Innovent Biologics announced that the NDA for tetumumab (IGF-1R antibody) has been accepted by the National Medical Products Administration (NMPA) for the treatment of thyroid eye disease

SAN FRANCISCO and SUSU, China, May 21, 2024 /PRNewswire/ -- Innovent Biologics Group (HKEX: 01801), a biopharmaceutical company dedicated to the development, production and marketing of innovative drugs for oncology, autoimmune, metabolic, cardiovascular, ophthalmology and other major diseases, today announced: Tetumumab Injection (recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody, IBI311) has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China for the treatment of Thyroid Eye Disease (TED). As a biologic drug with an innovative mechanism of action, tetumumab is the first IGF-1R antibody to be marketed in China, which is expected to fill the gap in the field of TED treatment in China for 60 years, meet the significant clinical needs of TED treatment in China, and bring effective, safe and accessible treatment methods to TED patients in China.

The NDA acceptance was based on the positive results of RESTORE-1 (CTR20223393), a Phase III registrational clinical study in TED subjects in China. The study successfully met its primary endpoint in February 2024 and showed that the IBI311 group had significantly better improvements in proptosis, disease activity, and quality of life than the placebo group. During the study treatment, the overall safety profile of tetumumab was good, and no new safety signals were identified. Detailed data from the RESTORE-1 study are planned to be published at the 2024 academic conference and in academic journals.

As an autoimmune disease affecting the tissues of the eye, the estimated annual incidence of TED is 16 per 100,000 women and 2.9 per 100,000 men [1], with a prevalence of 0.1 to 0.3 percent [2]. At present, for TED treatment, a number of clinical treatment guidelines at home and abroad have included IGF-1R-targeting antibody biologics in the recommended treatment regimen [3], [4], [5], especially for TED with significant eye protosis, IGF-1R-targeting antibody biologics can be the first choice, and no similar targeted drugs have been approved for marketing in China. Therefore, effective, safe and accessible IGF-1R-targeting drugs have important clinical and social value for Chinese TED patients.

The principal investigator of the study, academician of the Chinese Academy of Engineering, and professor of the Department of Ophthalmology of the Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine

"Thyroid ophthalmopathy is one of the most common orbital diseases in adults, and proptosis is its most important clinical manifestation," he said. The prolonged course of thyroid eye disease seriously affects the visual function and appearance of patients, and can bring a heavy psychological burden to patients. At present, the treatment methods of TED in China are limited, and the efficacy of existing therapeutic drugs in relieving proptosis is unclear and the side effects are obvious, and there is a great unmet clinical need. Tetumumab has demonstrated excellent efficacy in clinical studies to improve proptosis and orbital soft tissue inflammation with a good safety profile. I am excited about the breakthrough of China's in-house developed and manufactured tetumumab in the field of TED treatment, and I am proud that I have successfully completed the clinical study with researchers from the National Participating Research Center and supported the successful submission of this NDA. It is expected that tetumumab will be launched as soon as possible to benefit TED patients in China. "

Dr. Lei Qian, Clinical Vice President of Innovent Biologics Group

"We are honored that with the support of regulators, investigators and subjects, the first NDA for tetumumab was accepted, which is also the first IGF-1R antibody drug in China to submit an NDA," he said. Tetumumab has demonstrated excellent and comprehensive efficacy benefits in pivotal registration studies, including alleviation of proptosis, control of disease activity, and improvement of quality of life. We will actively cooperate with the regulatory authorities and look forward to providing effective and safe treatment options for TED patients in China as soon as possible to meet this urgent clinical need." Innovent will continue to innovate in the therapeutic areas of oncology, autoimmunity, cardiovascular and metabolic (CVM) and ophthalmology to meet people's pursuit of a better life and serve more patients. "

About thyroid eye disease ( TED）

TED is an autoimmune disease affecting eye tissue, usually associated with toxic diffuse goiter (Graves' disease, GD), and is the most common orbit-related disease in adults. TED can be seen in about 25~50% of GD patients, but also in other thyroid diseases, even in patients with normal thyroid function [6].

The estimated annual incidence of TED is 16 per 100,000 women and 2.9 per 100,000 men [1], with a prevalence of 0.1 to 0.3% [2]. According to the severity of the disease, it can be divided into mild, moderate to severe and very severe. Although TED is more common in women, severe cases are more common in men. TED is most common in patients aged 30~50 years, and severe TED cases are more common in patients over 50 years of age [7]. At present, the pathogenesis of TED is not fully understood, but several studies have shown that OFs present in the connective tissue space of myofibers and orbital fibers are key factors in the hyperplasia of orbital soft tissue in TED [8].

The natural history of TED is divided into active and inactive phases [9]. The most common symptoms are dry eyes, ocular foreign body sensation, photophobia, lacrimation, diplopia, and postocular pressure, while typical signs include proptosis, upper eyelid retraction, eyelid edema, periorbital tissue, and bulbar conjunctival edema. TED is usually mild to moderate to severe, and about 3~5% of TED patients will develop to very severe, manifesting as vision-threatening corneal ulcers or compressive optic neuropathy [10]. In addition to the potential impact on appearance and visual function, TED has an extremely serious impact on patients' social functioning and quality of life.

At present, the first-line treatment for moderately to severely active TED is intravenous pulse glucocorticoid therapy, which has problems such as unsatisfactory improvement of exophthalmos and hormone-related systemic side effects, and there is still a large unmet clinical need. Second-line therapy includes a second dose of hormones or a combination of orbital radiation therapy or other immunomodulators. Biologics such as teprotumumab, tociizumab, and rituximab have also been recommended as second-line treatment options for moderately to severely active TED by EUGOGO guidelines [3], Chinese guidelines for the clinical diagnosis and treatment of thyroid eye disease (2022) [4], and the American Thyroid Society and European Thyroid Society Consensus on Thyroid Eye Diseases [5]. In particular, for TED with significant exophthalmos, IGF-1R-targeting tetumumab may be preferred.

About tetumumab ( IBI311)

Tetumumab 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 that plays a role in development, metabolism, and immune regulation, and is overexpressed in OFs, B cells, and T cells in TED patients [11]. Tetumumab can block the activation of IGF-1R signaling pathway 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 glycosaminoglycans caused by the activation of OFs, and alleviating inflammatory responses. Inhibition of the differentiation of OFs into adipocytes or myofibroblasts can reduce disease activity in TED patients and improve symptoms and signs such as proptosis, diplopia, and ocular congestion and edema.

In May 2024, the first NDA for tetumumab was accepted by the NMPA for the treatment of TED.

About Innovent Biologics:

It is the mission and goal of Innovent Biologics to develop high-quality biologics that people can afford. Founded in 2011, Innovent is committed to developing, manufacturing and marketing innovative drugs for major diseases such as oncology, metabolism and cardiovascular, autoimmune, and ophthalmology. The company has 10 products approved for marketing, 4 varieties are in the NMPA review, 4 new drug molecules have entered phase III or pivotal clinical studies, and 18 new drugs have entered clinical studies. The company has in-depth cooperation with domestic and foreign pharmaceutical companies to accelerate drug innovation, and has reached more than 30 strategic cooperation with international partners such as Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center.

While continuously developing innovative drugs and pursuing its own development, Innovent has always been scientifically benevolent, adheres to the "patient-centered" approach, cares about patients and their families, and actively fulfills its social responsibilities. Innovent hopes to work with you to improve the development of China's biopharmaceutical industry to meet the people's access to medicines and people's pursuit of good wishes for life and health.

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Disclaimer: Innovent does not recommend any unapproved drugs/indications.

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