Precision Anti-Inflammatory Therapy: AbbVie’s Novel ADC ABBV-3373 Featured in Science Translational Medicine

Mar 22, 2024 07:30 CST Updated 07:30

AbbVie

Innovative Drug Developer

▎Edited by the WuXi AppTec content team

Glucocorticoids are effective drugs for treating various inflammatory diseases, but due to their often systemic effects, patients may experience serious side effects such as fractures, elevated blood sugar, and glaucoma if the treatment duration is too long. Therefore, the dosage and duration of glucocorticoid therapy are restricted. If it were possible to selectively target inflamed tissues, the clinical application of glucocorticoids would be greatly enhanced.

In a study published in *Science Translational Medicine*, the research team at AbbVie Bioresearch Center designed aAn antibody-drug conjugate named ABBV-3373, solve this problem.

ABBV-3373 conjugates an anti-tumor necrosis factor (TNF) antibody with a compound that enhances glucocorticoid receptor activity, where TNF is a protein active on the surface of immune cells. This design allows the conjugate to be taken up by cells.It will bind to TNF on overactive immune cells and release glucocorticoid receptor modulators to quell the inflammatory activity of the cells.

▲Structure and Characteristics of ABBV-3373(Image source: Reference [1])

In mouse experiments, ABBV-3373 effectively inhibited inflammatory signaling in mice with contact hypersensitivity or induced arthritis, and a single dose completely suppressed arthritis for more than 30 days.

In addition, the Phase 1 clinical trial in healthy volunteers confirmed the pharmacokinetic profile of ABBV-3373 without significantly affecting systemic markers of glucocorticoids in the volunteers.This outcome paves the way for overcoming the major safety hurdle in the clinical use of glucocorticoids, supporting their potential as a safer and more sustainable anti-inflammatory tool.

References:

[1] McPherson et al. An anti–TNF–glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases. Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.add8936

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