VRDN-001 Demonstrates Quick Response in Thyroid Eye Disease Trial

VRDN-001, a thyroid eye disease (TED) therapy currently under review, can elicit a rapid and sustained increases in insulin-like growth factor-1 (IGF-1) serum levels in both healthy volunteers and patients with TED when administered intravenously, according to a poster presented at the North American Neuro-Ophthalmology Society’s 49th annual meeting in Orlando, FL, help March 11-16, 2023.¹ The research shows the therapy’s clinically meaningful effect proptosis, inflammation, and diplopia at 6 weeks, following 2 infusions of 3, 10, or 20 mg/kg of VRDN-001.¹

The researchers randomly assigned participants to receive 2 intravenous infusions 3 weeks apart of either placebo or VRDN-001. Participants included 13 healthy volunteers (mean age, 49 [range: 25 to 73] years; 8 men, 5 women; placebo [n=3], 3 mg/kg [n=3], 10 mg/kg [n=3], or 20 mg/kg [n=4]) and 8 patients with TED (mean age, 41 [range: 27 to 59] years, 3 men, 5 women; placebo (n=2) or 10 mg/kg of VRDN-001 [n=6]). The investigators assessed the IGF-1 serum levels for 50 days.¹ 

All patients injected with any dose of VRDN-001 demonstrated rapid, sustained, and similar increases in IGF-1 serum levels. These serum increases all occurred within 1 day of treatment and were sustained for 50 days. For the healthy volunteer participants, mean IGF-1 serum levels increased within a day of the first infusion, reaching 3- to 5-fold above baseline, and continued to increase following a second infusion, eventually reaching 5- to 7-fold above the baseline.¹ 

In the patients with TED, mean IGF-1 serum levels increased from 139 ng/mL at baseline to 853 ng/mL after 2 infusions, representing a 6-fold increase. 

No increases in IGF-1 serum levels occurred for placebo-treated participants in either group.¹

“In TED patients, rapid and clinically meaningful improvement was seen in proptosis, inflammation, and diplopia at 6 weeks,” according to the presenters.

VRDN-001, an antagonist antibody to IGF-1 receptors, has a distinct mutational signature and a more complete antagonism of IGF-1 mediated signaling, as well as different binding and functional antagonism characteristics when compared with teprotumumab, according to a second poster presented at the conference.² That poster explains that VRDN-001 has a similar binding site to teprotumumab, but does not exhibit sensitivity to certain mutations in the IGF-1 binding region, while teprotumumab does.² 

A new Phase III trial into the drug, Thrive (ClinicalTrials.gov Identifier: NCT05176639), “will assess efficacy and safety of VRDN-001, a full antagonist antibody to IGF-1R, in both a standard 8-infusion regimen and a shortened 5-infusion regimen to define treatment regimens that balance efficacy, safety, and patient treatment burden.”³