Viridian Therapeutics, Inc. announced the release of positive preliminary data from the ongoing phase 1/2 clinical trial evaluating VRDN-001 in patients with chronic thyroid eye disease (TED).
Refresh me on VRDN-001.
VRDN-001 is an anti-insulin-like growth factor 1 receptor (IGF-1R) antibody that blocks cell surface receptor activity, leading to a potential reduction in tissue swelling and inflammation associated with TED.
And this trial?
The placebo-controlled, proof-of-concept study consists of multiple randomized, placebo-controlled cohorts assessing the potential for VRDN-001 to deliver rapid improvement of TED symptoms—including proptosis.
VRDN-001 was evaluated among two cohorts—one cohort received a 3 mg/kg dose and the second received a 10 mg/kg dose—which were each comprised of six patients randomized to drug and two participants randomized to placebo.
Two infusions of VRDN-001 were intravenously administered and evaluated 3 weeks apart, with efficacy measured 6 weeks following the first dose.
How about patient eligibility?
Patients were required to be diagnosed with chronic TED and have documented ocular symptoms / signs at least 1 year prior to screening as well as proptosis of ≥3 mm above normal values for gender and race.
There was no inclusion criteria regarding the clinical activity score (CAS) (mean CAS = 3.3), allowing for randomization.
What was measured?
Patients were assessed for changes in the following (at week 6):
- Proptosis
- As measured from baseline by exophthalmometry and magnetic resonance imaging (MRI).
- CAS
- Diplopia
And the findings?
In all, VRDN-001’s safety and tolerability profile was consistent with previously-reported data from patients with active TED (see here for 6-week data from the phase 1/2 trial in January 2023).
VRDN-001 was found to be generally well-tolerated among patients in both dose cohorts.
There were no reported serious adverse events (SAEs), hearing impairment, or drug-related hyperglycemia as of the most recent cut-off date (May 30, 2023) for follow-up observation.
Talk numbers.
Between both cohorts, VRDN-001-treated patients exhibited a lower mean proptosis at baseline versus placebo (22.2 mm vs 25.00 mm, respectively)
The mean CAS showed a 50% to 72% reduction at week 6:
- 3.3. (mean baseline CAS)
- -1.9 (mean CAS reduction from baseline of all patients)
- -2.3 (mean CAS reduction from baseline of patients CAS > 0 at baseline)
Of note, two patients from the 10 mg/kg cohort (with a baseline CAS of 0) were excluded.
What about diplopia?
A reported 5 out of 12 patients (41.6%) from both cohorts exhibited diplopia at baseline; however, at week 6, none of the VRDN-001-treated patients achieved a complete resolution.
So what’s next?
Viridian is also planning the THRIVE phase 3 trial design (based on FDA discussions), which will include a five-dose regimen of VRDN-001 and placebo arms only.
Per the company, topline data is expected by mid-2024.
Viridian also expects to launch the THRIVE-2 phase 3 trial of VRDN-001 in patients with chronic TED by Q3 2023; topline data is expected by the end of 2024.
That’s a lot… anything else planned on the horizon?
The company will use the 3 mg/kg dose cohorts fo VRDN-001 with either active or chronic TED to support a low-volume, subcutaneous (SC) product profile—concentrations of 150 mg/mL for a 300 mg/2 mL dose administration— for its three candidates:
- VRDN-001 SC
- Investigational new drug (IND) amendment filed in June 2023 (along with IND application for VRDN-003)
- Phase 1 trial initiation expected in Q3 2023, pending FDA clearance.
- VRDN-002 SC
- Phase 1 healthy volunteer trial completed for single IV and single-dose cohorts
- VRDN-003 SC
Pending FDA clearance, Viridian plans to choose one lead SC program by the end of 2023 and advance to a pivotal phase 2/3 trial by mid-2024.