Key Takeaways

  • Patients treated with the investigational IGF-1R antibody veligrotug achieved significantly greater improvements in active thyroid eye disease compared with placebo in the phase 3 THRIVE trial
  • Veligrotug demonstrated clinically meaningful benefits across key measures of disease activity, supporting IGF-1R inhibition as an effective targeted treatment strategy for TED
  • The FDA granted the application Priority Review and set a Prescription Drug User Fee Act (PDUFA) target action date of June 30, 2026 for the treatment

A novel biologic therapy may expand treatment options for patients with thyroid eye disease (TED), according to results from the phase 3 THRIVE trial published in Ophthalmology.1

Researchers reported that Viridian Therapeutics' veligrotug, a fully antagonistic monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), demonstrated significant efficacy and a favorable safety profile in patients with active TED. 

The THRIVE trial was designed to evaluate whether blocking IGF-1R signaling with veligrotug could reduce the inflammatory and tissue-remodeling processes that drive TED. Investigators assessed both efficacy and safety outcomes in patients with active disease.

In the trial, adult patients with moderate-to-severe active TED (onset ≤ 15 months, proptosis ≥ 3 mm above normal, and clinical activity score [CAS] ≥ 3) were randomized 2:1 to receive 10 mg/kg veligrotug or placebo administered every 3 weeks for a total of 5 IV infusions. A total of 113 patients received veligrotug (n = 75) or placebo (n = 38).

Improvements were observed at week 3, with a significantly greater response at week 15 for veligrotug versus placebo (P < 0.001) across all primary and secondary end points including: PRR by Hertel, 70% versus 5%; PRR by magnetic resonance imaging (MRI) or computed tomography (CT), 71% versus 9%; ORR, 67% versus 5%; mean proptosis reduction, 2.90 mm versus 0.48 mm (Hertel) and 2.96 mm versus 0.58 mm (MRI/CT); diplopia improvement, 59% versus 20%; and diplopia resolution, 49% versus 12%. At week 52, 70% of initial responders maintained 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.

According to the researchers, the results reinforce growing evidence that IGF-1R plays a central role in the pathophysiology of thyroid eye disease. By directly targeting this pathway, veligrotug may help address the underlying mechanisms driving inflammation, tissue expansion, and orbital changes associated with TED.

In December, Viridian announced that the FDA has accepted the Biologics License Application (BLA) for veligrotug for the treatment of TED. The FDA granted the application Priority Review and set a Prescription Drug User Fee Act (PDUFA) target action date of June 30, 2026.

Reference

1. Yen MT, Cockerham K, Saaed P, et al; THRIVE Study Group. THRIVE: a phase 3, randomized, double-masked, placebo-controlled trial of veligrotug in active thyroid eye disease. Ophthalmology. 2026. doi:10.1016/j.ophtha.2026.04.025.