This study (CTR20223393) is a randomized, double-blinded, placebo-controlled, phase 2 clinical study in TAO subjects. The primary objective was to evaluate the efficacy of IBI311 in improving proptosis in TAO subjects to support further clinical development of IBI311 advancing into pivotal studies.
IBI311 is an IGF-1R targeting monoclonal antibody independently developed by Innovent. By blocking the binding of IGF-1 and IGF-2 to IGF-1R, IBI311 inhibits IGF-1R signaling pathway activation and reduces the expression of downstream inflammatory factors, thereby inhibiting the adipocytosis of orbital fibroblasts (OFs) and the synthesis of hyaluronic acid and other glycosaminoglycans due to the activation of OFs, as well as the inflammatory response, thus reduces disease activity and improve proptosis, diplopia, ocular congestion and edema in patients with active TAO. Currently, no targeted drugs for TAO have been approved in China; overseas, Teprotumumab is the first and currently only IGF-1R mAb approved by the FDA for TAO.
The principal investigator, Professor Fan Xianqun from Ophthalmology Department of the Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, an academician from the Chinese Academy of Engineering, stated: " Thyroid-associated ophthalmopathy is one of the most common orbital diseases in adults and is an organ-specific autoimmune disease closely related to thyroid disease, which can severely affect the visual function and appearance of patients. There are currently no targeted drugs approved for TAO in China. In 2020, Teprotumumab was approved by the FDA for the treatment of TAO, providing a new option for TAO treatment, and was recommended by the Chinese Clinical Diagnosis and Treatment Guidelines for Thyroid Associated Ophthalmopathy (2022), the European Group On Graves' Orbitopathy (EUGOGO) and the consensus on thyroid eye disease of the American Thyroid Society and the European Thyroid Society. We are looking forward to IBI311, developed by a domestic biopharmaceutical company, demonstrating good efficacy and safety in the Chinese TAO population and being able to be approved and launched to market as soon as possible to relieve patients' pain."
Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated: "At present, there is a great unmet medical need for TAO because of no targeted drug approved for TAO in China. IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent for the treatment of TAO and also another new molecule laid out by Innovent in the field of ophthalmology, with high druggability. Preclinical in vivo and in vitro studies have preliminarily verified that IBI311 has good safety and biological activity. The Phase 1 study in healthy volunteers also demonstrated favorable safety and tolerability of IBI311 and provide the basis for further clinical development. I believe that IBI311 will demonstrate encouraging efficacy and safety date in the current phase 2 clinical study of in TAO subjects. Innovent will cooperate with academia and promote clinical development under the leadership of Prof. Fan to bring high quality and accessible biologics to TAO patients, truly fulfilling our mission of 'To develop and commercialize high-quality biopharmaceuticals that are affordable to ordinary people ' ."
Thyroid associated ophthalmopathy (TAO) is an autoimmune disease involving ocular tissues and is usually associated with Graves' disease (GD) and is the most common orbit-related disease in adults. TAO occurs in approximately 25 to 50% of GD patients and can also be seen in other thyroid diseases, even in euthyroidism1.The annual incidence of TAO is estimated to be 16/100,000 in women and 2.9/100,000 in men2. According to disease severity, it can be divided into mild, moderate and severe. Although TAO appears to affect women more often, severe cases occur more frequently in men. Patients aged 30 to 50 years are most commonly affected, and severe cases occur more frequently in patients over 50 years3. At present, the pathogenesis of TAO is not fully understood, but several studies have shown that OFs present in muscle fibers, orbital fibrous connective tissue space are key factors leading to orbital soft tissue enlargement in TAO4.
Currently, the first-line treatment option for moderately severe active TAO is intravenous glucocorticoid therapy, which suffers from unsatisfactory improvement of proptosis and systemic side effects, and second-line treatment includes other immunomodulators, which also have risks related to unclear improvement of proptosis and treatment.
Teprotumumab is recommended by the Chinese Clinical Diagnosis and Treatment Guidelines for Thyroid Associated Ophthalmopathy (2022)7, the European Group On Graves' Orbitopathy (EUGOGO)8 and the consensus on thyroid eye disease of the American Thyroid Society and the European Thyroid Society9 as a second-line treatment option for moderately severe active TAO. There is still a large unmet clinical need in China.
IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent Biopharmaceuticals. IGF-1R is a transmembrane tyrosine kinase receptor that plays a role in development, metabolism, and immune regulation, and is overexpressed in OFs, B, and T cells of thyroid ophthalmopathy in Graves' disease10. IBI311 can bind IGF-1R, block IGF-1R signaling pathway activation mediated by IGF-1 and other related ligands or agonistic antibodies, reduce the expression of downstream inflammatory factors, thereby inhibiting the synthesis of hyaluronic acid and other glycosaminoglycan caused by OFs activation, as well as related inflammatory reactions including tissue congestion and edema; inhibit adipocyte cellularization of OFs, thereby reducing the disease activity of patients with active thyroid ophthalmopathy and improving proptosis, diplopia, ocular congestion and edema and other symptoms and signs.
Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines in the fields of oncology, metabolism, autoimmunity,, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.
Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 36 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor), olverembatinib (BCR-ABL TKI) , Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 3 assets are under NMPA NDA review, 6 assets are in Phase 3 or pivotal clinical trials, and 19 more molecules are in clinical studies.
Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with EliLilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.
Note:
TYVYT® (sintilimab injection) is not an approved product in the United States.
1. This indication is still under clinical study, which hasn't been approved in China.
2. Innovent does not recommend any off-label usage.
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