Amgen Shares Positive Topline Phase 3 Data for Subcutaneous TEPEZZA® in Adults with Moderate-to-Severe Active Thyroid Eye Disease
Amgen (NASDAQ: AMGN) has announced positive topline results from a pivotal Phase 3 clinical trial evaluating a new method of administering TEPEZZA in patients with moderate-to-severe active Thyroid Eye Disease (TED). The study investigated a subcutaneous formulation delivered via an on-body injector (OBI), representing a potential evolution in how this first-in-class therapy is administered.
TEPEZZA is currently the first and only approved treatment specifically indicated for TED and has already been used to treat more than 25,000 patients globally. Until now, the therapy has been delivered exclusively through intravenous (IV) infusion. The development of a subcutaneous option aims to provide a more convenient and potentially more accessible mode of delivery while maintaining the therapy’s well-established clinical efficacy.
The Phase 3 trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in proptosis response rate, one of the most important measures of treatment effectiveness in TED. During the 24-week placebo-controlled period, 76.7% of patients treated with TEPEZZA OBI achieved a proptosis response, compared to just 19.6% in the placebo group. This difference was highly statistically significant, underscoring the robustness of the treatment effect.
Proptosis, commonly referred to as eye bulging, is one of the hallmark and most visible symptoms of TED. It can cause both physical discomfort and psychological distress for patients. In addition to the primary endpoint, the study also demonstrated significant improvements in a key secondary endpoint: mean reduction in proptosis. Patients receiving TEPEZZA via subcutaneous injection experienced an average reduction of -3.17 mm at week 24, compared to -0.80 mm in the placebo group. These results are consistent with the level of efficacy previously observed with IV administration, suggesting that the subcutaneous formulation can deliver comparable therapeutic benefits.
According to Jay Bradner, Executive Vice President of Research and Development at Amgen, the findings reinforce TEPEZZA’s position as a best-in-class therapy for TED. He emphasized that the introduction of a subcutaneous delivery method builds upon the medicine’s established clinical success and offers the potential to reach more patients by simplifying the treatment process. With a well-understood mechanism of action and a strong track record in clinical practice, TEPEZZA continues to evolve in ways that may enhance patient experience and broaden access.
Beyond the primary and key secondary endpoints, the trial also demonstrated statistically significant improvements across a range of additional secondary measures. These included overall responder rate, the proportion of patients achieving a low Clinical Activity Score (CAS of 0 or 1), and improvements in diplopia, or double vision, which is another debilitating symptom of TED. The study assessed diplopia using multiple metrics, including ordinal response categories, overall response rate, and complete response rate, all of which showed meaningful improvements in patients treated with TEPEZZA OBI compared to placebo.
Quality of life was another important focus of the trial. Patients receiving TEPEZZA OBI experienced significant improvements in the appearance subscale of the Graves’ Ophthalmopathy Quality of Life (GO-QoL) questionnaire, reflecting the impact of reduced proptosis and improved facial appearance. While the visual functioning subscale did not reach statistical significance, there was a favorable numerical trend for TEPEZZA OBI, suggesting potential benefits that may warrant further investigation. Full data from the study are expected to be presented at an upcoming medical congress, where a more comprehensive analysis of the results will be shared with the scientific and medical community.
The safety profile of TEPEZZA OBI was generally consistent with that of the IV formulation, which has been well characterized through prior clinical trials and real-world use. Most adverse events observed in the study were mild to moderate in severity. The most commonly reported side effects, occurring in at least 10% of patients, included muscle spasms, tinnitus (ringing in the ears), weight loss, ear discomfort, nausea, and diarrhea. These findings align with the known safety profile of TEPEZZA and provide reassurance that the subcutaneous formulation does not introduce unexpected safety concerns.
As expected with subcutaneous administration, some patients experienced injection site reactions. However, these reactions were generally mild to moderate and did not lead to treatment interruptions or discontinuations. This suggests that the on-body injector system is well tolerated and could be a viable alternative to IV infusion from a safety and usability perspective.
Thyroid Eye Disease is a serious and progressive autoimmune condition that affects the tissues around the eyes. It is often associated with Graves’ disease and can lead to a range of symptoms, including proptosis, diplopia, eye pain, redness, and swelling. In severe cases, TED can threaten vision and significantly impair daily functioning. The disease can also have a profound psychological impact due to changes in appearance and quality of life.
Madhura A. Tamhankar, a professor of ophthalmology and neurology at the Scheie Eye Institute at the University of Pennsylvania, highlighted the importance of expanding treatment options for patients with TED. She noted that the condition can be deeply debilitating, affecting not only vision but also everyday activities due to symptoms such as double vision and eye bulging. According to Dr. Tamhankar, the availability of a subcutaneous delivery option could make treatment more accessible and convenient for a broader range of patients, particularly those who may face challenges with IV infusions.
The introduction of an on-body injector represents a notable advancement in drug delivery technology within the field of ophthalmology. By enabling subcutaneous administration, the OBI system has the potential to reduce the need for infusion center visits, lower the burden on healthcare systems, and improve patient adherence to treatment. This approach aligns with broader trends in medicine toward more patient-centric care models, where convenience and accessibility are increasingly prioritized alongside efficacy and safety.
For Amgen, the development of TEPEZZA OBI reflects its broader commitment to innovation in both therapeutics and delivery systems. By enhancing how existing therapies are administered, the company aims to maximize their impact and ensure that more patients can benefit from them. The success of this Phase 3 trial represents an important step toward achieving that goal.
Looking ahead, the positive results from this study are expected to support regulatory submissions for the subcutaneous formulation of TEPEZZA. If approved, this new delivery option could significantly expand the reach of the therapy and provide patients with greater flexibility in how they receive treatment. It may also open the door to additional research exploring the use of subcutaneous delivery in other therapeutic areas.
In summary, the Phase 3 trial of TEPEZZA administered via an on-body injector has demonstrated compelling efficacy and a favorable safety profile in patients with moderate-to-severe active Thyroid Eye Disease. By achieving results comparable to the established IV formulation, the subcutaneous version offers a promising new option that combines clinical effectiveness with enhanced convenience. As Amgen continues to advance this innovation, TEPEZZA OBI has the potential to further transform the treatment landscape for TED, improving outcomes and quality of life for patients worldwide.
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 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.
About Thyroid Eye Disease (TED)
TED is a serious, progressive and potentially vision-threatening rare autoimmune disease.4 It often occurs in people living with Graves’ disease, but is a distinct disease that is caused by autoantibodies activating an insulin-like growth factor-1 receptor (IGF-1R)-mediated signaling complex on cells within the retro-orbital space.5,6 This can lead to a cascade of potential negative effects, which may be vision threatening.7,8 Early signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis; pressure and/or pain behind the eyes; and diplopia.
About TEPEZZA
TEPEZZA IV was approved in 2020 and remains the first and only approved medicine for TED and has changed the way the disease is treated by targeting a root cause of the condition. Its ability to significantly reduce proptosis and double vision – two hallmark symptoms of TED – has been consistently demonstrated in multiple global clinical studies2,3 and reinforced by six years of real-world experience in more than 25,000 patients.9,*
Source Link:https://www.amgen.com/
