Phase III Study for New TED Drug Demonstrates Positive Effects

A 2mm reduction of proptosis is considered to be a clinically meaningful outcome for patients because it is expected to reduce the incidence of diplopia and improve the lid coverage over the cornea and is associated with improvements in quality of life. Photo: Bobby Saenz, OD. Click image to enlarge. Pharmaceutical treatment options for thyroid eye disease (TED) have been somewhat limited historically, although the FDA approval of Tepezza (teprotumumab-trbw) in 2020 offered a new avenue to clinical improvement that proved successful in many cases. Recently, a global multicenter Phase III trial called THRIVE was initiated to assess a 10mg/kg dose of veligrotug, an investigational drug candidate, over 12 weeks. The drug is administered as five intravenous (IV) infusions. Veligrotug has received breakthrough therapy designation from the FDA for the treatment of TED, suggesting that it may offer substantial clinical benefit over current therapies.A recent paper published in Ophthalmology presented efficacy and safety outcomes from the THRIVE trial, which evaluated veligrotug in patients with moderate-to-severe active TED. The researchers determined that the drug demonstrated rapid, robust and statistically significant improvements in major clinical domains, and these improvements were accompanied by corresponding clinically meaningful improvements in quality of life.A total of 113 patients received veligrotug (n=75) or placebo (n=38) every three weeks for a total of five IV infusions. The primary endpoint at week 15 was the proptosis responder rate ( ≥2mm reduction by Hertel exophthalmometry) or overall responder rate (proptosis responder rate and ≥ two-point reduction in clinical activity score), depending on geographic region.Improvements were observed at week three, with a significantly greater response at week 15 for veligrotug vs. placebo across all primary and secondary endpoints, including proptosis responder rate by Hertel: 70% vs. 5%; proptosis responder rate by MRI or CT: 71% vs. 9%; overall responder rate: 67% vs. 5%; mean proptosis reduction: 2.90mm vs. 0.48mm (Hertel) and 2.96mm vs. 0.58mm (MRI/CT); diplopia improvement: 59% vs. 20%; and diplopia resolution: 49% vs. 12%.At week 52, 70% of initial responders maintained a proptosis response. Veligrotug was generally well tolerated, with a 4% treatment discontinuation rate. Most adverse events were mild and resolved, with no serious treatment-related adverse events and no changes in the safety profile through week 52.The researchers noted in their paper that “improvements in both proptosis and diplopia at this early time point suggest that veligrotug’s full antagonism of the IGF-1R pathway may quickly disrupt the thyroid-stimulating hormone receptor–IGF-1R complex signaling pathway that drives TED pathologic characteristics.”Among the proptosis responders at week 15, the mean reduction was 3.7mm, a substantial result achieved through nonsurgical treatment.The research team highlighted that their study was the first TED trial to incorporate MRI/CT imaging in the study protocol globally, enabling an objective assessment of proptosis. The MRI/CT proptosis measurements demonstrated a high level of concordance with traditional Hertel exophthalmometry in THRIVE.“These results support veligrotug’s potential to advance TED management by offering a next-generation therapy that targets the underlying pathophysiologic features and its clinical manifestations,” they concluded.Click here for the journal source.  Yen MT, Cockerham K, Saeed P, et al.; THRIVE Study Group. A Phase III, randomized, double-masked, placebo-controlled study of veligrotug for active thyroid eye disease. Ophthalmology. June 1, 2026. [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.