In April, the FDA approved an update to the TEPEZZA indication language, specifying its use in all patients with TED regardless of TED activity or duration. Horizon Therapeutics presented its data at the Endocrine Society's 2023 annual meeting in Chicago.
Horizon Therapeutics plc today announced the presentation of new data from the randomized, double-masked, placebo-controlled Phase 4 clinical trial (NCT04583735) evaluating teprotumumab-trbw (TEPEZZA, Horizon Therapeutics) in patients with long disease duration and low Clinical Activity Score (CAS), a measure of disease activity.
Teprotumumab-trbw is indicated for the treatment of thyroid eye disease (TED) regardless of TED activity or duration. The drug, a fully human monoclonal antibody inhibitor of IGF1, reduces inflammation and reverses retro-orbital tissue expansion and hyaluronan production by both binding to the IGF1 receptor/thyroid-stimulating hormone receptor–signaling complex and stopping the signaling at the source of the TED.
According to the company, the oral presentation at the Endocrine Society Annual Meeting (ENDO 2023) supports the efficacy and safety of teprotumumab-trbw in TED patients regardless of disease activity or duration. Teprotumumab-trbw is the first and only medicine approved by the FDA for the treatment of TED – a serious, progressive, debilitating and potentially vision-threatening rare autoimmune disease.1
“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 Thyroid Eye Disease for years and may have thought they were not a candidate for the medicine,” Raymond Douglas, MD, PhD, the principal investigator of the trial and director of the Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center in Los Angeles, said in the news release. “Thyroid Eye Disease is a heterogenous 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.”
The company previously reported the Phase 4 clinical trial met its primary efficacy endpoint (reduction in proptosis) and key secondary efficacy endpoint (proptosis responder rate). At Week 24, per the pre-specified primary analysis method (intent-to-treat), patients treated with teprotumumab-trbw achieved a 2.41 mm reduction in proptosis from baseline compared with 0.92 mm for placebo (p=0.0004) and 62% of patients treated with teprotumumab-trbw had a meaningful improvement in proptosis (≥2 mm) compared with placebo (25%) (p = 0.0134). In the pre-specified per-protocol analysis, patients treated with teprotumumab-trbw achieved a 2.44 mm reduction in proptosis from baseline compared with 0.69 mm for those receiving placebo (p = 0.0006) and 63% of patients treated with teprotumumab-trbw had a meaningful improvement in proptosis (≥2 mm) compared with placebo (7%) (p = 0.0008) at Week 24.
The company added the results presented at ENDO also showed that teprotumumab-trbw improved visual functioning as measured by Graves’ Ophthalmopathy Quality of Life Questionnaire (GO-QOL), a tool used to measure health-related quality of life in TED patients, scaled from 0 (worst) to 100 (best). At Week 24, in the pre-specified analysis in the intent-to-treat population, patients who received teprotumumab-trbw experienced a significantly greater average improvement from baseline for visual functioning (8.73) compared with placebo (2.41) (p=0.03). At Week 24, the change from baseline for appearance, also measured by GO-QOL, was 10.03 for TEPEZZA and 7.19 for placebo (p=0.65). The appearance subscale endpoint was not statistically significant: at Week 24, per the pre-specified primary analysis method (intent-to-treat), patients who received teprotumumab-trbw experienced a 10.03 improvement in appearance compared with 7.19 for placebo (p=0.65). No new safety signals were observed.
“Over the past few years, our understanding of Thyroid Eye Disease and the importance of TEPEZZA has continued to expand, fueled by the curiosity and efforts of leaders in the field and our combined commitment to ongoing research,” said Beth Scott, OD, MS, vice president, medical affairs, Horizon. “These trial data support the potential role of TEPEZZA across a broad range of Thyroid Eye Disease patients, no matter how long they have been living with the disease or how much disease activity they have.”
According to the company, the randomly assigned, 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 from two to 10 years duration prior to the study and have low 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 from baseline at Week 24.
The company noted all study participants were required to have an initial diagnosis of TED two to 10 years prior to screening, and a CAS of ≤1 in both eyes for at least one year prior to screening or all of the following one year prior to screening: no progression in proptosis, no progression in diplopia and no new inflammatory TED symptoms.
Horizon noted in its news release the participants could not have had prior orbital irradiation, orbital decompression surgery or strabismus surgery. The mean duration of disease for teprotumumab-trbw and placebo patients was 5.1 years (SD 1.88) and 5.4 years (SD 1.61), respectively. The mean CAS for TEPEZZA and placebo patients was 0.3 (SD 0.47) and 0.5 (SD 0.51), respectively.
1. Barrio-Barrio J, et al. Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:249125.