Innovent Announces the New Drug Application of IBI311 (IGF-1R antibody) has been Accepted by the NMPA of China for Thyroid Eye Disease

Rhea-AI Summary

Innovent Biologics announced that the New Drug Application (NDA) for their recombinant anti-IGF-1R antibody, IBI311, has been accepted and given priority review by the China National Drug Administration for treating Thyroid Eye Disease (TED). This marks the first submission of an anti-IGF-1R antibody in China. The NDA acceptance is based on positive results from the Phase 3 RESTORE-1 trial, which showed significant improvements in proptosis, disease activity, and quality of life with a favorable safety profile. Detailed results will be presented in 2024. TED, an autoimmune disease affecting eye tissues, lacks effective treatment options in China, making IBI311's approval potentially impactful for patients. Innovent is enhancing its portfolio in ophthalmology, autoimmunity, and other major diseases.

Positive

• NDA for IBI311 accepted and granted priority review by the China National Drug Administration.
• First anti-IGF-1R antibody submission in China.
• Positive results from the Phase 3 RESTORE-1 trial: significant improvements in proptosis, disease activity, and quality of life.
• Favorable safety profile with no new safety signals identified.
• Potentially addresses over 60 years of lack of innovative TED treatments in China.
• Innovent is expanding its portfolio in ophthalmology, autoimmunity, and other major diseases.

Negative

• Pending NDA approval, the current use of IBI311 is to clinical trials.
• No detailed results from RESTORE-1 study available until 2024, creating a knowledge gap for investors.
• Dependence on regulatory approval, which can be uncertain and time-consuming.

SAN FRANCISCO and SUZHOU, China, May 20, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune, ophthalmology and other major diseases, today announced that the New Drug Application (NDA) for IBI311, a recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody, has been accepted and granted priority review designation by the Center for Drug Evaluation (CDE) of the China National Drug Administration (NMPA) for the treatment of Thyroid Eye Disease (TED). IBI311 is the first anti-IGF-1R antibody with NDA submitted in China. As a biological drug with a novel mechanism of action, IBI311 will potentially resolve an over 60-years shortage of innovative TED drugs in China by offering an effective, safe and accessible treatment option for Chinese TED patients.

This NDA was accepted based on the positive results of a Phase 3 registration clinical study RESTORE-1 (CTR20223393) in subjects with TED in China. The primary endpoint of the study was successfully met in February 2024. Significant improvements in proptosis, disease activity, and quality of life were observed in the IBI311 group compared to placebo. The overall safety profile of IBI311 was favorable, and no new safety signals were identified. Detailed results of the RESTORE-1 study will be presented at medical conferences or journals in 2024.https://www.prnasia.com/story/436967-1.shtml

TED is an autoimmune disease that causes progressive inflammation and damage to tissues around the eyes. The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men ^[1], with the estimated prevalence of 0.1-0.3%^[2].The use of IGF-1R-targeted antibody has been recommended in multiple clinical treatment guidelines worldwide^{[3, 4, 5]}; particularly, IGF-1R-targeted antibody is recommended as first-line therapy for patients with clinically significant proptosis. In China, there exists an urgent need for effective, safe and accessible treatment options.

Professor Xianqun Fan, an academician of the Chinese Academy of Engineering and the leading principal investigator of the study, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, stated, "TED is one of the most common orbital diseases in adults, with proptosis as the most apparent clinical manifestation. The course of TED is protracted, which seriously impairs patients' visual function and appearance, and usually brings a heavy psychological burden to patients. In China, physicians are hampered with limited choice of treatment. IBI311 has shown encouraging efficacy with respect to proptosis and orbital soft tissue inflammation with good safety in clinical studies. As the principal investigator of the RESTORE-1 study, I am proud of the NDA submission based on IBI311's promising efficacy and safety demonstrated in the pivotal study and would like to thank the effort of all investigators from participating sites. We look forward to the approval of IBI311, which will be a great advance in the management of TED and benefit more Chinese patients."

Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated, "We are honored to receive the regulatory acceptance of NDA for IBI311 with the support and dedication of participants, investigators and regulatory authorities. IBI311 has demonstrated favorable safety and comprehensive efficacy benefits in the RESTORE-1 study, including relief of proptosis, control of disease activity, and improvement in quality of life. We will actively communicate with the regulatory authorities during the NDA review and hope to provide an effective, safe and more accessible treatment option for Chinese TED patients as soon as possible. Innovent is strategically establishing its innovative commercial and late-stage portfolio in the fields of ophthalmology, autoimmunity, cardiovascular and metabolic (CVM) , aiming to help more people pursue a healthy life."

About Thyroid Eye Disease (TED)

TED 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. TED occurs in approximately 25 to 50% of GD patients and can also be seen in other thyroid diseases, even in euthyroidism^[6].

The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men^[1]，and the estimated prevalence of clinically relevant TED ranges from 0.1% to 0.3%^[2]. According to disease severity, it can be divided into mild, moderate and severe. Although TED 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 years^[7]. At present, the pathogenesis of TED is not fully understood, but several studies have shown that orbital fibrous present in muscle fibers, orbital fibrous connective tissue space are key factors leading to orbital soft tissue enlargement in TED^[8].

The natural history of TED is divided into active and inactive phases^[9]. The most common symptoms are dry eye, ocular gritty, photophobia, lacrimation, diplopia, and pressure behind the eye, while typical signs include upper eyelid retraction, eyelid edema, periorbital and conjunctival edema, and proptosis. TED is usually mild to moderate, and about 3–5% of patients with TED are severe, manifesting as severe pain, vision-threatening corneal ulcers, or compressive optic neuropathy^[10]. In addition to potentially affecting vision, TED can have an extremely severe impact on the patient's appearance and social functioning and quality of life.

Currently, the first-line treatment option for moderately severe active TED 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, Tocilizumab and Rituximab are recommended by the Chinese Clinical Diagnosis and Treatment Guidelines for Thyroid Eye Disease (2022)^[3], the European Group on Graves' orbitopathy (EUGOGO)^[4] and the consensus on thyroid eye disease of the American Thyroid Society and the European Thyroid Society^[5] as the second-line treatment options for moderate to severe active TED. Teprotumumab targeting IGF-1R is recommended as first-line therapy for patients with clinically significant proptosis.

About IBI311

IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent for the treatment of TED. IGF-1R is a transmembrane tyrosine kinase receptor that plays a role in the development, metabolism, and immune regulation, and is overexpressed in OFs, B, and T cells of TED patients^[11]. 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 TED and improving proptosis, diplopia, ocular congestion and edema among other symptoms and signs. 

In May 2024, the NDA for IBI311 was accepted by the NMPA for the treatment of TED.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable illnesses. Its pioneering therapies to treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 4 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).

Forward-looking statement

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or is otherwise inaccurate.

 

References

1.       Li Z, Cestari D M, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018; 29 (6): 528-534.

2.       Bartley G. The epidemiological characteristics and clinical course of ophthalmology associated with autoimmune thyroid disease in Olmsted Country, Minnesota. Trans Am Ophthalmol Soc 1994; 92: 477-588.

3.       Hiromatsu Y, Eguchi H, Tani J, Kasaoka M, Teshima Y. Graves' ophthalmopathy: epidemiology and natural history. Intern Med. 2014; 53 (5): 353-60.

4.       Edsel I. Thyroid Associated Orbitopathy. Retrieved June 7, 2011, from Medscape Reference: http://emedicine.medscape.com/article/1218444-overview # a1http://emedicine.medscape.com/article/1218444-overview

5.       Ali F, Chorsiya A, Anjum V, Ali A. Teprotumumab (TEPEZZA): From the Discovery and Development of Medicines to USFDA Approvals for Active Thyroid Eye Disease (TED) Treatment. Int Ophthalmol. 2021; 41 (4): 1549-1561.

6.       Dolman P J. Evaluating Graves' orbitopathy. Best Pract Res Clin Endocrinol Metab. 2012; 26 (3): 229-248.

7.       Bahn R S. Graves' ophthalmopathy. N Engl J Med. 2010; 362 (8): 726-738.

8.       Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' Orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' Orbitopathy. Eur J Endocrinol. 2021; 185 (4): G43-G67.

9.       Group of Oculoplastic and Orbital Diseases, Chinese Ophthalmology Branch, Chinese Medical Association; Group of Thyroid Diseases, Chinese Endocrinology Branch, Chinese Medical Association. Chinese Guidelines for the Diagnosis and Treatment of Thyroid Associated Ophthalmopathy (2022). Chinese Journal of Ophthalmology. 2022; 58 (9).

10.   Burch HB, et al. Management of Thyroid Eye Disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. Eur Thyroid J. 2022; 11 (6): e220189.

11.   Douglas RS, Naik V, Hwang CJ, et al. B cells from patients with Graves' disease erase express the IGF-1 receptor: implications for disease pathogenesis. J Immunol 2008; 181: 5768-5774.

 

 

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SOURCE Innovent Biologics

FAQ

What is the significance of the NDA acceptance for IBI311?

The NDA acceptance for IBI311, granted priority review by the China National Drug Administration, is significant as it is the first anti-IGF-1R antibody submission in China, aimed at treating Thyroid Eye Disease (TED).

What were the results of the Phase 3 RESTORE-1 trial for IBI311?

The Phase 3 RESTORE-1 trial showed significant improvements in proptosis, disease activity, and quality of life in TED patients and a favorable safety profile with no new safety signals.

When will detailed results of the RESTORE-1 study be available?

Detailed results of the RESTORE-1 study are expected to be presented at medical conferences or in journals in 2024.

Why is IBI311 important for TED patients in China?

IBI311 is important for TED patients in China as it potentially offers an effective, safe, and accessible treatment option, addressing a significant unmet medical need.

What other fields is Innovent Biologics expanding its portfolio in?

Innovent Biologics is expanding its portfolio in ophthalmology, autoimmunity, cardiovascular, and metabolic diseases.