Investigational anti IL-13 asthma treatments: a 2023 update

ABSTRACT

Introduction

IL-13 is a pleiotropic type 2 cytokine important in the pathogenesis of asthma and other eosinophilic disorders.

Areas covered

Different attempts to directly neutralize IL-13 or block its receptors and the possible impact that these approaches may have in the treatment of asthma.

Expert opinion

Collectively, specific anti-IL-13 agents are ineffective in treating severe asthma. Lebrikizumab and tralokinumab, the two most widely studied anti-IL-13 monoclonal antibodies, did not show any statistically significant improvement in quality of life or reduction in asthma exacerbation and/or symptoms in phase III studies. Consequently, their clinical development for the treatment of patients with asthma has been halted indefinitely. Other attempts to block or, at least limit, the impact of IL-13 in asthma, such as the use of protein-protein interaction modulators, kinase inhibitors, bispecific antibodies, or IL-13 peptide vaccines, are largely still in the preclinical stage of development, and it is difficult to predict whether they will reach clinical development. Nevertheless, since IL-13 directly affects airway contractility and is critical for mucus production and remodeling, and airflow limitation and mucus hypersecretion are commonly treatable features in asthma, we suggest including an anti-IL-13 drug before GINA step 5.

KEYWORDS:

• Asthma
• IL-13
• tralokinumab
• lebrikizumab
• kinase inhibitors

Article highlights

• IL-13 is a pleiotropic type 2 cytokine important in the pathogenesis of asthma and other eosinophilic disorders.

• It shares with IL-4 the type II receptor (IL-4RII), a heterodimer composed of IL-4 Rα and IL-13 Rα1. IL-13 Rα1 binds IL-13 with low affinity. IL-13 can also bind another receptor, IL-13 Rα2, which is known as a non-signaling decoy receptor of high affinity with IL-13.

• It is possible to neutralize IL-13 using monoclonal antibodies (mAbs) by blocking IL-13 binding to IL-13 Rα1 and IL-13 Rα2 (specific inhibition) or by blocking IL-13/IL-13 Rα1 complexes from recruiting IL-4 Rα while enabling IL-13 to interact with IL-13 Rα2 (dual IL4/IL13 inhibition)

• Clinical studies targeting IL-13 in asthma with tralokinumab (specific inhibition) and lebrikizumab (dual IL4/IL13 inhibition), the two most widely studied anti-IL-13 mAbs, have not produced clinically satisfactory results.

• Other attempts to block or, at least limit, the impact of IL-13 in asthma, such as the use of PPIMs, kinase inhibitors, bispecific antibodies, or IL-13 peptide vaccines, are largely still in the preclinical stage of development, and it is difficult to predict whether they will reach clinical development.

• Since IL-13 directly affects airway contractility and is critical for mucus production and remodeling and airflow limitation and mucus hypersecretion are commonly treatable features in asthma, it might be useful to include an anti-IL-13 drug before stage 5 suggested by the Global Initiative for Asthma strategy.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript, including employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.