An overview of the preclinical discovery and development of tezepelumab for the treatment of asthma

ABSTRACT

Introduction

Tezepelumab is a human IgG2 monoclonal antibody (mAb) that binds to human thymic stromal lymphopoietin (TSLP), preventing its interaction with the receptor and inhibiting multiple downstream inflammatory pathways. TSLP is an alarmin relevant to the pathogenesis of asthma.

Areas covered

This article focuses on the significance of TSLP in developing asthma and how tezepelumab can target it, thus playing a potentially relevant role in the treatment of asthma.

Expert opinion

An extensive clinical development program has shown that tezepelumab can improve all key primary and secondary endpoints in patients with severe asthma, compared to placebo, when added to standard therapy. Of particular importance is the favorable impact of this biological drug on exacerbation rates and lung function in patients with uncontrolled severe asthma regardless of the type 2 endotype. Therefore, tezepelumab is likely the first biologic to treat asthma exacerbations in patients with low eosinophil levels successfully. Furthermore, it appears to be a safe drug and can be ‘self-administered’ using a pre-filled, disposable pen. Tezepelumab should be preferred over other currently available biologics because blocking upstream mediators may have a broader therapeutic impact than those that inhibit downstream cytokines and/or block their receptors.

KEYWORDS:

• Asthma
• Alarmins
• TSLP
• Tezepelumab
• T2 status

Article highlights

• TSLP is a significant mediator of inflammation during allergic disease and a valuable target for therapeutic intervention.

• Tezepelumab is a human IgG₂ mAb that specifically binds human TSLP.

• Several phase 1 and 2 studies examined the PD, PK, and safety of tezepelumab, and the phase 3 PATHFINDER clinical development program documented this biologic’s efficacy in treating T2 and non-T2 asthma.

• Compared to placebo, when added to standard therapy, tezepelumab improved all key primary and secondary endpoints in patients with severe asthma. Of particular importance is the favorable impact of this biological drug on exacerbation rates and lung function in patients with uncontrolled severe asthma regardless of the T2 endotype.

• FDA and EMA approved tezepelumab for severe asthma. It can be ‘self-administered’ using a pre-filled, disposable pen.

Declaration of interest

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. This includes 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 manuscript was not funded.