Viridian Therapeutics, Inc. released positive topline results from its phase 3 THRIVE clinical trial evaluating VRDN-001 (now dubbed “veligrotug”), its investigational candidate, for the treatment of chronic thyroid eye disease (TED).
First, background on this candidate.
The biopharmaceutical company is developing differentiated candidates for specific diseases (such as TED) and autoimmune disorders by targeting antibody and protein engineering.
For TED: Viridian’s portfolio consists of two investigational assets:
- Veligrotug (lead candidate)
- VRDN-003
Now explain what veligrotug is.
As with VRDN-003, veligrotug is an anti-insulin-like factor-1 receptor (IGF-IR) monoclonal antibody that blocks cell surface receptor activity.
- The intended result: A potential reduction in tissue swelling and inflammation associated with TED.
To note: These IGF-IR transmembrane receptors also play key roles in development, metabolism, and immune regulation—and are reported to be instrumental in TED’s pathogenesis.
And the treatment regimen?
Veligrotug is formulated to be administered via an intravenous (IV) infusion (compared to VRDN-003’s subcutaneous injection).
The dosing: Five 30-minute infusions administered 3 weeks apart.
- Comparatively: VRDN-003 is administered every 4 to 8 weeks.
And what has clinical data demonstrated so far?
The company released phase 1/2 data from a placebo-controlled, proof-of-concept study in January 2023 and July 2023, in which VRDN-001 was found to be generally well-tolerated and resulted in no serious adverse events (AEs) among all chronic TED participant users.
Specifically:
- 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
Now this phase 3 study.
The global phase 3 THRIVE study (NCT05176639) is evaluating the safety and efficacy of veligrotug in patients with active TED.
- Participant info: 113 patients (ages 18+) enrolled at 52 sites.See here for participant criteria.
- The setup: Patients randomized to receive either five infusions of:
- Veligrotug 10 mg/kg (n = 75)
- Placebo (n = 38)
- The outcome measures:
- Primary:
- Participants with treatment-emergent AEs (TEAEs) (time frame: up to 52 weeks)
- Proptosis responder rate, based on patients with a ≥ 2 mm reduction from baseline (time frame: Week 15)
- See here for secondary outcomes
- Primary:
And the findings?
Right off the bat: At 15 weeks, Viridian reported that the study met all its primary and secondary endpoints following five IV infusions of veligrotug.
- Highly statistically significant improvements (p < 0.0001) were noted on all measured TED signs and symptoms
Give me some numbers.
Let’s hone in on three key areas:
- Proptosis (measured by exophthalmometry
- Proptosis responder rate (PRR)
- 70% of veligrotug patients
- 5% of placebo patients (64% place-adjusted) (p < 0.0001)
- Mean reduction
- 2.99 mm from baseline for veligrotug patients
- 0.5 mm (2.4 mm placebo-adjusted) (p < 0.0001)
- Proptosis responder rate (PRR)
- Diplopia
- Complete resolution
- 54% of veligrotug patients
- 12% of placebo patients (43% placebo-adjusted) (p < 0.0001)
- Response
- 63% of veligrotug patients
- 20% of placebo patients (43% placebo-adjusted) (p < 0.0001)
- Complete resolution
- CAS
- Reduction to 0 or 1
- 64% of veligrotug patients achieved maximal or near-maximal therapeutic effect
- 18% of placebo patients (46% placebo-adjusted) (p < 0.0001)
- Mean reduction
- 3.4-point reduction from baseline for veligrotug patients
- 1.7-point reduction for placebo patients (1.7-point placebo-adjusted) (p < 0.0001)
- Reduction to 0 or 1
Let’s talk safety data.
Virdian noted that the candidate was generally well tolerated, with “a safety profile consistent” with its previous clinical evaluations.
As for AEs: The majority observed were mild, with a low rate of discontinuation among veligrotug patients (just 4%).
- Of interest: Hearing impairment AEs (with a 5.5% placebo-adjusted rate) were observed in:
- 16% of veligrotug patients
- 10.5% of placebo patients
And the overall responder rate among participants?
This was defined as patients who achieved a proptosis response and a ≥2-point reduction in CAS from baseline without worsening in the fellow eye in either proptosis (2mm increase) or CAS (2-point increase).
The data:
- 67% of veligrotug patients achieved an overall response
- 5% of placebo patients (61% placebo-adjusted)
What did the company have to say about this?
Viridian President and CEO Steve Mahoney noted the company’s excitement at veligrotug achieving both efficacy and safety—and surpassing their safety profile expectations.
He emphasized the candidate’s unique, abbreviated dosing regimen “that has the potential to bring a more convenient treatment option with lower IV burden for patients, compared to the current standard of care.”
Both veligrotug and VRDN-003—which the company recently kicked off two phase 3 trials for—have the potential to become the preferred treatments for TED patients, he stated.
So what’s next?
With the THRIVE-2 study (NCT06021054), a second phase 3 trial evaluating veligrotug among chronic TED patients, currently underway, Viridian expects to release a topline data readout by the end of Q4 2024.
And then?
The company plans on submitting a Biologics License Application (BLA) to the FDA for veligrotug’s chronic TED indication by H2 2025.