Horizon Therapeutics plc (NASDAQ:HZNP) today announced new data that provide important insights into the mechanisms of TEPEZZA™ (teprotumumab-trbw), illustrating its pharmacokinetic (PK) profile and supporting the dosing regimen established in the labeling for the treatment of Thyroid Eye Disease (TED). A separate abstract summarizes the first U.S.-based validation of the Graves' Ophthalmopathy Quality of Life (GO-QOL) questionnaire. Both studies were accepted as poster presentations at ENDO 2020, the Endocrine Society’s annual meeting. They were also published in a special supplement of the Journal of the Endocrine Society. TEPEZZA – the first and only medicine approved by the U.S. Food and Drug Administration (FDA) for TED – is a fully human monoclonal antibody (mAb) and a targeted inhibitor of the insulin-like growth factor-1 receptor (IGF-1R).
A population PK analysis was performed on data from the teprotumumab Phase 1 oncology clinical trial (n=60) and the Phase 2 and 3 TED clinical trials (N=83), evaluating the exposure-response relationship for key efficacy endpoints (proptosis response rate, percent of patients with a clinical activity score value of 0 or 1, and diplopia responder rate), as well as selected safety variables (hyperglycemia and muscle spasms).
The analysis found that in TED patients, TEPEZZA had a long elimination half-life, low systemic clearance and low volume of distribution, consistent with other monoclonal antibodies. There was no meaningful exposure-response relationship at the selected dose regimen for both efficacy and safety endpoints. There also were no significant differences in PK response based on patient demographics, including baseline age, gender, race, weight, smoking status, renal impairment (mild/moderate) or hepatic function (total bilirubin, aspartate and alanine aminotransferases).
“The TEPEZZA clinical development program evaluated the efficacy and safety of an initial infusion of 10 mg/kg followed by seven infusions of 20 mg/kg once every three weeks,” said Elizabeth H.Z. Thompson, Ph.D., group vice president, development and external search, research and development, Horizon. “This PK analysis provides further evidence that the dosing used in the clinical trials, which is now part of the product labeling, is appropriate and also consistent across various patient types.”
A separate abstract summarizes the first U.S.-based validation of the GO-QOL questionnaire. In the Phase 2 and Phase 3 TEPEZZA clinical trials, the GO-QOL questionnaire was used to evaluate QOL changes in patients who received TEPEZZA compared with placebo. The GO-QOL questionnaire includes eight questions each on visual functioning and appearance-related impacts. Though widely used and validated in Europe, the questionnaire has not previously been validated in the United States. For this evaluation, 13 eligible TED patients completed the questionnaire and then underwent a separate cognitive QOL-related interview. Qualitative interviews indicated that patients found the GO-QOL content relevant and complete.
The most commonly reported visual functioning impacts included the following:
- Difficulty driving (92 percent)
- Difficulty using electronic screens, such as televisions, smart phones and computers (77 percent)
- Difficulty moving around outdoors, due to things like light sensitivity, uneven surfaces and depth perception (69 percent)
- Difficulty doing hobbies (69 percent)
Frequently reported emotional and psychological impacts included the following:
- Change in appearance (92 percent)
- Depression and anxiety (77 percent)
- Frustration and anger (69 percent)
- Negative reactions from others, social impacts and isolation, and lack of self-confidence and embarrassment (each 62 percent)
“Part of Horizon’s goal in introducing novel therapies is to meaningfully improve the state of care for the community, and we believe the assessment of the GO-QOL questionnaire for U.S. patients will help physicians quantify the true burden of this disease as they make treatment decisions for their patients,” said Thompson. “Taken together, these studies offer further insights into TEPEZZA and TED – supporting the important role TEPEZZA plays in helping physicians address the devastating effects of this challenging disease.”