Viridian Unveils Phase 3 VRDN-003 Program for Thyroid Eye Disease

Viridian Therapeutics, Inc., a biotechnology firm committed to creating advanced treatments for severe and rare ailments, has announced plans to commence phase 3 clinical trials for their subcutaneous VRDN-003 candidate aimed at patients with moderate-to-severe thyroid eye disease (TED). The CEO of Viridian, Steve Mahoney, expressed enthusiasm about the progress, noting that a positive Type C meeting with the FDA has paved the way for the trials. He emphasized VRDN-003’s potential to be a superior anti-IGF-1R product, designed for convenient, infrequent subcutaneous injections, improving accessibility for patients.

The phase 3 clinical trials, named REVEAL-1 and REVEAL-2, will be randomized, double-masked, and placebo-controlled, assessing both efficacy and safety of VRDN-003 in active and chronic TED patients. These trials are set to begin in August 2024. In REVEAL-1, 84 patients will be randomized to receive either the VRDN-003 or a placebo every 4 or 8 weeks. The initial dose will consist of two 300mg injections totaling 600mg, followed by 300mg injections thereafter. This will result in six administrations for the 4-week regimen and three for the 8-week regimen. Similarly, REVEAL-2 will include 126 patients randomized to the same dosages and intervals. The main endpoint for both trials is the proptosis responder rate, defined by a minimum of 2mm improvement in proptosis from the baseline at week 24, compared to the placebo group. Patients will then be monitored for an additional 28 weeks. Other outcome measures will include changes in proptosis, clinical activity score (CAS), and diplopia.

Tom Ciulla, Viridian's Chief Medical Officer, highlighted that the current standard of care for TED involves eight intravenous doses, which is cumbersome for patients. He believes that the subcutaneous administration of VRDN-003 could significantly enhance the treatment experience for TED patients.

Viridian expects to release topline data from both clinical trials in the first half of 2026 and aims to submit a Biologics License Application (BLA) for VRDN-003 by the end of that year. The company also plans to introduce VRDN-003 with a commercially available autoinjector pen.

VRDN-003 stands out as a potential best-in-class treatment for TED, featuring subcutaneous administration and a longer half-life compared to its predecessor, VRDN-001. With the same binding domain as VRDN-001, VRDN-003 acts as a full antagonist of IGF-1R, which is a validated mechanism of action for treating TED. Initial phase 1 trials in healthy volunteers revealed that VRDN-003 has a half-life of 40-50 days, significantly longer than VRDN-001. Pharmacokinetic models suggest that the low-volume subcutaneous injection administered every 4 or 8 weeks can achieve exposure levels similar to those of VRDN-001, which demonstrated effective results in a phase 2 proof-of-concept trial for TED patients.

Viridian Therapeutics, headquartered in Waltham, Massachusetts, is dedicated to engineering and developing advanced medicines for serious and rare diseases. Besides VRDN-003, the company is also working on other candidates like VRDN-001, VRDN-006, and VRDN-008, targeting diseases including TED and autoimmune disorders.