Primary and Key Secondary Endpoints Met

77% of Patients Achieved Highly Statistically Significant Proptosis Response

Study Showed Clinically Meaningful Reduction in Proptosis; Greater Than 3 mm

Amgen announced 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 the success of, intravenous (IV) TEPEZZA, the first and only medicine approved for the treatment of TED, which has now treated more than 25,000 patients worldwide.

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]). Importantly, 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).

"These results extend and support the best-in-class efficacy of TEPEZZA for people living with Thyroid Eye Disease, now with subcutaneous administration delivering IV-level efficacy," said Jay Bradner, M.D., executive vice president of Research and Development at Amgen. "With a well-understood mechanism and established impact in the clinic, we can evolve how the medicine is delivered to potentially reach even more patients through a more convenient subcutaneous option."

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, 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 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.

TED is a serious, progressive and potentially vision-threatening rare autoimmune disease that can cause proptosis (eye bulging), diplopia (double vision), eye pain, redness and swelling.³

"Thyroid Eye Disease can be a profoundly debilitating condition, affecting not only vision but also daily functioning with symptoms like double vision and eye bulging," said Dr. Madhura A. Tamhankar, M.D., professor of ophthalmology and neurology at the Scheie Eye Institute, University of Pennsylvania. "Expanding administration options through subcutaneous delivery opens the possibility of a more accessible experience for patients with Thyroid Eye Disease and is critical to serving diverse patient needs. The potential to achieve comparable efficacy to IV makes this advancement compelling."

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 two 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. Of note, participants with baseline hearing impairment, whether identified through medical history or audiogram, were allowed to participate in the study.

TEPEZZA IV Post-Marketing Requirement Study
Additionally, a separate Phase 3b/4 trial, conducted to fulfill an FDA post-marketing requirement for TEPEZZA IV, has been completed. The primary objective of the study was to evaluate the safety and tolerability of three treatment durations (four, eight 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.