Teprotumumab: a novel therapeutic monoclonal antibody for thyroid-associated ophthalmopathy

ABSTRACT

Introduction

Thyroid-associated ophthalmopathy (TAO) is a disfiguring, potentially blinding, and sub-optimally managed autoimmune condition. Current therapy of active TAO consists most frequently of glucocorticoid steroids, orbital radiation, or B-cell depletion; all of which are associated with substantial side effects. Teprotumumab (Tepezza) is a human monoclonal antibody against the insulin-like growth factor type I receptor (IGF-IR), recently evaluated in two clinical trials for active moderate-to-severe TAO that was recently approved by the United States Food and Drug Administration (FDA) for use in TAO.

Areas covered

This article reviews phase II and III placebo-controlled, double-masked, prospective, multicenter studies assessing the efficacy and safety of teprotumumab for the treatment of active, moderate-to-severe TAO.

Expert opinion

Teprotumumab has demonstrated substantial and rapid improvement in Clinical Activity Score and proptosis reduction in TAO compared to placebo. Subjective diplopia and quality of life were also improved in both clinical trials. Teprotumumab exhibited a favorable safety profile, with transient hyperglycemia, muscle cramps, and auditory side effects being associated with the drug; these were usually transient. The trial findings indicate that teprotumumab is a promising, potential first-line therapy for treating TAO.

KEYWORDS:

• IGF-IR
• Graves’ disease
• thyroid-associated ophthalmopathy
• thyroid eye disease
• R1507
• RV001
• teprotumumab
• Tepezza

Article Highlights

• Teprotumumab is a therapeutic monoclonal antibody that inhibits the insulin-like growth factor type I receptor (IGF-IR).

• It was studied in phase II and phase III trials for moderate-to-severe active thyroid-associated ophthalmopathy (TAO).

• Teprotumumab demonstrated substantial and rapid improvement in clinical activity, diplopia, and proptosis reduction.

• Teprotumumab is the only FDA approved therapy for TAO.

• Teprotumumab exhibited an overall favorable safety profile.

• Its long-term durability is currently being evaluated.

This box summarizes key points contained in the article.

Declaration of interest

TJ Smith's research is suppoted in part by NIH grants. He was issued U.S. patents for the use of inhibitors of IGF-IR in Graves’ disease, TAO, and other autoimmune diseases. U.S. Patents covered therapeutic targeting of IGF-I receptor (10/140,003, 13,710,635.8, 03/00187, 10/046,651, 10/038509). These are held by the Los Angeles Biomedical Foundation and UCLA School of Medicine. He serves as a paid consultant for Horizon Therapeutics and Immunovant. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has participated in the trials referred to in this paper. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

TJ Smith has received funding for his work from the following: NIH grant [EY008976], NIH grant [UM1 Al 110498 05], NEI Core grant [EY007003]