Viridian Therapeutics, Inc. released positive long-term (52-week) clinical findings from its phase 3 THRIVE clinical trial evaluating veligrotug (veli), its lead product candidate, for the treatment of thyroid eye disease (TED).
First, let’s talk about this asset.
Veli (originally referred to as VRDN-001) is an investigational differentiated candidate included in Viridian’s portfolio of anti-insulin-like factor-1 receptor (IGF-1R) monoclonal antibodies.
- What they do: Block cell surface receptor activity and target antibody and protein engineering for specific diseases and autoimmune disorders (including TED).
Why focus on IGF-1R?
This is overexpressed in TED; thus, blocking IGF-1R signaling results in reduced disease activity, proptosis, and diplopia in the disease.
Also to keep in mind: An IGF-IR is known as a "clinically and commercially validated target” for TED, with additional involvement in:
- Development
- Metabolism
- Immune regulation
So what’s the potential for veli?
As with the company’s other IGF-IR monoclonal antibody under clinical investigation (dubbed VRDN-003), veli could potentially reduce tissue swelling and inflammation associated with TED.
- Its delivery method: Intravenous (IV) injection.
- And dosing schedule: Five, 30-minute infusions (3 weeks apart)
Didn’t the FDA just grant it a major designation?
It did! In fact, earlier this month veli received FDA Breakthrough Therapy designation for its TED indication, supporting its expedited clinical development.
What it was based on: Veli’s clinical performance, based on its:
- Consistent and robust improvement and resolution of diplopia in chronic TED
- Rapid onset of proptosis response
Why this is important: Such a designation gives Viridian a major advantage for the therapeutic’s clinical pathway to regulatory approval, as it now has the potential to be eligible for Priority Review.
Let’s stick with this clinical data … how has veli performed so far?
Veli was previously evaluated in a proof-of-concept phase 1/2 study for its potential to deliver rapid improvements in symptoms among chronic TED patients (including proptosis).
That data: As we reported in 2023, the asset was generally well-tolerated and also demonstrated a favorable safety and tolerability profile similar to prior 6-week data. See the full rundown.
And its current evaluations?
Two global phase 3 trials are ongoing:
- THRIVE (NCT05176639)
- Positive topline (15-week) data reported in September 2024
- THRIVE 2 (NCT06021054)
- Positive data reported in December 2024.
To note: Veli was generally well-tolerated and met all of its primary and secondary endpoints in both trials.
Now for a refresh of the THRIVE trial’s setup.
Its purpose: To determine the safety and efficacy of veli in patients with active TED.
- The participants: 113 patients (ages 18+) enrolled at 52 sites. See here for participant criteria.
- The setup: Patients randomized to receive either five infusions every 3 weeks of:
- Veli 10 mg/kg (n = 75)
- Placebo (n = 38)
- The outcome measures:
- Primary:
- Participants with treatment-emergent AEs (TEAEs; up to 52 weeks)
- Proptosis responder rate, based on patients with a ≥ 2 mm reduction from baseline (at Week 15)
- See here for secondary outcome measures
- Primary:
Now, what did the 52-week data show?
The focus: Proptosis responder rate.
Specifically: Nearly three-fourths (70%) of veli-treated patients who were proptosis responders at Week 15—and continued follow-up to the end of the study—maintained their proptosis response.
- To note: The 15-week data found 70% of veli-treated patients were proptosis responders.
And what exactly did this entail?
These patients were part of the 70% of responders at Week 15 who still had a 2-mm reduction in proptosis when compared to baseline at Week 52.
- Notably: This was achieved without worsening in the fellow eye (≥2 mm increase).
To compare: See here for the 15-week data (in which just 5% of placebo-treated patients were proptosis responders, with a mean reduction of 0.5 mm [2.4 mm placebo-adjusted; p < 0.0001]).
Got it. Were there any changes in veli’s safety profile?
In the follow-up period—no.
As for adverse events (AEs): The majority reported at the Week 15 point were resolved by Week 52.
- These AEs were mild and resulted in a low rate of discontinuation (4%) among veli-treated patients.
Sounds promising … so let’s get down to the basics: What makes it unique?
As Viridian President and CEO Steve Mahoney noted, veli is the “only therapy that has demonstrated statistically significant and clinically meaningful improvement and resolution of diplopia in both active and chronic TED.”
- And as for its efficacy: "Veli also showed a rapid onset of treatment effect, including an improvement in proptosis response in as few as 3 weeks after just one infusion,” he added.
In other words: Veli could become a potentially groundbreaking treatment option for TED patients.
Nice! So what’s next?
Mahoney stated the company plans to submit a Biologics License Application (BLA) for veli’s TED indication by the second half (H2) of 2025.
The potential plan: A commercial launch to the U.S. market in 2026.