New era of targeted therapy begins for TED...'Tepezza' launches in KOR

Targets IGF-1R, improving proptosis and diplopia in patients...addressing the limitations of existing therapies

83% of the treatment group had over 2 mm proptosis reduction...reduced burden of surgery

Press conference was held to discuss 'Tepezza,' a treatment for thyroid eye disease (TED).

A targeted therapy that improves structural symptoms such as proptosis and diplopia in patients with thyroid eye disease (TED) has officially launched in South Korea.

​Until now, clinical practice has primarily utilized steroids to suppress inflammation, while considering surgical intervention if proptosis or diplopia persisted. With the addition of a drug that directly reduces proptosis by targeting the specific pathway involved in disease pathogenesis, treatment options for patients with moderate-to-severe disease are expected to broaden.

​On the 20th, Amgen Korea held a press conference at The Shilla Seoul to mark the domestic launch of the thyroid eye disease treatment 'Tepezza (teprotumumab),' presenting current domestic and international clinical landscapes and the drug's clinical value.

​Tepezza was approved by the Ministry of Food and Drug Safety (MFDS) on April 30 as a treatment for adult patients with moderate-to-severe thyroid eye disease. It is the first insulin-like growth factor-1 receptor (IGF-1R)- targeted therapy approved in South Korea for thyroid eye disease.

​Thyroid eye disease is an autoimmune condition causing inflammation and structural remodeling in orbital tissues, such as extraocular muscles and retrobulbar fat. Symptoms may include proptosis, diplopia, ocular pain, erythema, and edema, and severe cases can also impair visual acuity.

​Expanding beyond inflammation inhibition to proptosis reduction… "A 2 mm reduction is clinically significant"

​Professor Jin Sook Yoon, Department of Ophthalmology, Severance Hospital

Conventional pharmacotherapy for thyroid eye disease has largely focused on suppressing inflammation and immune responses.

​Although steroid-based therapies have been used for active moderate-to-severe patients, structural symptoms such as proptosis and diplopia can persist even after inflammation subsides. In such cases, surgical options such as orbital decompression or strabismus surgery are considered depending on the patient's condition.

​Tepezza is a monoclonal antibody targeting IGF-1R, which is involved in the pathophysiology of thyroid eye disease. This drug is differentiated from conventional immunosuppressive therapies by blocking IGF-1R signaling to inhibit orbital tissue inflammation and expansion.

​Professor Jin Sook Yoon of the Department of Ophthalmology at Severance Hospital highlighted the clinical significance of the proptosis reduction demonstrated with Tepezza therapy.

​Professor Yoon said, "Reducing proptosis by 2 mm previously required surgical interventions like orbital decompression," adding, "Broader surgical extents accompany risks of complications and may even induce de novo diplopia."

Professor Yoon explained that "Achieving a 2 mm reduction in proptosis with injectable pharmacotherapy alone is a significant metric."

​In the global Phase 3 OPTIC trial, Tepezza's therapeutic efficacy was evaluated over 24 weeks in patients with active, moderate-to-severe thyroid eye disease.

​The primary endpoint of proptosis response was defined as a reduction in proptosis of at least 2 mm from baseline without a corresponding worsening of 2 mm or more in the fellow eye.

​At week 24, the proptosis response rate was 83% in the Tepezza group compared to 10% in the placebo group. The mean reduction in proptosis differed significantly, measuring 2.82 mm in the Tepezza group versus 0.54 mm in the placebo group.

​Improvements were also observed in diplopia. Among patients presenting with diplopia at baseline, 68% in the Tepezza group improved by at least one grade, compared to 29% in the placebo group. The Tepezza group also demonstrated greater improvements in quality-of-life scores assessing the impact of visual function and aesthetic changes in TED patients.

​Tepezza is administered via intravenous infusion once every three weeks for a total of eight doses. In clinical trials, proptosis improved as early as six weeks after the initial dose, with therapeutic effects increasing throughout the treatment period.

​Application in moderate-to-severe patients… "Adverse reactions are manageable"

​Professor Don Kikkawa, Shiley Eye Institute, UC San Diego School of Medicine

With Tepezza's domestic introduction, determining which patient populations should receive priority treatment is expected to become a primary focus in real-world clinical practice.

​This is because individual TED patients present with differing degrees of proptosis, diplopia, and inflammation, as well as variations in disease activity and duration.

​Tepezza has been utilized in real-world clinical practice in the United States since its FDA approval in 2020. While initial adoption centered on patients with active moderate-to-severe thyroid eye disease, clinical experience and therapeutic use have progressively expanded to encompass chronic cases.

​Professor Don Kikkawa of the Shiley Eye Institute at the UC San Diego School of Medicine evaluated Tepezza as a key therapeutic option for moderate-to-severe patients requiring functional and structural improvement due to proptosis or diplopia.

​Professor Kikkawa said, "Tepezza is administered to patients seeking improvements in diplopia or proptosis," adding, "It is an exceptionally useful therapeutic option for moderate-to-severe thyroid eye disease patients."

​Professor Kikkawa added, "Adverse reactions during treatment are clinically manageable in practice. The vast majority of adverse events can be adequately addressed."

​Adverse events in the OPTIC study were predominantly mild to moderate, and key safety management parameters for Tepezza include hyperglycemia, muscle spasms, diarrhea, and hearing-related adverse events.

​Amgen is also continuing the development of a subcutaneous formulation to enhance administration convenience.

​In a recent global Phase 3 study evaluating the subcutaneous formulation delivered via an on-body injector, the 24-week proptosis response rate was 76.7% in the Tepezza group versus 19.6% in the placebo group. The mean proptosis reductions were 3.17 mm and 0.80 mm, respectively.

​Currently, only the intravenous formulation is approved in South Korea. Securing National Health Insurance reimbursement remains a key challenge for improving practical clinical access.

​Attention is focused on whether Tepezza can become a new treatment option for patients who previously had to consider surgical intervention due to residual proptosis and diplopia after controlling inflammation with conventional therapies.

​Suhee Shin, General Manager of Amgen Korea, stated that "While moderate-to-severe thyroid eye disease is a severe, rare autoimmune disease that profoundly impacts patients' daily and social lives through physical disfigurement and visual deterioration, therapeutic options had remained severely limited," and concluded by adding, "We hope that Tepezza's launch in South Korea would serve as a turning point for patients to reclaim their daily lives, affirming. Amgen will continue its efforts to establish a clinical setting where Korean patients can receive timely and appropriate care."