Biosimilar Agent Promising as a Newer Alternative for TED Treatment

In East Asian patients, TED-related proptosis tends to be less detectable and compressive optic neuropathy may occur earlier in the disease course, often with less obvious periorbital inflammation. As well, white populations typically experience more inferior rectus muscle involvement, while Asians experience observable medial rectus enlargement first, in turn creating different patterns of strabismus and diplopia. These images (not from the study) show a TED patient before (top) and after (bottom) therapy. Photo:  Bobby Saenz, OD. Click image to enlarge. Thyroid eye disease (TED) has traditionally relied on control strategies of high-dose corticosteroids, orbital radiation and multistage surgical intervention. However, these options are limited in their significant morbidity, delayed functional recovery and variable efficacy. The inception of teprotumumab changed the landscape for TED, offering the first targeted medical therapy possible of reversing tissue expansion and restoring function. Since then, the RESTORE-1 study was conducted and used IBI311, a biosimilar of teprotumumab, which is an insulin-like growth factor 1 receptor (IGF-1R) inhibitor.The RESTORE-1 study was a randomized, double-masked, placebo-controlled, Phase III multicenter clinical trial that extended over 24 weeks and was conducted across 20 tertiary hospitals in China. Those with active moderate to severe TED were included (clinical activity score [CAS] ≥3) and exclusions were those with active TED onset over 270 days, sight-threatening TED or history of steroid pulse therapy, radiotherapy or surgery for the condition.After 82 participants were randomized 2:1 to receive intravitreous IBI311 infusions or placebo, they were injected once every three weeks for 21 weeks and follow-up extending through 24 weeks. At week 24, 85.8% of those receiving the drug had proptosis response, compared with only 3.8% of the placebo. Overall reduction (proptosis reduction ≥2mm and CAS reduction ≥ 2) was unsurprisingly also much better in the drug group, being 80.2% vs. 3.6%, respectively. CAS of zero or one similarly made up 83.5% of the drug group and 16.6% of the placebo and diplopia response (diplopia reduction ≥1 grade) occurred in 66.0% vs. 53.3%, respectively. All adverse events—including infusion reaction, hearing impairment, hyperglycemia, muscle spasm and nausea or diarrhea—were mild or moderate.The authors of the JAMA Ophthalmology paper elaborate on their findings, noting that rapid effects with IBI311 were observable at week six with continued improvement, culminating in more prominent differences at week 24. Proptosis change at this final week appeared to be similar to results of the Phase III clinical trials for teprotumumab and orbital decompression surgery. Although the safety profile of IBI311 is somewhat comparable to teprotumumab, it was found to have higher incidences of hearing impairment and menstrual disorder.Despite these effects, the authors conclude that “IBI311 improved quality of life and demonstrated no new safety issues not identified in previous clinical trials, suggesting the potential of IBI311 as a novel treatment option for TED.”1 More specifically, they believe “the results suggest that IBI311 represents a viable treatment option for Chinese patients with active TED.”1In an invited commentary also published in JAMA Ophthalmology, two authors point out that one of this study’s main strengths lies in its population of exclusively East Asians, since IGF-1R inhibitor treatment was mainly established through studies of white individuals. The underrepresentation was a major limitation, since clinical TED manifestations vary widely by ethnicity. However, in the demonstration of robust response in Chinese patients, this study confirms the IGF-1R inhibitor is effective despite anatomical and clinical variations.The commentators do add, however, that limitations of this study should not be ignored. They draw attention to the small number of participants, inhibiting them from confidently stating whether there was or was not a difference in changes in diplopia between groups. What’s more, none of the cases included had compressive optic neuropathy, so conclusions can’t be well made about efficacy in severe and vision-threatening cases. They also add that hearing-related adverse events occurred in 20.4%, which should prompt further investigation.Although these shortcomings need to be addressed, the commentators still advocate that “the development of biosimilar agents, such as IBI311, offers a promising avenue for expanding treatment access. With similar efficacy and potentially reduced cost, biosimilars may play a critical role in making biologic therapy more accessible to a broader population, especially in resource-limited settings.”2Click here for the journal source and here for the commentary. 1. Zhang H, Sun J, Li Y, et al. IGF-1R inhibitor IBI311 for the treatment of active thyroid eye disease in Chinese patients: the RESTORE-1 randomized clinical trial. JAMA Ophthalmol. October 9, 2025. [Epub ahead of print].2. Vloka C, Liao SD. Expanding the potential treatment of thyroid eye disease. JAMA Ophthalmol. October 9, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.