Amgen announced in a press release positive topline results from a phase 3 trial of Tepezza (teprotumumab-trbw) administered by subcutaneous injection via an on-body injector (OBI) in participants with moderate-to-severe active thyroid eye disease (TED). Tepezza OBI provides comparable efficacy to, and builds upon intravenous (IV) Tepezza, which was approved for the treatment of TED, the company said.
The phase 3 Tepezza OBI trial met its primary endpoint in moderate-to-severe active TED, showing a statistically significant and clinically meaningful 77% proptosis response rate during the 24-week placebo-controlled period (76.7% Tepezza OBI vs 19.6% placebo [P<0.0001]). The mean proptosis reduction, a key secondary endpoint, was -3.17 mm at week 24 (-3.17 mm Tepezza OBI vs -0.80 mm placebo; P<0.0001).
According to the company, the trial also showed statistically significant and clinically meaningful improvements across the following additional secondary endpoints: overall responder rate; percentage of patients achieving a Clinical Activity Score (CAS) of 0 or 1; change in diplopia as ordinal response categories; diplopia response rate; complete diplopia responder rate; and mean change from baseline in week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) appearance subscale. Although not statistically significant, the company said there was a numerical trend favoring Tepezza OBI in the mean change in baseline at week 24 in the GO-QoL visual functioning subscale. Full results from the study will be presented at an upcoming medical congress, the Amgen said in the press release.
The overall safety results were generally consistent with the known safety profile of Tepezza IV.1,2 Mild-to-moderate injection site reactions were observed with subcutaneous administration in some patients, which did not result in treatment interruption or discontinuation. The most common adverse events (≥10%) were muscle spasms, tinnitus, weight decrease, ear discomfort, nausea and diarrhea, according to the company.
About the Phase 3 Tepezza OBI Trial
This phase 3, randomized, double-masked, placebo-controlled, parallel-group, multicenter trial was to evaluate the efficacy and safety of subcutaneous Tepezza vs placebo in patients with active TED. The primary endpoint was proptosis responder rate (percentage of participants with a ≥2-mm reduction from baseline in proptosis in the study eye without deterioration [≥2-mm increase] of proptosis in the fellow eye) at Week 24.
During the study, participants received Tepezza or placebo via an on-body injector every 2 weeks for a total of 12 injections. Inclusion criteria required a diagnosis of moderate-to-severe active TED within 15 months, as well as proptosis of ≥3 mm from baseline (prior to TED diagnosis), among other factors. Participants with baseline hearing impairment, whether identified through medical history or audiogram, were allowed to participate in the study, the company said.
Tepezza IV Post-Marketing Requirement Study
In addition, a separate phase 3b/4 trial, conducted to fulfill an FDA post-marketing requirement for Tepezza IV, has been completed. According to the company, the primary objective of the study was to evaluate the safety and tolerability of 3 treatment durations (4, 8, and 16 infusions) of Tepezza IV and assess the need for retreatment. The study was descriptive in nature. The observed risk profile was consistent with the known profile of Tepezza IV. The post-marketing data will be submitted to regulatory authorities and presented at an upcoming medical congress, the company concluded.
References
1. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748-1761. doi:10.1056/NEJMoa1614949
2. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382(4):341-352. doi:10.1056/NEJMoa1910434