Autoimmune blistering diseases: promising agents in clinical trials

ABSTRACT

Introduction

Treatment options for autoimmune bullous diseases (AIBD) are currently limited to corticosteroids and traditional immunomodulants and immunosuppressants that are associated with unfavorable adverse effect profiles. The most frequent AIBDs, i.e. bullous pemphigoid, pemphigus vulgaris, and mucous membrane pemphigoid, impose a high disease burden onto affected patients and can be detrimental due to infections, exsiccosis, and impaired food intake. Significant progress has been made in elucidating disease mechanisms and key mediators by in vivo and in vitro models, thus identifying a multifaceted range of possible drug targets. However, except for rituximab for pemphigus vulgaris, no new drugs have been approved for the treatment of AIBDs in the last decades.

Areas covered

This review covers new drug developments and includes ongoing or completed phase 2 and 3 clinical trials. Studies were identified by querying the registries of ClinicalTrials.gov and Cochrane Library.

Expert opinion

Promising results were shown for a variety of new agents including nomacopan, efgartigimod, omalizumab, dupilumab, as well as chimeric autoantibody receptor T cells. Clinical translation in the field of AIBDs is highly active, and we anticipate significant advances in the treatment landscape.

KEYWORDS:

• autoimmune bullous diseases
• bullous pemphigoid
• chimeric autoantigen receptor
• dupilumab
• efgartigimod
• mucous membrane pemphigoid
• nomacopan
• pemphigus vulgaris

Article highlights

• Current therapy options in autoimmune bullous diseases are limited to corticosteroids, immunomodulants, such as dapsone and tetracyclines, immunosuppressants, IVIG, and rituximab. More efficient and safe options are urgently needed.

• Efgartigimod, an inhibitor of the neonatal Fc receptor, showed promising results in both pemphigus and pemphigoid diseases, and drug development is very advanced.

• Nomacopan, a dual inhibitor of complement C5a and leukotriene B₄, showed very encouraging preliminary results in BP patients, however, testing is halted. Complement inhibitors could provide a new therapy option in pemphigoid diseases.

• The anti-IL-4 receptor antibody dupilumab and benralizumab, an antibody against the IL-5 receptor, are currently explored in randomized controlled phase 3 studies in BP.

• In the next 5 years, licensing of efgartigimod for pemphigus and BP as well as for dupilumab and benralizumab in BP are anticipated if the current ongoing phase 3 studies can be evaluated positively.

• Unfortunately, for all other pemphigoid diseases, no new drug will be licensed in the next 5 years.

Declaration of interest

ES has research cooperations with UCB, Incyte, Biotest, ArgneX, Dompe, Admirx, Biondis, Fresenius Medical Care, Pharmaxis, Alpine Immune, Bayer, CSL, AstraZeneca, and Pincell. ES received honoraria or travel grants from Biotest, ArgenX, Sanofi, Fresenius Medical Care, AstraZeneca, Leo, Chugai, Sanofi, and Almirall. CDS co-filed a pending patent on the use of nomacopan for bullous pemphigoid. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Author contributions

HO drafted the manuscript. CDS and ES revised the manuscript. All authors approved the submitted version.

Additional information

Funding

This work was supported by the Clinician Scientist School Lübeck (CS01-2022), funded by the University of Lübeck, and by the Cluster of Excellence Precision Medicine in Chronic Inflammation (EXC 2167) funded by the Deutsche Forschungsgemeinschaft and the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig-Holstein.