- On track to initiate two phase 3 clinical trials of VRDN-003 in August 2024 -
- REVEAL-1 and REVEAL-2, will evaluate two active dosing regimens of subcutaneously (SC) administered VRDN-003 in active and chronic thyroid eye disease (TED), with topline readout anticipated in the first half of 2026 for both trials -
- VRDN-003 Biologics License Application (BLA) submission anticipated by year-end 2026 -
- VRDN-003 is the only half-life extended anti-IGF-1R antibody in clinical development with the potential for convenient SC dosing as infrequently as every 8 weeks, for a total of 3 administrations -
Viridian Therapeutics, Inc. reported details of its plans to initiate a phase 3 clinical trial program for its SC VRDN-003 product candidate for patients with moderate-to-severe TED.
“We are very pleased to have completed a positive Type C meeting with the FDA and to take this next step towards rapidly bringing a highly differentiated treatment option to patients living with TED,” said Steve Mahoney, Viridian’s president and CEO. “We view VRDN-003 as a potentially best-in-class anti-IGF-1R product candidate that is designed to preserve the compelling IGF-1R clinical response we have seen in our earlier proof-of-concept studies of VRDN-001. We believe this product profile could maximize convenience as a low-volume, infrequent subcutaneous injection and provide better access to treatment for patients.”
Phase 3 clinical trials in active and chronic TED
Viridian is planning to initiate two randomized, double-masked, placebo-controlled phase 3 clinical trials designed to evaluate the efficacy and safety of subcutaneously administered VRDN-003 in patients with active and chronic TED, named REVEAL-1 and REVEAL-2, respectively. These clinical trials are expected to initiate in August 2024.
In REVEAL-1, approximately 84 patients will be randomized in a 1:1:1 ratio to receive VRDN-003 SC or placebo every 4 weeks or every 8 weeks. Patients will receive an initial 600mg loading dose given as two 300mg injections, followed by single injections of 300mg thereafter for a total of 6 administrations in the 4-week dosing regimen and a total of 3 administrations in the 8-week regimen.
In REVEAL-2, approximately 126 patients will be randomized in the same manner for the same dosing regimens. The primary endpoint in each clinical trial will be proptosis responder rate, based on the achievement of at least 2mm improvement in proptosis from baseline at week 24, versus placebo. Subsequently, patients will be followed for an additional 28 weeks. Additional outcome measures in each trial will include changes from baseline in proptosis, clinical activity score (CAS) and diplopia.
“The current standard of care in TED requires 8 intravenous doses, representing a significant burden for patients,” said Tom Ciulla, Viridian’s CMO. “Subcutaneous VRDN-003 could transform the treatment experience for patients with TED.”
Viridian anticipates topline data for both clinical trials to be available in the first half of 2026 and to file a BLA by the end of 2026. The company plans to launch VRDN-003 with a commercially available autoinjector pen.
About VRDN-003
VRDN-003 is a potential best-in-class, subcutaneously administered anti-IGF-1R antibody in development for TED. VRDN-003 has the same binding domain as VRDN-001, was engineered to have a longer half-life, and acts as a full antagonist of IGF-1R. IGF-1R inhibition is the only approved mechanism of action that has been clinically and commercially validated for TED and has shown to be highly effective in treating the disease.
Phase 1 results in healthy volunteers showed a VRDN-003 half-life of 40-50 days which is 4-5x the half-life of VRDN-001. Further, pharmacokinetic modeling predicts that convenient dosing regimens of VRDN-003 (e.g., a low volume subcutaneous injection once every 4 or 8 weeks) could achieve exposure levels of VRDN-003 that are equivalent to those of VRDN-001 that produced clinically meaningful results in TED patients in a phase 2, proof-of-concept clinical trial.