Viridian Therapeutics, Inc. announced plans to initiate a phase 3 clinical trial program for moderate-to-severe thyroid eye disease (TED) featuring VRDN-003, its latest investigational candidate.
First, this company.
The Waltham, Massachusetts biopharmaceutical company is targeting antibody and protein engineering to develop differentiated candidates for various diseases, including TED and anti-neonatal Fc receptor (FcRn)-targeting candidates for autoimmune disorders.
In regards to TED, its portfolio includes:
- VRDN-001 (administered via intravenous [IV] infusion)
- Dosing: Five infusions, given 3 weeks apart with 30 minute infusion time
- See here for phase 1/2 trial data
- Currently undergoing two global phase 3 trials:
- THRIVE (NCT05176639)
- THRIVE-2 (NCT06021054)
- Dosing: Five infusions, given 3 weeks apart with 30 minute infusion time
- VRDN-003 (self-administered via subcutaneous [SC] injection)
Tell me more about these candidates.
Both assets are anti-insulin-like factor-1 receptor (IGF-IR) monoclonal antibodies that block cell surface receptor activity, leading to a potential reduction in tissue swelling and inflammation associated with TED.
- Note: These transmembrane receptors are also involved in development metabolism and immune regulation as a “clinically and validated target” for TED treatment
And the clinical data on VRDN-001 so far?
Based on that phase 1/2 data, the candidate was found to be generally well-tolerated among two cohorts, with no serious adverse events observed among all chronic TED participant users.
The numbers:
- VRDN-001-treated patients exhibited a lower mean proptosis at baseline versus placebo (22.2 mm vs 25.00 mm, respectively)
- A mean clinical activity score (CAS) demonstrated a 50% to 72% reduction by week 6
- A total of 41.6% of patients exhibited diplopia at baseline; however, none of the VRDN-001-treated patients achieved a complete resolution
See here and here for our full coverage.
Now let’s zero in on VRDN-003.
While similar to VRDN-001 and with the same binding domain as its parent molecule, VRDN-003 SC is engineered with a longer half-life.
Its dosing regimen: Every 8 or 4 weeks.
Plus: Per Viridian, it’s intended to maintain VRDN-001’s clinical response while also significantly increasing both patient convenience and (potentially) safety.
Moving on to this phase 3 program …
The randomized, double-masked, placebo-controlled phase 3 REVEAL-1 and REVEAL-2 studies will analyze the safety and efficacy of VRDN-003 SC for active and chronic TED.
- Study details for both:
- Estimated participants: 85 (REVEAL-1); 126 (REVEAL-2)
- Randomization: 1:1:1 ratio
- Dosings: VRDN-003 SC or placebo every 4 or 8 weeks
- Initial loading dose: 600 mg (via two 300 mg injections)
- Following doses: 300 mg single injections
- Total doses: six (for 4-week regimen); three (for 8-week regimen)
- Estimated participants: 85 (REVEAL-1); 126 (REVEAL-2)
What’s being measured?
The primary endpoint for both trials will be the proptosis responder rate, as measured by achieving at least a 2 mm improvement in proptosis from baseline at week 24 (vs placebo), according to Viridian.
- Following this: Participants will be followed for an extra 28 weeks.
Similar to the VRDN-001 studies, other outcome measures will include changes in:
- CAS
- Proptosis
- Diplopia
So … when are these trials expected to kick off?
The company is anticipating August 2024 for initiation of REVEAL-1 and REVEAL-2.
And when can we expect data?
Topline data is expected for both studies by H1 2026 (so we’ve got some time).
Then what?
Pending positive clinical data from these trials, Viridian intends to file a Biologics License Application (BLA) by the end of 2026.
A tentative launch of VRDN-003 with a commercially-available autoinjector pen is also in the works, according to the company.