What is the comparison of binding affinity to receptors between lebrikizumab (Anti-IL-13 monoclonal antibody) and tralokinumab (Anti-IL-13 monoclonal antibody)?

From the Guidelines

Lebrikizumab has a higher binding affinity to IL-13 compared to tralokinumab, with approximately 10-fold higher affinity, allowing for more effective neutralization of IL-13 in the treatment of atopic dermatitis. The binding affinity of lebrikizumab to IL-13 is significantly higher than that of tralokinumab, with a dissociation constant (KD) of about 10 pM for lebrikizumab versus approximately 100 pM for tralokinumab 1. This difference in binding affinity is due to their distinct antibody structures and epitope targeting, despite both being monoclonal antibodies directed against IL-13. Some key points to consider when comparing lebrikizumab and tralokinumab include:

• Lebrikizumab specifically targets the IL-13Rα1 binding site on IL-13, preventing receptor heterodimerization, while tralokinumab binds to a different epitope on IL-13 1.
• The higher binding affinity of lebrikizumab may contribute to its clinical efficacy in treating atopic dermatitis, although head-to-head clinical trials comparing these two medications are limited.
• Tralokinumab, a monoclonal antibody targeting interleukin-13, has been shown to significantly improve the signs and symptoms of AD as well as QOL in multiple clinical trials 1. However, the difference in binding characteristics between lebrikizumab and tralokinumab may impact their respective clinical efficacies, with lebrikizumab potentially offering more effective neutralization of IL-13 due to its higher binding affinity.

From the Research

Binding Affinity Comparison

• The binding affinity of lebrikizumab and tralokinumab to IL-13 receptors has been compared in several studies 2, 3, 4.
• According to a study published in Dermatology and therapy, lebrikizumab bound IL-13 with higher affinity and slower off-rate compared to tralokinumab 2.
• The study used surface plasma resonance to determine the binding affinities and found that lebrikizumab had a higher affinity for IL-13 than tralokinumab 2.
• Another study published in Drugs in context reviewed the role of IL-13 in atopic dermatitis and the most recent data on lebrikizumab and tralokinumab, but did not provide a direct comparison of their binding affinities 3.
• A study published in Journal of cutaneous medicine and surgery discussed the inhibition of IL-13 as a new pathway for atopic dermatitis, but did not provide information on the binding affinities of lebrikizumab and tralokinumab 4.

Key Findings

• Lebrikizumab has a higher binding affinity for IL-13 than tralokinumab 2.
• Lebrikizumab has a slower off-rate than tralokinumab 2.
• Both lebrikizumab and tralokinumab have demonstrated acceptable safety profiles in clinical trials 3, 4.
• The clinical development of lebrikizumab and tralokinumab for the treatment of asthma has been halted indefinitely due to lack of efficacy 5.