Subcutaneous Tepezza Demonstrates Phase III Efficacy in Thyroid Eye Disease

A subcutaneous option may expand access and convenience while maintaining efficacy in Thyroid Eye Disease treatment. Amgen announced positive topline results from a phase 3 trial evaluating a subcutaneous (SC) formulation of teprotumumab-trbw (brand name Tepezza) in adults with moderate-to-severe active thyroid eye disease (TED), demonstrating significant improvements in disease outcomes compared with placebo.1

The randomized, placebo-controlled study met its primary endpoint, with 76.7% of patients receiving SC teprotumumab-trbw achieving a proptosis response, defined as a ≥2 mm reduction in eye bulging, at week 24, compared with 19.6% in the placebo arm (p<0.0001). The therapy also met a key secondary endpoint, showing a mean proptosis reduction of –3.17 mm versus –0.80 mm with 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 [intravenous]-level efficacy,” said Jay Bradner, executive vice president of research and development at Amgen, in a company press release.1 “We can evolve how the medicine is delivered to potentially reach even more patients through a more convenient subcutaneous option.”

Beyond the primary endpoint, the trial demonstrated statistically significant improvements across multiple secondary measures, including overall response rate, Clinical Activity Score, and diplopia outcomes. Patients also reported improved quality of life based on the Graves’ Ophthalmopathy Quality of Life appearance subscale. A numerical trend favoring teprotumumab-trbw was observed in visual functioning scores, though this did not reach statistical significance.

What is the significance of subcutaneous delivery in TED?

TED is a rare, progressive autoimmune condition that can lead to proptosis, double vision, pain, and potential vision loss. It is commonly associated with Graves' disease and is driven in part by activation of insulin-like growth factor-1 receptor (IGF-1R) signaling pathways.

Historically, teprotumumab-trbw has been administered intravenously and remains the only approved therapy for TED. While effective, IV administration can present logistical challenges for patients and providers.2 The development of a SC, on-body injector formulation reflects a broader effort to improve treatment accessibility and convenience without compromising efficacy.

“Expanding administration options through subcutaneous delivery opens the possibility of a more accessible experience for patients,” said Madhura A. Tamhankar, MD, professor of ophthalmology and neurology at the Scheie Eye Institute at the University of Pennsylvania. “The potential to achieve comparable efficacy to IV makes this advancement compelling.”

Safety findings from the trial were consistent with the known profile of intravenous teprotumumab-trbw. The most common adverse events included muscle spasms, tinnitus, nausea, diarrhea, and weight decrease. Injection site reactions were generally mild to moderate and did not lead to treatment discontinuation.

What are the broader implications for treatment strategies?

The phase 3 results highlight a growing trend in biopharmaceutical development that involves optimizing not only therapeutic efficacy but also mode of delivery to improve patient experience and expand real-world use. SC formulations, particularly those delivered via on-body injectors, are increasingly being explored across therapeutic areas to reduce treatment burden and conserve healthcare resources.3

For Amgen, these findings support the clinical value of targeting IGF-1R in TED and may encourage future regulatory discussions aimed at broadening administration options for teprotumumab-trbw. If approved, the SC formulation could further establish the biologic as a foundational therapy in TED while improving treatment accessibility.

More broadly, the study underscores continued innovation in rare autoimmune diseases, for which advances in both mechanism-driven therapies and patient-centric delivery approaches are reshaping standards of care.

References

1. Amgen. Amgen announces positive topline phase 3 results for subcutaneous Tepezza in adults living with moderate-to-severe active thyroid disease. Published April 6, 2026. Accessed April 7, 2026. https://www.amgen.com/newsroom/press-releases/2026/04/amgen-announces-positive-topline-phase-3-results-for-subcutaneous-tepezza-in-adults-living-with-moderate-to-severe-active-thyroid-eye-disease

2. Perros P, Hegedüs, L. Teprotumumab in thyroid eye disease: wonder drug or great divider? Eur Thyroid J. 2023 Jun 12;12(4):e230043. doi: 10.1530/ETJ-23-0043

3. James D. Phase III IRAKLIA and Phase II IZALCO trials support sarclisa on-body delivery for relapsed/refractory multiple myeloma. Applied Clinical Trials. June 6, 2025. https://www.appliedclinicaltrialsonline.com/view/iraklia-izalco-sarclisa-relapsed-multiple-myeloma