; 2013: 237-255.

NARRATOR:
BENLYSTA. An FDA-approved treatment option for patients with lupus or lupus nephritis.

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Benlysta (belimumab) Intravenous Use 120 mg/vial Subcutaneous Use 200 mg/mL
©2022 GSK or licensor.
BELVID220007 April 2022
Produced in USA.
Trademarks owned by or licensed to the GSK group of companies.

REFERENCE: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021.

Image: Mechanism of action for BENLYSTA
Image: Mechanism of action for BENLYSTA

The clinical relevance of these results has not been definitively established.

* BENLYSTA does not directly bind to B cells or directly deplete B-cell population.3,4

BAFF = B-cell activating factor; BLyS = B-lymphocyte stimulator protein.

BLyS/BAFF is elevated in patients with lupus5

Icon: BLyS levels

BLyS/BAFF levels correlate with lupus disease activity and anti-dsDNA titers in many patients1,6

The clinical relevance of these results has not been definitively established.

Anti-dsDNA = anti-double–stranded DNA; BAFF = B-cell activating factor; BLyS = B-lymphocyte stimulator protein.

   

Improvement in key serological markers was seen as early as Week 8

At Week 52, adult patients with lupus on BENLYSTA showed:

Icon: Down arrow

Reductions in:

  • IgG
  • Anti-dsDNA antibodies*
Icon: Up arrow

Increases in:

  • Complement (C3 and C4)†

Adult patients with lupus on BENLYSTA experienced a

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41% reduction in anti-dsDNA levels over 52 weeks5

See the data

The clinical relevance of these results has not been definitively established.

* In patients who were positive for anti-dsDNA ≥30 IU/mL.

† In patients with low complement levels at baseline.

Anti-dsDNA = anti-double–stranded DNA; IgG = immunoglobulin G.

Icon: B cells

Reductions in B-cell populations5,7

At Week 52, adult patients with lupus on BENLYSTA had significant reductions in B-cell subsets

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Median change from baseline to Week 52

  BENLYSTA IV 10 mg/kg + ST Placebo + ST
  Baseline Week 52 Baseline Week 52
CD19+ B cells 94.50
(n=260)		 -48.45
(n=193)		 93.00
(n=262)		 -10.42
(n=189)
CD20+ B cells 94.00
(n=251)		 -37.00
(n=173)		 92.00
(n=249)		 -4.00
(n=172)
Naïve B cells 74.00
(n=251)		 -44.00
(n=173)		 79.00
(n=249)		 -3.00
(n=172)
Activated B cells 2285.00
(n=247)		 -827.00
(n=173)		 2044.00
(n=247)		 -337.00
(n=171)
Lupus B-cell subset 377.00
(n=251)		 -77.50
(n=176)		 293.00
(n=249)		 17.00
(n=173)

Data from the BLISS-76 study only. The clinical relevance of these results has not been definitively established.

BENLYSTA reduced autoantibodies and normalized low complement levels5

Median change in biomarkers over time

Pooled data from BLISS-52 and BLISS-76

Median change in biomarkers over time charts
Median change in biomarkers over time charts
Median change in biomarkers over time charts
Median change in biomarkers over time charts

The clinical relevance of these results has not been definitively established.

Used with permission from Stohl W, et al. Arthritis Rheum. 2012;64(7):2328-2337. ©2012 John Wiley and Sons.

* In patients who were positive for anti-dsDNA ≥30 IU/mL.

† In patients with low complement levels at baseline.

Anti-dsDNA = anti-double–stranded DNA; IV = intravenous; ST = standard therapy.

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