Veligrotug-vvze is the first FDA-approved thyroid eye disease treatment with data in both active and chronic disease.
The FDA has approved veligrotug-vvze (Lumvoa; Viridian Therapeutics) for the treatment of thyroid eye disease (TED), regardless of disease activity or duration. The approval, announced June 26, 2026, makes veligrotug the first TED therapy with labeling that includes clinical data in both active and chronic disease and the first approved product in this class to demonstrate a statistically significant effect on both diplopia response and complete diplopia resolution across the full disease spectrum.1
TED is a rare autoimmune condition most commonly associated with Graves disease, in which immune-mediated orbital inflammation and tissue remodeling produce proptosis, diplopia, periorbital edema, eyelid retraction, pain, and, in severe cases, vision loss. Approximately 40% of patients with Graves disease report clinical signs and symptoms of TED. Although the pathophysiology is not fully understood, autoantibodies that activate a signaling complex involving the thyrotropin receptor and the insulin-like growth factor-1 receptor (IGF-1R) appear to drive orbital fibroblast overexpression of IGF-1R, a hallmark of the disease, triggering the inflammatory cascade responsible for tissue expansion.1,2
Veligrotug is a full antagonist humanized monoclonal antibody antagonist targeting IGF-1R, designed to provide more complete inhibition of both proximal and distal IGF-1R signaling than partial antagonists. It is administered as 5 intravenous infusions of 10 mg/kg every 3 weeks over a 12-week course—a shorter regimen than the 8-infusion, 21-week schedule of the previously approved IGF-1R partial antagonist teprotumumab (Tepezza; Amgen). The FDA granted veligrotug a breakthrough therapy designation and priority review.1
The approval was supported by pivotal phase 3 trials. THRIVE (NCT05176639) was a global, multicenter, randomized, double-masked, placebo-controlled trial enrolling 113 adults with moderate-to-severe active TED (disease onset of ≤15 months, proptosis of 3 mm above normal or higher, clinical activity score [CAS] of ≥3) across 29 sites in North America, Europe, and Australia. Patients were randomly assigned 2:1 to receive veligrotug (n = 75) or placebo (n = 38).2,3
Trial Name: A Safety, Tolerability and Efficacy Study of Veligrotug (VRDN 001) in Healthy Volunteers and Participants With Thyroid Eye Disease (TED) (THRIVE)
ClinicalTrials.gov ID: NCT05176639
Sponsor: Viridian Therapeutics, Inc
Completion Date: March 27, 2025
At the week 15 primary analysis, veligrotug achieved statistically significant improvements across all primary and secondary end points vs placebo (all P < .001). The proptosis responder rate (PRR)—defined as a 2-mm or greater reduction from baseline by Hertel exophthalmometry—was approximately 70% with veligrotug vs 5% with placebo, with concordant results by MRI/CT (71% vs 9%). Mean proptosis reduction was about 2.90 mm vs 0.48 mm by the Hertel.2
Among patients with diplopia at baseline, 59% achieved improvement and 49% achieved complete resolution with veligrotug, compared with 20% and 12% with placebo, respectively. Disease inactivation, defined as a CAS of 0 or 1, was achieved in 65% of patients receiving veligrotug vs 18% receiving placebo.2
Importantly, improvements were observed as early as week 3, after a single infusion, with a median time to proptosis response of 3.5 weeks. Quality-of-life scores on the Graves' Ophthalmopathy Quality of Life questionnaire exceeded twice the 8-point minimally important difference threshold by week 15. Among week-15 proptosis responders with available follow-up data at week 52, approximately 70% maintained their response without new proptosis above baseline.2
THRIVE-2 (NCT06021054) enrolled 188 adults with moderate-to-severe chronic TED (disease onset greater than 15 months, proptosis of ≥3 mm, any CAS), randomly assigned 2:1 to veligrotug (n = 125) or placebo (n = 63) under the same 5-infusion dosing regimen. At week 15, the PRR was approximately 56% with veligrotug vs 8% with placebo (P < .0001), with a mean proptosis reduction of about 2.34 mm vs 0.46 mm. The overall responder rate was 56% vs 7% (P < .0001). Among patients with diplopia at baseline, the diplopia responder rate was 56% vs 25% (P = .0006), and complete resolution was achieved in 32% vs 14% (P = .0152).4,5
THRIVE-2 represents the first randomized controlled trial in chronic TED to demonstrate statistically significant improvements in both proptosis and diplopia.4,5
Across both trials, the most common adverse reactions (incidence of ≥5%) included muscle spasms, headache, hearing impairment, hyperglycemia, fatigue, diarrhea, ear discomfort, infusion-related reactions, nausea, nasopharyngitis, elevated creatine phosphokinase, dry skin, and hypertension. Infusion-related reactions occurred in approximately 9% of patients and were generally mild to moderate. These were manageable with corticosteroids, antihistamines, and antipyretics or infusion rate adjustments.1
“The hyperglycemia observed during treatment with Lumvoa is expected to be transient, and blood glucose levels should return to the patient’s baseline when treatment is completed or discontinued,” Michael Yen, MD, professor of oculoplastic surgery and ophthalmology at Baylor College of Medicine and THRIVE investigator, said in an interview. “Some patients may require adjustments to their diabetes medications if significant hyperglycemia is observed.”
Pharmacists should be aware of several labeled warnings. Hyperglycemia was reported in 15% of patients receiving veligrotug in THRIVE, with approximately half having preexisting diabetes or impaired glucose tolerance; blood glucose should be assessed before each infusion and monitored throughout treatment. Hearing impairment, which may be permanent in some cases, warrants audiologic assessment before, during, and after treatment. Prescribers should also monitor patients for signs and symptoms of inflammatory bowel disease, and discontinuation is warranted if it is suspected. Females of reproductive potential should use contraception during treatment and for 6 months following the last dose.1,2
“Some patients with longstanding, apparently quiescent, thyroid eye disease have had significant and meaningful responses to treatment with [veligrotug],” Yen explained. “Patients should be advised to see their physician for evaluation to determine if treatment with [veligrotug] is appropriate.”
Viridian has announced immediate commercial availability of veligrotug, supported by the ViridianCares patient support program, which provides insurance benefit verification, patient access liaisons, and financial assistance for eligible patients.1
