Horizon Therapeutics plc recently announced new data that provide important insights into the mechanisms of TEPEZZA™ (teprotumumab-trbw) for the treatment of Thyroid Eye Disease (TED). Two individual sets of findings were published in a special supplement of the Journal of the Endocrine Society and were also accepted as poster presentations at the Endocrine Society’s annual meeting (ENDO 2020). TEPEZZA is a fully human monoclonal antibody inhibitor of the insulin-like growth factor-1 receptor (IGF-1R), which received FDA approval earlier this year.
A population pharmacokinetic analysis was performed on data from the teprotumumab Phase 1 oncology clinical trial and Phase 2 and 3 TED clinical trials, evaluating the exposure-response relationship for efficacy. It 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 pharmacokinetic response based on patient demographics, including baseline age, gender, race, weight, smoking status, renal impairment or hepatic function.
“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. Information about the questionnaire has also been reported here.
“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.”
Full news release: https://ir.horizontherapeutics.com/news-releases/news-release-details/new-data-pharmacokinetic-profile-tepezzatm-teprotumumab-trbw
Source: Horizon Therapeutics