5 minOn April 6, Amgen announced positive topline results from a Phase 3 clinical trial of its blockbuster drug TEPEZZA® (teprotumumab-trbw) administered via an on-body injector (OBI) for subcutaneous delivery in adult patients with moderate-to-severe active thyroid eye disease (TED). This new approach offers a more convenient treatment option with efficacy comparable to intravenous (IV) infusion.
The intravenous (IV) formulation of TEPEZZA was approved in 2020 and remains the first and only approved therapy for TED worldwide. By targeting the root cause of the disease, TEPEZZA has transformed the treatment landscape for TED and has benefited more than 25,000 patients globally to date.
Clinical Data: 77% of Patients Achieved Significant Proptosis Response
The newly released Phase 3 data are highly encouraging, with the study successfully meeting its primary endpoint. During the 24-week placebo-controlled period, patients treated with subcutaneous TEPEZZA demonstrated a highly statistically and clinically significant proptosis response rate.
- Primary Endpoint:
Up to 76.7% of patients in the TEPEZZA subcutaneous group achieved a proptosis response, compared to 19.6% in the placebo group (p < 0.0001). - Key Secondary Endpoint:
At Week 24, the mean reduction in proptosis was –3.17 mm in the treatment group versus –0.80 mm in the placebo group (p < 0.0001).
A reduction of more than 3 mm is considered highly clinically meaningful, significantly improving patients’ appearance and comfort.
In addition, statistically and clinically meaningful improvements were observed across multiple key secondary endpoints, including:
- Overall response rate
- Proportion of patients achieving a Clinical Activity Score (CAS) of 0 or 1
- Improvement in diplopia (double vision)
- Diplopia response rate and complete diplopia response rate
- Mean change from baseline in the Graves’ Ophthalmopathy Quality of Life (GO-QoL) appearance subscale at Week 24
Safety Profile
The overall safety profile of subcutaneous TEPEZZA was generally consistent with the known safety profile of the IV formulation. Some patients experienced mild to moderate injection-site reactions, but these did not lead to treatment interruption or discontinuation.
The most common adverse events (≥10%) included:
- Muscle spasms
- Tinnitus
- Weight loss
- Ear discomfort
- Nausea
- Diarrhea
Notably, the study included patients with pre-existing hearing impairment at baseline, which is a distinctive feature of this trial design.
Study Design
This Phase 3 trial was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Participants received subcutaneous injections of TEPEZZA or placebo via an on-body injector every two weeks, for a total of 12 doses.
Eligible patients were diagnosed with moderate-to-severe active TED within 15 months prior to enrollment and had a baseline proptosis of ≥3 mm.
Amgen also announced completion of a separate Phase 3b/4 trial evaluating the IV formulation of TEPEZZA (to meet FDA post-marketing requirements). This study assessed safety, tolerability, and the need for retreatment across three treatment durations (4, 8, and 16 infusions), with findings consistent with the known safety profile of TEPEZZA.
About Thyroid Eye Disease (TED)
Thyroid eye disease (TED) is a serious, progressive, and potentially vision-threatening rare autoimmune disease. Although it often occurs in patients with Graves’ disease, it is a distinct condition.
The disease is driven by autoantibodies that activate the insulin-like growth factor-1 receptor (IGF-1R) signaling complex on cells in the retro-orbital space, triggering inflammatory and tissue expansion processes that may threaten vision.
Early symptoms of TED include:
- Dry eyes
- Redness and swelling
- Excessive tearing
- Eyelid retraction
- Proptosis (eye bulging)
- Pressure or pain behind the eyes
- Diplopia (double vision)
There are approximately 4 million patients in China affected by TED.
