Innovent reports that SYCUME (IBI311) met the Phase 3 RESTORE-3 endpoint, improving proptosis versus placebo in inactive thyroid eye disease.
Written By: Neha Vishwakarma, PharmD
Reviewed By: Pharmacally Editorial Team
Innovent Biologics announced on October 8, 2026, that SYCUME® (teprotumumab N01 injection; IBI311) met the primary endpoint in RESTORE-3, a Phase 3 trial evaluating the drug in Chinese patients with inactive thyroid eye disease (TED). The multicenter, randomized, double-blind, placebo-controlled study demonstrated a significantly higher proptosis response rate with IBI311 than with placebo at Week 24.
SYCUME is a recombinant monoclonal antibody targeting the insulin-like growth factor 1 receptor (IGF-1R). It was approved in China for TED in March 2025 and subsequently included in the country’s National Reimbursement Drug List (NRDL), effective January 1, 2026. The RESTORE-3 findings extend the company’s clinical evaluation of IBI311 to patients with inactive disease.
Understanding Inactive Thyroid Eye Disease
TED is an autoimmune condition affecting the tissues surrounding the eyes and is commonly associated with Graves’ disease. Clinical manifestations include proptosis, eyelid retraction, swelling, double vision, light sensitivity and discomfort or pressure around the eyes. A small proportion of patients develop sight-threatening complications.
The disease generally progresses through active and inactive stages. Inactive TED may persist after the inflammatory phase has subsided, leaving patients with residual proptosis, double vision or other structural changes. Management may include orbital decompression, strabismus surgery or eyelid reconstruction, depending on the manifestations and clinical needs.
RESTORE-3 investigated whether IBI311 could improve proptosis in patients whose disease had reached the inactive stage, addressing a population with persistent manifestations that may remain after active inflammation has diminished.
RESTORE-3 Trial Design and Patient Characteristics
The Phase 3 study enrolled 116 participants with inactive TED, defined by a bilateral Clinical Activity Score (CAS) of 2 or less. Participants were randomized in an approximately 2:1 ratio to receive IBI311 or placebo.
At baseline, the mean duration of TED was 4.3 years, and mean proptosis in the study eye was 22.16 mm. Approximately 74.1% of participants had a baseline CAS of 0 or 1, indicating low clinical inflammatory activity.
The primary endpoint was the proptosis response rate in the study eye at Week 24. The key secondary endpoint was the change from baseline in study-eye proptosis at the same time point.
IBI311 Improves Proptosis at Week 24
IBI311 met the primary endpoint, with a proptosis response rate of 60.4%, compared with 23.5% for placebo. The treatment difference was 36.9 percentage points (p = 0.0003).
The key secondary endpoint also favored IBI311. Least-squares mean proptosis change in the study eye was −1.88 mm with IBI311 and −0.88 mm with placebo, representing a between-group difference of −1.00 mm (p < 0.0001).
The company also reported improvements in the non-study eye. The proptosis response rate was 46.0% with IBI311 versus 19.8% with placebo (p = 0.0071). Mean proptosis change in the non-study eye was −1.77 mm and −0.91 mm, respectively (p < 0.0001).
These findings demonstrate a statistically significant treatment effect across the reported proptosis measures. However, the placebo response rate of 23.5% in the study eye highlights the importance of the controlled comparison when interpreting outcomes in patients with chronic, inactive disease. The clinical relevance of the mean between-group difference should be considered alongside the study’s responder criteria and additional patient-level outcomes.
Safety and Tolerability
Innovent reported that IBI311 had a favorable safety and tolerability profile during the double-blind treatment and follow-up period. Most treatment-emergent adverse events were mild to moderate, and no new safety signals were identified.
The announcement did not provide event-specific adverse-event rates or a detailed breakdown of individual safety outcomes. Consequently, the available results do not establish the frequency of specific adverse events in RESTORE-3. Longer-term safety assessment remains important as follow-up continues.
Comparison With TEPEZZA Requires Caution
Innovent stated that the inactive-TED efficacy results were generally consistent with published data for TEPEZZA® (teprotumumab), based on an indirect comparison. The company also noted differences in baseline proptosis between RESTORE-3 and the TEPEZZA study.
These findings should not be interpreted as evidence of equivalence or noninferiority. Differences in trial populations, baseline characteristics and study methods can influence cross-trial comparisons, and no head-to-head results were reported in the announcement.
SYCUME’s inclusion in China’s NRDL represents a reimbursement milestone that may support access for eligible patients. However, the extent of any access or cost advantage depends on individual reimbursement arrangements and other healthcare-system factors.
Regulatory Context and Remaining Questions
SYCUME received NMPA approval for TED in March 2025 and entered China’s NRDL effective January 1, 2026. RESTORE-3 adds evidence for IBI311 in inactive TED, but the announcement does not establish that the approved indication has been expanded.
The findings remain subject to several limitations. The trial enrolled Chinese participants, and the full dataset has not yet been published. Only Week 24 efficacy results were reported in the announcement, leaving the durability of response, outcomes after treatment and longer-term safety to be clarified.
Further analysis of the complete study results will help determine how these findings inform treatment decisions for patients with persistent manifestations of inactive TED.
References
Innovent Biologics. “Innovent Announces Phase 3 RESTORE-3 Study of SYCUME® (Teprotumumab N01 Injection) Met Primary Endpoint in Inactive Thyroid Eye Disease.” October 8, 2026
A Clinical Study to Evaluate the Efficacy and Safety of IBI311 in Subjects with Inactive Thyroid Eye Disease, ClinicalTrials.gov ID NCT07113262
About the Writer
Neha Vishwakarma (LinkedIn) is a Pharm.D professional with experience in clinical pharmacy, pharmacovigilance, and clinical research. She has hands-on experience in ADR assessment, ICSR processing, medication safety, and clinical data evaluation. Her research background in surgical site infections and antibiotic use supports her focus on evidence-based healthcare writing.