Innovent Biologics Announces IBI311 (Anti-IGF-1R Antibody) Meets Primary Endpoint in Phase III RESTORE-1 Trial for Thyroid Eye Disease and Plans NDA Submission

February 20, 2024, Rockville, USA and Suzhou, China – Innovent Biologics Group (HKEX Stock Code: 01801), a biopharmaceutical company dedicated to the research, development, production, and commercialization of innovative medicines for major diseases including oncology, autoimmunity, metabolism and cardiovascular disorders, and ophthalmology, today announced that its Phase III registrational clinical study (RESTORE-1) evaluating IBI311, a recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody injection (development code: IBI311), in subjects with thyroid eye disease (TED) in China has met its primary endpoint. Innovent plans to submit a New Drug Application (NDA) to the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for IBI311 for the treatment of TED.

RESTORE-1 (CTR20223393) is a multicenter, randomized, double-blind, placebo-controlled Phase II/III clinical study evaluating the efficacy and safety of IBI311 in subjects with thyroid eye disease (TED). The study results demonstrated that the primary endpoint of the Phase III stage of RESTORE-1 was successfully met: at Week 24, the proptosis response rate in the study eye among subjects treated with IBI311 was significantly superior to that in the placebo group. The proptosis response was defined as a reduction in proptosis of ≥2 mm from baseline in the study eye without an increase of ≥2 mm in proptosis in the fellow eye. The proptosis response rates in the study eye were 85.8% in the IBI311 group and 3.8% in the placebo group, with a between-group difference of 81.9% (95% CI: 69.8%–93.9%; P<0.0001).

Furthermore, key secondary endpoints of the study, such as the overall orbital response rate in the study eye (defined as the proportion of subjects with a reduction in proptosis of ≥2 mm from baseline and an improvement in Clinical Activity Score [CAS] of ≥2 points in the study eye), the percentage of subjects with a CAS of 0 or 1 in the study eye, and the change in proptosis of the study eye from baseline, were all successfully met. IBI311 demonstrated significantly greater improvement in these metrics compared to the placebo group.

Throughout the study period, IBI311 demonstrated a favorable overall safety profile, with no serious adverse events reported. The efficacy trends and safety characteristics observed in the Phase III stage of the RESTORE-1 study were highly consistent with those from the Phase II stage. Detailed study data will be further analyzed and presented at future academic conferences or published in academic journals.

As an autoimmune disease involving ocular tissues, the estimated annual incidence of TED is 16 per 100,000 in women and 2.9 per 100,000 in men.¹, with a prevalence of 0.1-0.3%². Currently, no targeted therapies for thyroid eye disease have been approved in China, whereas multiple clinical practice guidelines both domestically and internationally have included IGF-1R-targeting antibody biologics in their recommended treatment regimens.^3,4,5, particularly for TED with significant exophthalmos, IGF-1R-targeting antibody biologics may be considered the first-line treatment.

Professor Fan Xianqun, Academician of the Chinese Academy of Engineering, Chief Investigator of this clinical study, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine“Thyroid eye disease (TED) is one of the most common orbital disorders in adults. It is an organ-specific autoimmune disease closely associated with thyroid dysfunction, significantly impairing patients’ visual function and appearance. Currently, there are no approved targeted therapies for TED in China, and treatment options remain limited. As the principal investigator of the RESTORE-1 study, I am delighted to see that IBI311 has met its primary endpoint in the Phase III trial and demonstrated a favorable safety profile, further confirming the excellent therapeutic efficacy of IBI311. I look forward to sharing the detailed data from this high-quality study in the near future and wish it success in its marketing approval application, so as to bring benefit to Chinese patients with TED at an early date.”

Dr. Qian Lei, Vice President of Clinical Development at Innovent Bio, stated, “No targeted therapies have been approved for thyroid eye disease (TED) in China, while overseas drugs targeting the same mechanism are prohibitively expensive. Innovent Bio’s pipeline has always been guided by unmet medical needs. The company’s independently developed monoclonal antibody IBI311, which targets IGF-1R, demonstrated significant efficacy and a favorable safety profile in the RESTORE-1 study. We will submit a new drug application as soon as possible to break through the current limitations in clinical treatment options for TED, bringing high-quality, highly effective, and safe biologics to Chinese patients with TED. Meanwhile, with Xinbile^®(PCSK9 monoclonal antibody) has been approved for market launch, and the New Drug Application (NDA) for mazdutide (GLP-1R/GCGR) has been accepted. IBI311 has met its Phase III clinical trial endpoints. Innovent Bio’s strategic layout of innovative therapies in the fields of metabolism and cardiovascular (CVM), endocrinology, and ophthalmology is gradually entering a harvest period, with the potential to build a comprehensive product portfolio and long-term competitive advantages. We will continue to strive to meet people’s aspirations for a better life and serve more patients.”

Thyroid eye disease (TED) is an autoimmune disorder affecting ocular tissues, commonly associated with Graves’ disease (GD), and represents the most prevalent orbitopathy in adults. TED occurs in approximately 25–50% of patients with GD and may also be observed in individuals with other thyroid disorders or even those with euthyroid status.⁶。

The estimated annual incidence of TED is 16 per 100,000 individuals (female) and 2.9 per 100,000 individuals (male).¹, with a prevalence of 0.1-0.3%². Based on disease severity, it can be classified into mild, moderate-to-severe, and very severe forms. Although TED is more common in women, severe cases are more frequently observed in men. TED most commonly affects patients aged 30–50 years, whereas severe TED cases are more prevalent among patients over 50 years of age.⁷. Currently, the pathogenesis of TED is not fully understood; however, multiple studies have indicated that orbital fibroblasts (OFs) present in muscle fibers and the interstitial spaces of orbital fibrous connective tissue are key factors driving the proliferation of orbital soft tissues in TED.⁸。

The natural course of TED is divided into active and inactive phases.⁹. The most common symptoms are dry eyes, foreign body sensation, photophobia, tearing, diplopia, and retrobulbar pressure, while typical signs include exophthalmos, upper eyelid retraction, eyelid edema, and edema of the periorbital tissues and bulbar conjunctiva. TED is usually mild to moderately severe; approximately 3–5% of patients with TED progress to sight-threatening disease, manifesting as corneal ulceration or compressive optic neuropathy.¹⁰. In addition to potentially affecting appearance and visual function, TED has an extremely severe impact on patients' social functioning and quality of life.

Currently, the first-line treatment for moderate-to-severe active Thyroid Eye Disease (TED) is intravenous pulse glucocorticoid therapy. However, issues such as suboptimal improvement in proptosis and systemic side effects associated with glucocorticoids remain, indicating a significant unmet clinical need. Second-line treatments include repeat glucocorticoid pulse therapy, either alone or in combination with orbital radiotherapy or other immunomodulatory agents. Biologic agents such as teprotumumab, tocilizumab, and rituximab are also recommended by the EUGOGO guidelines.³《Chinese Guidelines for the Clinical Diagnosis and Treatment of Thyroid Eye Disease (2022)》⁴Consensus on Thyroid Eye Disease from the American Thyroid Association and the European Thyroid Association⁵It is recommended as a second-line treatment for moderate-to-severe active Thyroid Eye Disease (TED). Particularly for TED accompanied by significant proptosis, teprotumumab, an IGF-1R inhibitor, may be considered the preferred option.

IBI311 is a recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody developed by Innovent Bio 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 orbital fibroblasts (OFs), B cells, and T cells of patients with TED.¹¹IBI311 can block the activation of the 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 OFs activation, and alleviate inflammatory responses; it also inhibits the differentiation of OFs into adipocytes or myofibroblasts, thereby reducing disease activity in TED patients and improving symptoms and signs such as exophthalmos, diplopia, and ocular congestion and edema.

“Rooted in Trust, Realized through Action.” It is Innovent Bio’s mission and goal to develop high-quality biologics that are affordable for the general public. Founded in 2011, Innovent Bio is dedicated to the development, manufacturing, and commercialization of innovative medicines for major disease areas, including oncology, metabolism and cardiovascular diseases, autoimmune disorders, and ophthalmology. The company has obtained marketing approval for 10 products, with three additional products under review by the National Medical Products Administration (NMPA), four new drug molecules in Phase III or pivotal clinical studies, and another 19 new drug candidates in various stages of clinical development. By fostering in-depth collaborations with domestic and international pharmaceutical companies to accelerate drug innovation, Innovent Bio has established more than 30 strategic partnerships with global collaborators such as Eli Lilly, Roche, Sanofi, Adimab, Incyte, and the MD Anderson Cancer Center.

Innovent Bio, while continuously developing innovative drugs and pursuing its own growth, has always upheld a spirit of scientific benevolence, adhering to a “patient-centric” philosophy. By caring for patients and their families, the company actively fulfills its social responsibilities. Innovent Bio is committed to working collaboratively with all stakeholders to elevate the development level of China’s biopharmaceutical industry, thereby improving medication accessibility for the public and fulfilling people’s aspirations for better health and well-being.

Disclaimer: Innovent Bio does not recommend the use of any unapproved drugs or indications.

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