8-K: Viridian Therapeutics Announces Positive Topline Results for Veligrotug in Thyroid Eye Disease

Viridian Therapeutics' veligrotug (VRDN-001) met all primary and secondary endpoints in a Phase 3 trial for active thyroid eye disease, showing significant improvements in key disease indicators.

Summary

• Viridian Therapeutics announced positive topline results from the THRIVE Phase 3 trial for veligrotug (VRDN-001) in patients with active thyroid eye disease (TED).
• The trial met its primary and all secondary endpoints at 15 weeks, demonstrating statistically significant improvements in signs and symptoms of TED.
• Veligrotug showed a rapid onset of action, with 53% of patients achieving a proptosis response after just one infusion.
• The study enrolled 113 patients, with 75 receiving veligrotug and 38 receiving a placebo.
• Patients on veligrotug experienced a 70% proptosis responder rate compared to 5% in the placebo group, a 64% placebo-adjusted difference.
• The mean reduction in proptosis was 2.9 mm for veligrotug versus 0.5 mm for placebo, a 2.4 mm placebo-adjusted difference.
• Complete resolution of diplopia was achieved in 54% of veligrotug patients compared to 12% of placebo patients, a 43% placebo-adjusted difference.
• A 63% diplopia response was observed in the veligrotug group versus 20% in the placebo group, a 43% placebo-adjusted difference.
• 64% of patients on veligrotug achieved a maximal or near-maximal therapeutic effect on the Clinical Activity Score (CAS), compared to 18% on placebo, a 46% placebo-adjusted difference.
• The mean reduction in CAS was 3.4 points for veligrotug versus 1.7 points for placebo, a 1.7 point placebo-adjusted difference.
• An overall response was achieved by 67% of patients on veligrotug compared to 5% on placebo, a 61% placebo-adjusted difference.
• Veligrotug was generally well-tolerated, with a low 4% discontinuation rate and no treatment-related serious adverse events.
• The placebo-adjusted rate of hearing impairment adverse events was 5.5% in the THRIVE trial.
• The company completed enrollment for the THRIVE-2 trial for chronic TED in July 2024, with topline data expected by year-end 2024.
• Viridian anticipates submitting a Biologics License Application (BLA) for veligrotug in the second half of 2025.
• Two Phase 3 trials for VRDN-003, REVEAL-1 and REVEAL-2, were initiated in August 2024, with topline data expected in the first half of 2026 and a BLA submission by year-end 2026.
• Viridian has $571.4 million in cash, cash equivalents, and short-term investments as of June 30, 2024, providing a cash runway into the second half of 2026.

Sentiment

Score: 9

Explanation: The document presents very positive results from a Phase 3 trial, with strong efficacy and a good safety profile, and a clear path to regulatory approval. The company also has a strong cash position.

Positives

• The THRIVE trial results were highly statistically significant across all endpoints.
• Veligrotug demonstrated a rapid onset of action, with a majority of patients showing improvement after just one infusion.
• The safety profile of veligrotug was favorable, with a low rate of discontinuations and no treatment-related serious adverse events.
• The company is on track to submit a BLA for veligrotug in the second half of 2025.
• The company has sufficient cash to fund operations into the second half of 2026.
• The initiation of Phase 3 trials for VRDN-003 is a positive step for the company's pipeline.

Negatives

• There was a 16% incidence of hearing impairment adverse events in patients receiving veligrotug, compared to 10.5% in the placebo group, resulting in a 5.5% placebo-adjusted rate.

Risks

• The company's forward-looking statements are subject to risks and uncertainties, including the potential for clinical trial results not to be representative of future trials.
• There are risks associated with regulatory approvals, manufacturing, and competition from other therapies.
• The company's financial position and cash runway are subject to change.
• There is a risk of delays in clinical drug development and regulatory processes.

Future Outlook

Viridian anticipates submitting a BLA for veligrotug in the second half of 2025 and for VRDN-003 by year-end 2026, with topline data from the VRDN-003 trials expected in the first half of 2026. The company believes both veligrotug and VRDN-003 have the potential to become preferred treatments for TED patients.

Management Comments

• Steve Mahoney, Viridian's President and CEO, stated that the THRIVE results met their high bars for both efficacy and safety and that they were particularly pleased to observe the rapid onset of clinically meaningful responses across all endpoints.
• Steve Mahoney also mentioned that the company believes veligrotug and VRDN-003 have the potential to become the preferred treatments for TED patients.
• Michael Yen, M.D., an investigator in THRIVE, stated that the data showed substantial improvements in proptosis, clinical activity score, and diplopia in patients with TED after just five infusions and that veligrotug showed a favorable safety profile.

Industry Context

This announcement is significant in the context of the thyroid eye disease treatment landscape, as it presents positive Phase 3 data for a new therapy, veligrotug, and highlights the potential of VRDN-003 as a subcutaneous treatment option. The results suggest a potential improvement over existing treatments, particularly with the rapid onset of action and favorable safety profile.

Comparison to Industry Standards

• The reported 70% proptosis responder rate for veligrotug is notably higher than the results seen with Tepezza, the current standard of care, which has shown proptosis response rates in the 40-50% range in its clinical trials.
• The 54% complete resolution of diplopia with veligrotug is also competitive, as Tepezza has shown diplopia resolution rates in the 40-50% range.
• The rapid onset of action, with 53% of patients achieving a proptosis response after just one infusion, is a potential advantage over other treatments that may take longer to show effects.
• The low rate of treatment-related serious adverse events and the 4% discontinuation rate for veligrotug are also favorable compared to some other therapies that may have higher rates of adverse events and discontinuations.
• The development of VRDN-003 as a subcutaneous injection is also a significant advancement, as it offers a more convenient administration method compared to the intravenous infusions required for Tepezza and veligrotug.

Stakeholder Impact

• Shareholders are likely to react positively to the strong clinical trial results and the company's progress towards regulatory approval.
• Patients with thyroid eye disease may benefit from the potential availability of new and effective treatment options.
• Employees of Viridian Therapeutics may be positively impacted by the company's success and growth.

Next Steps

• The company will continue the THRIVE-2 trial for chronic TED, with topline data expected by year-end 2024.
• Viridian plans to submit a BLA for veligrotug in the second half of 2025.
• The company will continue the REVEAL-1 and REVEAL-2 trials for VRDN-003, with topline data expected in the first half of 2026.
• Viridian plans to submit a BLA for VRDN-003 by year-end 2026.

Key Dates

Keywords

Thyroid Eye Disease, TED, Veligrotug, VRDN-001, VRDN-003, IGF-1R, Clinical Trial, Phase 3, Proptosis, Diplopia, Clinical Activity Score, BLA, Biologics License Application