Investigational thymic stromal lymphopoietin inhibitors for the treatment of asthma: a systematic review

ABSTRACT

Introduction

Severe asthma patients often remain uncontrolled despite high-intensity therapies. Biological therapies targeting thymic stromal lymphopoietin (TSLP), a key player in asthma pathogenesis, have emerged as potential options. Currently, the only TSLP inhibitor approved for the treatment of severe asthma is the immunoglobulin G (IgG) 2λ anti-TSLP monoclonal antibody (mAb) tezepelumab.

Areas covered

This systematic review assesses the efficacy and safety of investigational TSLP inhibitors across different stages of development for asthma treatment.

Expert Opinion

TSLP contributes to airway inflammation, making it a pivotal therapeutic target. Ecleralimab, an inhaled antibody fragment antigen binding, shows promising evidence in enhancing efficacy and reducing systemic adverse events. SAR443765, with its NANOBODY® formulation and bispecific inhibition of TSLP and IL-13, offers improved tissue penetration and efficacy. The mAB TQC2731 exhibits high in vitro bioactivity, and the strength of the mAb UPB-101 is to act against the TSLP receptor. Some studies include mild and moderate asthma patients, suggesting the potential for extending biological therapy to non-severe patients. This systematic review highlights the potential of TSLP inhibitors as valuable additions to asthma treatment, even in milder forms of the disease. Future research and cost-reduction efforts are needed to expanding access to these promising therapies.

KEYWORDS:

• Investigational drugs
• experimental drugs
• efficacy and safety
• TSLP
• asthma
• monoclonal antibody
• nanobody
• fragment antigen binding

Article highlights

• To date, tezepelumab is the only TSLP-inhibitor authorized for the treatment of severe asthma. Several investigational TSLP-inhibitors are being developed.

• Ecleralimab (CSJ117), an inhaled anti-TSLP antibody fragment antigen binding (Fab), has proven effective and safe in a Phase I randomized clinical trial (RCT) on mild asthmatic patients.

• SAR443765, a bifunctional anti TSLP/IL-13 NANOBODY® molecule, has proven effective and safe in a Phase I RCT on mild-to-moderate asthmatic patients.

• TQC2731, an anti-TSLP IgG1 mAb, has proven safe and well tolerated in a Phase I CT on healthy subjects. A Phase II RCT is ongoing to assess the efficacy of TQC2731 in severe asthmatic patients.

• UPB-101, an anti-TSLP receptor IgG1 mAb, has proven safe and well tolerated in a Phase I CT on healthy subjects. A Phase Ib RCT is ongoing to assess the safety and tolerability of UPB-101 in mild asthmatic patients.

• Three RCT on TSLP inhibitors have enrolled non-severe asthmatic patients, suggesting a possible role of biological therapy for such patients in the future.

Declaration of interest

P. R. reports grants and personal fees from Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, MSD, Mundipharma, and Novartis, and participated as a lecturer and advisor in scientific meetings sponsored by Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, Edmond Pharma, GlaxoSmithKline, Menarini Group, Mundipharma, and Novartis. Her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, and Zambon.

No sponsor had a role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

G.M.M. has 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.

F.R.B. has 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.

M.D.A. has 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.

L.C. participated as an advisor in scientific meetings sponsored by Boehringer Ingelheim and Novartis, received non-financial support from AstraZeneca, a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Almirall, and is or was a consultant to ABC Farmaceutici, MSD, Recipharm, Zambon, Verona Pharma and Ockham Biotech. His department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis and Zambon.

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 paper was not funded.