Amgen's Subcutaneous TEPEZZA Shows 77% Response Rate in Phase 3 Thyroid Eye Disease Trial
核心洞察
Amgen's Phase 3 trial of subcutaneous TEPEZZA demonstrated a statistically significant 77% proptosis response rate in moderate-to-severe active thyroid eye disease patients, compared to 19.6% with placebo.
The subcutaneous formulation delivered a clinically meaningful 3.17 mm reduction in eye bulging at 24 weeks, providing comparable efficacy to the approved intravenous version.
The on-body injector delivery system offers a more convenient treatment option for patients while maintaining the established safety profile of TEPEZZA.
Amgen announced positive topline results from a Phase 3 trial evaluating subcutaneous TEPEZZA (teprotumumab-trbw) administered via an on-body injector in patients with moderate-to-severe active thyroid eye disease (TED). The study met its primary endpoint, demonstrating a statistically significant 77% proptosis response rate during the 24-week placebo-controlled period compared to 19.6% with placebo (p<0.0001).
The subcutaneous formulation achieved a clinically meaningful mean proptosis reduction of 3.17 mm at week 24, significantly greater than the 0.80 mm reduction observed with placebo (p<0.0001). This represents a key secondary endpoint that underscores the therapeutic impact of the treatment.
"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."
Trial Design and Patient Population
The Phase 3, randomized, double-masked, placebo-controlled, parallel-group, multicenter trial evaluated the efficacy and safety of subcutaneous TEPEZZA versus placebo in patients with active TED. The primary endpoint was proptosis responder rate, defined as the percentage of participants achieving 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.
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 and proptosis of ≥3 mm from baseline prior to TED diagnosis. Notably, participants with baseline hearing impairment were allowed to participate in the study.
Comprehensive Efficacy Across Multiple Endpoints
The trial demonstrated statistically significant and clinically meaningful improvements across multiple secondary endpoints, including 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 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 from baseline at week 24 in the GO-QoL visual functioning subscale.
Safety Profile Consistent with IV Formulation
The overall safety results were generally consistent with the known safety profile of intravenous TEPEZZA. 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.
Clinical Impact and Expert Perspective
"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."
About Thyroid Eye Disease and TEPEZZA
TED is a serious, progressive and potentially vision-threatening rare autoimmune disease that often occurs in people living with Graves' disease. The condition is caused by autoantibodies activating an insulin-like growth factor-1 receptor (IGF-1R)-mediated signaling complex on cells within the retro-orbital space, leading to a cascade of potential vision-threatening effects.
TEPEZZA IV was approved in 2020 and remains the first and only approved medicine for TED, having treated more than 25,000 patients worldwide. The drug targets a root cause of the condition and has consistently demonstrated its ability to significantly reduce proptosis and double vision, two hallmark symptoms of TED, in multiple global clinical studies.
Post-Marketing Study Results
Additionally, Amgen completed a separate Phase 3b/4 trial conducted to fulfill an FDA post-marketing requirement for TEPEZZA IV. The study evaluated the safety and tolerability of three treatment durations (four, eight and 16 infusions) of TEPEZZA IV and assessed the need for retreatment. The observed risk profile was consistent with the known profile of TEPEZZA IV.