China's National Medical Products Administration (NMPA) has approved SYCUME® (teprotumumab N01), a recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody, for the treatment of thyroid eye disease (TED). Developed by Innovent Biologics, Inc. (HKEX: 01801), this approval marks a significant milestone as China's first and the world's second approved IGF-1R antibody drug for TED.
The approval ends a 70-year period without new treatment options for TED in China and is expected to redefine the standard of care for this debilitating condition.
A New Era for Thyroid Eye Disease Treatment
TED is an organ-specific autoimmune disorder closely associated with thyroid disease, ranking as the most common orbital disease in adults. It predominantly affects individuals between 40 and 60 years of age, with an estimated annual incidence of 16 per 100,000 women and 2.9 per 100,000 men. The disease causes proptosis (bulging eyes), orbital inflammation, diplopia (double vision), and other clinical manifestations that significantly impact patients' appearance, visual function, and quality of life. In severe cases, TED can lead to blindness.
Professor Xianqun Fan, an academician of the Chinese Academy of Engineering and principal investigator of the RESTORE-1 study, emphasized the impact of the disease: "TED is the most common orbital disease in adults, with proptosis being its most prominent clinical manifestation. The prolonged course of TED seriously impacts a patient's visual function and appearance, often leading to heavy psychological burden."
Clinical Evidence Supporting Approval
The NMPA approval is based on results from the Phase 3 registrational RESTORE-1 study, which met its primary endpoint in 2024. The study demonstrated that 85.8% of patients achieved ≥2 mm proptosis reduction at Week 24 with SYCUME® treatment. Patients also experienced significant improvements in inflammation and quality of life. The overall safety profile of SYCUME® was favorable throughout the study.
These results have been presented at premier medical conferences including the World Ophthalmology Congress (WOC), Annual Meeting of Chinese Society of Endocrinology (CSE), and Congress of Chinese Ophthalmological Society (CCOS), generating substantial recognition among experts.
Addressing Treatment Limitations
Until now, the first-line treatment for moderate-to-severe active TED has been intravenous glucocorticoid (IVGC) therapy, which has limitations including inadequate improvement in proptosis and systemic adverse reactions associated with steroids. Second-line treatments have included additional courses of IVGC, orbital radiotherapy, and other immunosuppressants, all with suboptimal outcomes.
Recent Chinese and international treatment guidelines now recommend IGF-1R-targeted biologics as a second-line treatment for TED. For patients with significant proptosis or diplopia, these biologics can even be considered as first-line treatment.
Dr. Lei Qian, Senior Vice President of Clinical Development at Innovent, stated: "As the first approved IGF-1R antibody and the first new TED therapy in China in 70 years, the development of SYCUME® has brought together the expertise of leading ophthalmology and endocrinology specialists."
Improved Accessibility and Formulation Advantages
Prior to SYCUME®'s approval, only one IGF-1R antibody drug was approved globally, and it was not available in China. That treatment costs approximately 3 million RMB (approximately $460,000 USD) per treatment course, making it prohibitively expensive for many patients.
SYCUME® offers several advantages beyond its clinical efficacy. It utilizes a liquid injection formulation, providing benefits in terms of stability, cost, manufacturing process simplicity, and patient compliance.
Mechanism of Action
SYCUME® works by blocking the activation of the IGF-1R signaling pathway. IGF-1R is a transmembrane tyrosine kinase receptor involved in development, metabolism, and immune regulation, and is overexpressed in orbital fibroblasts, B cells, and T cells of TED patients.
By inhibiting this pathway, SYCUME® reduces the expression of downstream inflammatory factors and decreases the synthesis of hyaluronic acid and other glycosaminoglycans caused by orbital fibroblast activation, thereby alleviating inflammation. It also prevents orbital fibroblast differentiation into adipocytes or myofibroblasts, consequently reducing disease activity and improving clinical manifestations such as proptosis, diplopia, and orbital congestion and edema.
Disease Burden and Impact
TED affects approximately 25% to 50% of Graves' disease patients, as well as individuals with other thyroid diseases and even those with normal thyroid function. While TED is more common in women, severe cases occur more frequently in men.
The natural progression of TED is divided into active and inactive stages. Common symptoms include dry eye, foreign body sensation, photophobia, lacrimation, diplopia, and pressure behind the eyes. Typical signs include upper eyelid retraction, proptosis, periorbital soft tissue congestion and edema, and ocular motility disorders.
While TED is usually mild to moderate-to-severe, about 3–5% of patients develop sight-threatening TED, which can result in vision-threatening corneal ulcers or compressive optic neuropathy. Beyond the physical symptoms, TED significantly impacts patients' social functioning and quality of life.
The approval of SYCUME® represents a significant advancement in the treatment landscape for TED in China, offering new hope for patients suffering from this debilitating condition.
