Phase 4 Trial Data Supports Efficacy of Teprotumumab-trbw for Thyroid Eye Disease

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Additional phase 4 trial results presented at ENDO 2023 reinforce the efficacy and safety of teprotumumab-trbw in eyes with TED, regardless of disease activity or duration.

New phase 4 clinical trial data reinforce the efficacy of teprotumumab-trbw (TEPEZZA®) in patients with thyroid eye disease (TED), regardless of disease activity or duration, according to research presented at the Endocrine Society Annual Meeting.1

The findings, announced in a release by Horizon Therapeutics, follow an update to the teprotumumab-trbw indication language approved by the US Food and Drug Administration (FDA) in April, indicating the therapy's use in all patients with TED regardless of disease activity or duration.2

“Over the past few years, our understanding of TED and the importance of TEPEZZA has continued to expand, fueled by the curiosity and efforts of leaders in our field and our combined commitment to ongoing research,” Beth Schott, OD, MS, vice president of medical affairs at Horizon Therapeutics said in a statement.1 “These trial data support the potential role of TEPEZZA across a broad range of TED patients, no matter how long they have been living with the disease or much disease activity they have.”

The randomized, double-masked, placebo-controlled, parallel-group, multicenter trial evaluated the efficacy, safety, and tolerability of teprotumumab-trbw (n = 42) compared to placebo (n = 20) in adults who have lived with TED for a duration of 2 - 10 years and have low Clinical Activity Score (CAS). The primary efficacy objective was to measure the effect of teprotumumab-trbw versus placebo in the change of proptosis measurements in the study eye at Week 24, with a key secondary efficacy endpoint of proptosis responder rate.

As indicated, the phase 4 clinical trial met both its primary and key secondary efficacy endpoints. At Week 24, patients in the intent-to-treat population treated with teprotumumab-trbw saw a 2.41 mm reduction in proptosis from baseline compared with 0.92 mm for placebo (P = .0004). The analysis further revealed 62% of patients treated with teprotumumab-trbw experienced meaningful improvements in proptosis (≥2 mm) compared with 25% of those treated with placebo (P = .0134).3

Results presented at ENDO 2023 suggest teprotumumab-trbw improved visual functioning based on Graves’ Ophthalmopathy Quality of Life Questionnaire (GO-QOL) scores, measured from 0 (worst) to 100 (best).1 At Week 24, in the pre-specified analysis of the intent-to-treat population, those treated with teprotumumab-trbw experienced a significantly greater average visual functioning improvement from baseline (8.73) compared with placebo (2.4) (P = .03). However, the change from baseline for appearance measured by GO-QOL was 10.03 for teprotumumab-trbw and 7.19 for placebo (P = .65) and was not considered statistically significant.

Meanwhile, the research suggests the proportion of patients with adverse events was comparable between patients treated with teprotumumab-trbw and those treated with placebo. Study investigators observed no new safety signals related to the treatment. The most common adverse reactions (incidence ≥5%) related to the treatment include muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, weight decreased, nail disorders, and menstrual disorders.

“These data are important because they provide evidence in a controlled, clinical setting that TEPEZZA can significantly improve proptosis and visual functioning as measured by the Graves’ Ophthalmopathy Quality of Life Questionnaire in people who have been living with TED for years and may have thought they were not a candidate for the medicine,” Raymond Douglas, MD, PhD, principal trial investigator and director of the Orbital and Thyroid Eye Disease program at Cedars-Sinai Medical Center.1 “TED is a heterogeneous disease, and its impact is not always immediately visible, affecting patients both physically in day-to-day activities and mentally due to the emotional distress that accompanies the disease. It is not too late to help those patients with longer-term symptoms.”


  1. Additional data from phase 4 TEPEZZA® (teprotumumab-TRBW) clinical trial presented at the endocrine society annual meeting reinforces efficacy in people with thyroid eye disease (ted) regardless of disease activity or duration. Horizon Therapeutics plc. June 17, 2023. Accessed June 19, 2023.
  2. Iapoce C. FDA approves update to indication language for teprotumumab in thyroid eye disease. HCP Live. April 14, 2023. Accessed June 19, 2023.
  3. Iapoce C. Phase 4 trial reports positive data on teprotumumab for thyroid eye disease. HCP Live. April 10, 2023. Accessed June 19, 2023.