veligrotug (VRDN-001) / Sanofi, Viridian Therap, Zenas BioPharma, AbbVie, ZAI Lab - LARVOL DELTA

VRDN-001-302: An Open-label Study for Non-responders of VRDN-001-101 and VRDN-001-301 (OLE) (clinicaltrials.gov) - P3 | N=143 | Active, not recruiting | Sponsor: Viridian Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Jul 2025

Enrollment closed • Trial completion date • Ophthalmology • Thyroid Eye Disease

STRIVE: A Randomized, Controlled, Safety and Tolerability Study of VRDN-001 in Participants with Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=231 | Active, not recruiting | Sponsor: Viridian Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Ophthalmology • Thyroid Eye Disease

Veligrotug (VRDN-001), a Full Antagonist Monoclonal Antibody to IGF-1 Receptor, in Active Thyroid Eye Disease (TED): THRIVE Phase 3 Efficacy and Safety Topline Results (ARVO 2025) - P3 | "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • P3 data • P3 data: top line • Ocular Inflammation • Ophthalmology • IGF1

Viridian Therapeutics Highlights Recent Progress and Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "TED Portfolio Progress: Veligrotug:...BLA submission is on track for the second half of 2025, with an MAA submission to the European Medicines Agency expected in the first half of 2026."

EMA filing • FDA filing • Thyroid Eye Disease

Reduced Proptosis and Muscle/Fat Volume by MRI/CT in a Proof-of-Concept Study in TED Shows Potential for Disease-Modifying Effects of VRDN-001, a Targeted TED Therapy (ATA 2024) - "In this small number of patients with active TED, MRI/CT analysis shows potential for a disease-modifying effect of VRDN-001, with reductions of EOM and OF associated with improvements in proptosis at 6 weeks that continued through 12 weeks (9 weeks beyond last treatment)."

Immunology • Ophthalmology • Thyroid Eye Disease • IGF1

Subcutaneous Administration of VRDN-003, a Next-Generation Full Antagonist Antibody to IGF-1R, in Patients With Thyroid Eye Disease (TED): Two Randomized Placebo-Controlled Clinical Studies (REVEAL-1 and REVEAL-2) (ATA 2024) - "Objective: VRDN-001 and VRDN-003 are full antagonist antibodies to the IGF-1 receptor (IGF-1R). VRDN-003 is in development as a sub-cutaneous treatment for TED with the goal of reducing the treatment burden currently associated with IV infusions. The REVEAL-1 and REVEAL-2 randomized, double-masked, placebo-controlled trials will be the first to assess subcutaneous VRDN-003 in patients with TED."

Clinical • Ophthalmology • Thyroid Eye Disease • IGF1

THRIVE Phase 3 Trial of VRDN-001 in Active Thyroid Eye Disease (TED): Next Generation Insulin-like Growth Factor-1 Receptor Blockade (ATA 2024) - "Topline results from THRIVE, a double-masked, placebo-controlled phase 3 registrational trial, will provide an initial view on the clinical safety and efficacy outcomes of a full treatment course (5 IV infusions) of VRDN-001 in active TED."

Late-breaking abstract • P3 data • Ophthalmology • Thyroid Eye Disease

Subcutaneous VRDN-003 vs. VRDN-001, Full Antagonist Antibodies to IGF-1R for TED: Phase 1 Safety/PK/PD Studies (AAO 2024) - "Conclusion At two dose levels, a single dose of VRDN-003 was well tolerated, had four to five times longer half-life than VRDN-001 and demonstrated sustained increases in IGF-1 levels. Safety and efficacy of VRDN-003 SC will be assessed in clinical studies enrolling patients with TED."

Clinical • P1 data • PK/PD data • Ocular Inflammation • Ophthalmology • IGF1

An Efficacy, Safety, and Tolerability Study of Veligrotug (VRDN-001), in Participants with Chronic Thyroid Eye Disease (TED) (THRIVE-2) (clinicaltrials.gov) - P3 | N=188 | Active, not recruiting | Sponsor: Viridian Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Ophthalmology • Thyroid Eye Disease

VRDN-001, a Targeted TED Therapy: Disease-Modifying Effects on Proptosis and Muscle/Fat Volume by MRI/CT in a Proof-of-Concept Study in TED (AAO 2024) - "Mean changes from baseline at 6 weeks for VRDN-001 versus placebo were −4.6 mm versus −0.2 mm for proptosis, −31% versus −10% for EOM and −19% versus −2% for OF; changes at 12 weeks were −5.9 mm versus −0.1 mm for proptosis, −37% versus −17% for EOM and −37% versus 0% for OF. Conclusion In this small number of patients with TED, MRI/CT analysis shows potential for a disease-modifying effect of VRDN-001, with reductions of EOM and OF associated with improvements in proptosis at 6 weeks that continued through 12 weeks (9 weeks beyond last treatment)."

Ophthalmology

Viridian Therapeutics to Webcast VRDN-001 Phase 3 THRIVE Topline Results on September 10, 2024 (Businesswire) - "Viridian Therapeutics...will host a conference call and webcast to report topline data for the THRIVE phase 3 clinical trial, evaluating VRDN-001 in patients with active TED, on Tuesday, September 10, 2024 at 8:00am ET."

P3 data: top line • Thyroid Eye Disease

Viridian Therapeutics Announces Completion of THRIVE-2 Enrollment for VRDN-001 in Patients with Chronic Thyroid Eye Disease (TED) (Businesswire) - "Viridian Therapeutics...announced that enrollment is complete in THRIVE-2, its phase 3 clinical trial for VRDN-001 in patients with chronic TED. THRIVE-2 enrolled 188 patients globally and exceeded the enrollment target of 159 patients due to patient demand. Approximately 40% of the enrolled patients were from US sites. Topline data from THRIVE-2 is on track for readout by year-end 2024....Topline data for THRIVE is on track for readout in September 2024."

Enrollment status • P2 data • P3 data: top line • Thyroid Eye Disease

VRDN-003, a Full Antagonist Antibody to IGF-1R for Thyroid Eye Disease (TED): Phase 1 Results Show Potential for Subcutaneous Administration (ETA 2024) - "These results show the potential for VRDN-003 SC dosing regimens. A single dose of VRDN-003 was well tolerated with an extended half-life 4–5 times longer than that of its parent molecule, VRDN-001. Safety and efficacy of VRDN-003 SC are planned to be further assessed in clinical studies enrolling patients with TED."

P1 data • CNS Disorders • Insomnia • Ophthalmology • Sleep Disorder • Thyroid Eye Disease

Emerging therapies in the medical management of thyroid eye disease. (PubMed, Front Ophthalmol (Lausanne)) - "Teprotumumab - an anti-IGF-1R monoclonal antibody that has recently emerged as a first-line therapy for active, moderate-to-severe TED - has demonstrated statistically significant improvements in proptosis, diplopia, clinical activity score, and quality of life compared to placebo. Currently under investigation are several other agents, with varying administration modalities, that aim to inhibit IGF-1R: VRDN-001 (intravenous), VRDN-002 or VRDN-003 (subcutaneous), lonigutamab (subcutaneous), and linsitinib (oral). Tocilizumab, a monoclonal antibody of interleukin 6, has played a role in the management of multiple autoimmune and inflammatory conditions and may offer promise in TED...Among the agents under investigation that aim to decrease ocular morbidity associated with TED are agents that IGF-1R, interleukin 6, and the neonatal Fc receptor. The management of TED continues to expand with novel immunologic approaches for disease therapy."

Journal • Review • Endocrine Disorders • Grave’s Disease • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • IL6

A Randomized, Active Controlled, Safety and Tolerability Study of VRDN-001 in Participants With Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=212 | Recruiting | Sponsor: Viridian Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Ophthalmology • Thyroid Eye Disease

Inhibition of IGF-1 Receptor Signaling and Ocular Fibroblast Cell Growth by VRDN-001 vs Teprotumumab (ENDO 2024) - "Prior in vitro research showed that compared with teprotumumab, VRDN-001 provided more complete inhibition of IGF-1R autophosphorylation and AKT phosphorylation (PI3K signaling pathway). The current research extends these findings by showing that VRDN-001 also provides more complete inhibition of IGF-1-mediated ERK phosphorylation (MAPK signaling pathway activation) and fibroblast cell growth. While teprotumumab and VRDN-001 share a similar mechanism of action, their binding properties are distinct, which may explain the differences in ligand blocking, antagonism of signaling, and inhibition of functional activity."

Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • IGF1

Clinical Activity and Safety of VRDN-001, a Full Antagonist Antibody to Insulin-like Growth Factor-1 Receptor, in Active and Chronic Thyroid Eye Disease (ENDO 2024) - P3 | "At baseline, mean duration of TED and mean proptosis were 7.4 months and 24 mm in the active TED cohort vs 7.8 years and 22 mm in the chronic TED cohort. After 2 infusions at 6 weeks, all doses of VRDN-001 showed clinically meaningful improvements in outcome measures in both TED populations. The exophthalmometry proptosis responder rate (% of patients with ≥2-mm reduction) was 71% (15/21, active) and 42% (5/12, chronic), with a mean proptosis reduction from baseline of 2.3 mm (active) and 1.6 mm (chronic)."

Clinical • Ophthalmology • Pain • Thyroid Eye Disease

Clinical Activity and Safety of VRDN-001, a Full Antagonist Antibody to Insulin-like Growth Factor-1 Receptor, in Active and Chronic Thyroid Eye Disease (ENDO 2024) - P3 | "At baseline, mean duration of TED and mean proptosis were 7.4 months and 24 mm in the active TED cohort vs 7.8 years and 22 mm in the chronic TED cohort. After 2 infusions at 6 weeks, all doses of VRDN-001 showed clinically meaningful improvements in outcome measures in both TED populations. The exophthalmometry proptosis responder rate (% of patients with ≥2-mm reduction) was 71% (15/21, active) and 42% (5/12, chronic), with a mean proptosis reduction from baseline of 2.3 mm (active) and 1.6 mm (chronic)."

Clinical • Ophthalmology • Pain • Thyroid Eye Disease

VRDN-003, a Full Antagonist Antibody to the IGF-1 Receptor for Thyroid Eye Disease (TED): Safety and Pharmacokinetic Results of Subcutaneous Administration in Healthy Volunteers (ENDO 2024) - "A single dose of VRDN-003 administered IV or SC to HVs was well tolerated and showed favorable PK for SC administration including a half-life of 40-50 days, 4-5 times longer than its parent molecule, VRDN-001. These results show the potential for VRDN-003 SC dosing regimens with the goal of reducing the treatment burden associated with achieving IGF-1R blockade in TED. Safety and efficacy of VRDN-003 SC will be further assessed in planned clinical studies enrolling patients with TED.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation."

Clinical • PK/PD data • CNS Disorders • Insomnia • Ophthalmology • Sleep Disorder • Thyroid Eye Disease • IGF1

A Safety, Tolerability and Efficacy Study of VRDN 001 in Healthy Volunteers and Persons With Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=154 | Active, not recruiting | Sponsor: Viridian Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Ophthalmology • Thyroid Eye Disease

A Randomized, Active Controlled, Safety and Tolerability Study of VRDN-001 in Participants With Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=212 | Not yet recruiting | Sponsor: Viridian Therapeutics, Inc.

New P3 trial • Ophthalmology • Thyroid Eye Disease

VRDN-001 vs teprotumumab inhibition of IGF-1 receptor signaling and ocular fibroblast cell growth (ARVO 2024) - "VRDN-001 inhibited IGF-1–mediated MAPK pathway activation and cell growth, adding to the previous reports of IGF-1R autophosphorylation and PI3K signaling inhibition. These data suggest that VRDN-001 is a more robust IGF-1R inhibitor than teprotumumab through these distinct pathways in vitro. While teprotumumab and VRDN-001 share a similar mechanism of action, their binding properties are distinct, which may explain the differences in ligand blocking, signaling antagonism, and inhibition of functional activity."

Ocular Inflammation • Ophthalmology • IGF1

An Open-label Study for Participants Who Are Non-responders at the End of Treatment Assessment on the VRDN-001-101 and VRDN-001-301 Pivotal Studies (clinicaltrials.gov) - P3 | N=143 | Recruiting | Sponsor: Viridian Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2023 ➔ Feb 2023

Enrollment open • Trial initiation date • Ophthalmology • Thyroid Eye Disease

Frontline Insights in Multiple Myeloma Treatment : Episode 7: Real-world Multiple Myeloma Treatment: Insights and Challenges (AJMC) - "This is a video synopsis/summary of a Peer Exchange featuring...Amrita Krishnan, MD...discusses real-world studies(RWS) comparing DRd (daratumumab) to other regimens. One study compared DRd from the MAIA trial with Flatiron Health database data, demonstrating a lower risk of progression for patients receiving DRd. Another retrospective study compared patients receiving DRd patients with those receiving VRd (bortezomib, lenalidomide, dexamethasone), reinforcing the potential usefulness of anti-CD38 in the upfront setting. Krishnan highlights challenges in collecting dosing data in RWS, emphasizing the need to refer to original trials for guidance. The conversation underscores the value of real-world data in corroborating and adjusting treatment strategies based on the actual patient population."

Media quote

Study of ZB001 in Chinese Patients With Thyroid Eye Disease (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Zenas BioPharma (USA), LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Ophthalmology • Thyroid Eye Disease