Innovent Announces Primary Endpoint Met in the Phase 3 Clinical Trial (RESTORE-1) of IBI311 (Anti-IGF-1R Antibody) in Treating Thyroid Eye Disease and Plans to Submit NDA to the NMPA
ROCKVILLIE, MD. and
RESTORE-1 (CTR20223393) is a multicenter, randomized, double-masked, placebo-controlled Phase 2/3 clinical trial to evaluate the efficacy and safety of IBI311 in subjects with TED. The Phase 3 results of RESTORE-1 showed that the primary endpoint was successfully met: at Week 24, the proptosis responder rate in the study eye (the percentage of subjects with a reduction in proptosis of ≥2 mm from baseline in the study eye without deterioration ≥ 2 mm increase of proptosis in the fellow eye) was significantly higher in subjects treated with IBI311 than in subjects treated with placebo: 85.8% vs. 3.8%, with a difference of 81.9% (95% CI: 69.8% to 93.9%, P < 0.0001).
In addition, the key secondary endpoints of the study such as overall response rate(the percentage of subjects with a reduction in proptosis of ≥2 mm from baseline and improvement in clinical activity score ≥2 in the study eye), percentage of subjects with a clinical activity score (CAS) of 0 or 1, and mean change in proptosis from baseline in the study eye were successfully met: IBI311 significantly improved all the above parameters as compared to the placebo.
The overall safety profile of IBI311 was favorable throughout the study with no serious adverse events occurred. The efficacy and safety profiles in the Phase 3 part of the RESTORE-1 study were consistent with its Phase 2 results. Detailed results from the study will be released in medical conferences or journals in the future.
As an autoimmune disease involving ocular tissues, the annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men1,and the estimated prevalence of clinically relevant TED ranges from 0.1% to 0.3%2. At present, there is no targeted drug approved for the treatment of TED in
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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 euthyroidism6.
The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men1,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 years7. 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 TED8.
The natural history of TED is divided into active and inactive phases9. 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 neuropathy10. 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
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 patients11. 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 and other symptoms and signs.
About Innovent
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. 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, 3 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 19 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi,
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).
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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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