Innovent Biologics, Inc. recently announced that Sycume (IBI311) achieved the primary and key secondary endpoints in the phase 3 RESTORE-3 clinical trial in participants with inactive thyroid eye disease (TED).
Give me a refresher on Innovent.
The biopharmaceutical company was founded in 2011 and is headquartered in Suzhou, Jiangsu, China.
Its focus: Developing, manufacturing and commercializing high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases.
Moving on to Sycume.
The therapy: teprotumumab N01), a recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody.
What it does: blocks the activation of IGF-1R signaling pathway mediated by IGF-1 and related ligands or agonistic antibodies, reducing the expression of downstream inflammatory factors.
The intended treatment effect: to decrease the synthesis of hyaluronic acid and other glycosaminoglycans caused by orbital fibroblast (OF) activation, thereby alleviating inflammation and preventing OFs differentiation into adipocytes or myofibroblasts.
This in turn reduces disease activity and improves clinical manifestations such as:
- Proptosis
- Diplopia
- Orbital congestion and edema
And why target individuals with inactive TED?
These patients account for approximately two-thirds of the overall TED population.
So what’s Sycume’s regulatory status?
Sycume was approved by China’s NMPA in March 2025 for the treatment of TED, making it the first IGF-1R antibody approved in China and the second approved worldwide for TED, after TEPEZZA (teprotumumab-trbw, Amgen) in the United States.
Note: Sycume has the same amino acid sequence as TEPEZZA but uses a different formulation developed by Innovent—hence the name teprotumumab N01.
Give me a reminder of the other TED therapies in the mix.
- Approved drugs:
- Enspryng (satralizumab-mwge; Genentech): approved just last week as the first and only subcutaneous (SC) injector for at-home treatment of TED.
- TEPEZZA: Approved by the FDA in 2020 and currently being studied in a phase 3 trial evaluating it being administered as an SC injection
- LUMVOA (veligrotug-vvze, Viridian Therapeutics): Received FDA approval in June of this year
- Pipeline drugs:
Duly noted. So, is there any prior data on Sycume?
Indeed. A phase 2 study (NCT05795621), noted a favorable safety profile and significant efficacy signals, including a regression of exophthalmos and clinical activity score (CAS) improvement.
And more recently: Sycume also met the primary endpoint and key secondary endpoints in RESTORE-1, a multicenter, randomized, double-masked, placebo-controlled phase 2/3 trial (NCT05795621) evaluating the drug in active TED.
Tell me more about RESTORE-3.
The multicenter, randomized, double-blind, placebo-controlled phase 3 study (NCT07113262) is evaluating the efficacy and safety of Sycume (also known as IBI311) in Chinese participants with inactive TED.
The cohort: 116 participants with inactive TED (bilateral clinical activity score [CAS] ≤ 2 points) with an approximate 2:1 ratio to receive either Sycume or placebo.
Other details to note:
- Mean disease duration: 4.3 years
- Baseline mean proptosis distance in the study eye: 22.16 mm
- Percent of patients presenting with a baseline CAS of 0 or 1: 74.1%
The main outcome measures:
- Primary endpoint: Proptosis response rate of the study eye at Week 24
- Secondary endpoint: Change from baseline in proptosis of the study at Week 24
Findings?
Sycume achieved both the primary and secondary endpoints while demonstrating remarkable efficacy in reducing proptosis in participants with inactive TED:
- At Week 24, the proptosis response rate in the study eye was significantly higher in the Sycume group compared with the placebo group (60.4% vs. 23.5%; treatment difference: 36.9 percentage points; p = 0.0003)
- At Week 24, the least squares mean (LS mean) change from baseline in study eye proptosis distance in the Sycume group was -1.88 mm, demonstrating statistically significant superiority over placebo (-0.88 mm; treatment difference: -1.00 mm; p < 0.0001)
Did Sycume impact non-study eyes?
Indeed. At Week 24, the proptosis response rate (PRR) in non-study eyes was higher in the Sycume group than in the placebo group (46.0% vs. 19.8%; p = 0.0071).
- In fact: the LS mean change from baseline in proptosis distance in non-study eyes reached -1.77 mm in the Sycume group versus -0.91 mm in the placebo group (p < 0.0001), which was consistent with the trend observed in study eyes.
What about the safety data?
The drug also exhibited a favorable safety profile during the double-blind treatment and follow-up period, with most treatment-emergent adverse events being mild to moderate in severity.
Plus: no new safety signals were identified.
How did these findings compare to TEPEZZA?
While the baseline mean proptosis in RESTORE-3 was lower than that in the TEPEZZA study (indirect comparison from Innovent), the PRR and the proptosis reduction of Sycume were generally consistent with TEPEZZA's data in inactive TED.
Any comments from Innovent?
Per Zhongyan Shan, , lead principal investigator of the study: “Results from this trial confirm that Sycume yields robust and clinically meaningful reductions in proptosis even in patients with chronic, inactive TED.”
Shan, who is with the First Hospital of China Medical University, added that the data not only validates the therapeutic value of targeting IGF-1R in long-duration inactive TED, but “also offers tens of thousands of chronic TED sufferers and clinicians a novel non-surgical treatment paradigm—promising new hope and restored quality of life for patients with inactive TED.”
Last question: When can we expect an update from this study?
No specific timeline was provided.
However, Innovent noted that the follow-up of RESTORE-3 is still ongoing—and the complete data will be published in future academic conferences or peer-reviewed academic journals.