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Innovent Biologics, Inc, a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases, announced that 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). As China’s first and the world’s second approved IGF-1R antibody drug, Sycume has ended a 70-year drought of no new treatment option for thyroid eye disease in China. This groundbreaking therapy will redefine the standard of care for thyroid eye disease.
Thyroid eye disease is an organ-specific autoimmune disorder closely associated with thyroid disease. It ranks first in the incidence of orbital diseases among adults, particularly prevalent in the age group of 40 to 60 years. The estimated annual incidence of TED is 16 per 100,000 people in women and 2.9 per 100,000 people in men, with a prevalence rate of 0.1-0.3%. TED can cause proptosis, orbital inflammation, diplopia and other clinical manifestations, which significantly impact a patient’s appearance, visual function, and quality of life. In severe cases, it can even lead to blindness.
At present, the first-line treatment for moderate-to-severe active TED is intravenous glucocorticoid (IVGC) therapy, although it has limitations, such as inadequate improvement in proptosis and systemic adverse reactions associated with steroid. Second-line treatments include a second course of IVGC, orbital radiotherapy, and other immunosuppressants with suboptimal outcomes. Recent Chinese and international treatment guidelines and joint consensus have recommended the use of IGF-1R-targeted biologics as a second-line treatment for TED. Particularly for patients with significant proptosis or diplopia, IGF-1R-targeted biologics can be considered the first-line treatment in such cases.
Prior to the approval of Sycume, only one IGF-1R antibody drug was approved globally and was not available in China. The cost of IGF-1R antibody oversea is extremely high, costing approximately 3 million RMB per treatment course. As China’s first IGF-1R antibody, Sycume offers robust efficacy and a favorable safety profile, providing a new and accessible treatment option for TED patients, with significant clinical and societal value. Additionally, Sycume adopts a liquid injection formation, which offers strengths in terms of stability, cost, manufacturing process simplicity, and patient compliance.
The approval is based on results from the phase 3 registrational study (RESTORE-1) in TED patients, which met its primary endpoint in 2024. The study showed 85.8% of patients achieved =2 mm proptosis reduction at week 24 with Sycume treatment, accompanied by significant improvements in inflammation and quality of life. The overall safety profile of Sycume was favorable throughout the study. RESTORE-1 results have been presented at premier conferences including World Ophthalmology Congress (WOC), Annual Meeting of Chinese Society of Endocrinology, and Congress of Chinese Ophthalmological Society, generating substantial recognition among experts.
Professor Xianqun Fan, an academician of the Chinese Academy of Engineering, Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, stated,” TED is the most common orbital disease in adults, and 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. Current first-line treatment for TED is glucocorticoids, though it has limitations, such as inadequate improvement in proptosis and notable side effects. Biologic agents targeting IGF-1R could to significantly improve proptosis and quality of life in TED patients and are expected to play an important role in its treatment. As an ophthalmologist and the principal investigator of the RESTORE-1 study, I am delighted with the approval of the first new TED drug in China. I hope that this drug will bring high-quality treatment option to TED patients as soon as possible. “
Dr. Lei Qian, senior vice president of Clinical Development of 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. The approval of Sycume not only highlights Innovent’s innovative R&D capabilities in the fields of ophthalmology and endocrinology but also reflects the high recognition of this product’s clinical value by regulatory authorities. It also marks another milestone of Innovent in the treatment of major diseases such as TED. Innovent will continue to focus on advancing innovation therapies to fulfill its commitment of serving more patients worldwide. “
Thyroid eye disease is an autoimmune disease involving ocular tissues, is the most common orbital disease in adults. 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.
The annual incidence of TED is estimated at 16 per 100,000 women and 2.9 per 100,000 men, with a prevalence of 0.1 to 0.3%. Based on disease severity, TED can be classified into mild, moderate to severe, or sight-threatening. While TED is more common in women, severe cases occur more frequently in men. The exact pathogenesis of TED is not fully understood, but multiple studies suggest that orbital fibroblasts in muscle fibers and orbital connective tissue play a key role in orbital soft tissue hyperplasia in TED.
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. In addition to affecting appearance and visual function, TED significantly impacts patients’ social functioning and quality of life.
At present, the first-line treatment for moderate-to-severe active TED is intravenous glucocorticoid (IVGC) therapy, though it has limitations, such as inadequate improvement in proptosis and systemic adverse reactions associated with steroid. Second-line treatments include a second course of IVGC, orbital radiotherapy, and other immunosuppressants with suboptimal outcome. Recent Chinese and international treatment guidelines and joint consensus have recommended the use of IGF-1R-targeted biologics as a second-line treatment for TED. Particularly for patients with significant proptosis or diplopia, IGF-1R-targeted biologics can be considered the first-line treatment in such cases.
Sycume (teprotumumab N01) is a recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody developed by Innovent for the treatment of TED. IGF-1R is a transmembrane tyrosine kinase receptor involved in development, metabolism, and immune regulation, and is overexpressed in OFs, B cells, and T cells of TED patients. Sycume blocks the activation of IGF-1R signaling pathway mediated by IGF-1 and related ligands or agonistic antibodies, reducing the expression of downstream inflammatory factors. This inhibition decreases the synthesis of hyaluronic acid and other glycosaminoglycans caused by OFs activation, thereby alleviating inflammation. It also prevents OFs differentiation into adipocytes or myofibroblasts, consequently reducing disease activity and improving clinical manifestations such as proptosis, diplopia, orbital congestion and edema.
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