Viridian Therapeutics Announces Positive Topline Results from Veligrotug Phase 3 THRIVE-2 Clinical Trial in Patients with Chronic Thyroid Eye Disease
Viridian Therapeutics announced positive topline results from the THRIVE-2 Phase 3 trial of veligrotug in chronic thyroid eye disease (TED). The trial met all primary and secondary endpoints with high statistical significance, achieving a 56% proptosis responder rate and diplopia responder rate at week 15. The drug was generally well-tolerated with 94% of patients completing treatment.
Key highlights include a 2.34mm mean reduction in proptosis, 32% complete diplopia resolution rate, and 54% of patients achieving maximal therapeutic effect on Clinical Activity Score. The company plans to submit a BLA in the second half of 2025. With $753 million cash position as of September 2024, Viridian has runway into second half of 2027.
Viridian Therapeutics ha annunciato risultati preliminari positivi dallo studio THRIVE-2 di Fase 3 su veligrotug per la malattia oculare tireoidiana cronica (TED). Lo studio ha raggiunto tutti gli endpoint primari e secondari con alta significatività statistica, ottenendo un tasso di risposta al proptosi del 56% e un tasso di risposta alla diplopia alla settimana 15. Il farmaco è stato generalmente ben tollerato, con il 94% dei pazienti che ha completato il trattamento.
I punti salienti includono una riduzione media di 2,34 mm nel proptosi, un tasso di risoluzione completa della diplopia del 32% e il 54% dei pazienti che ha raggiunto il massimo effetto terapeutico sul punteggio di attività clinica. L'azienda prevede di presentare una BLA nella seconda metà del 2025. Con una posizione di cassa di 753 milioni di dollari a settembre 2024, Viridian ha un margine di operatività fino alla seconda metà del 2027.
Viridian Therapeutics anunció resultados finales positivos del ensayo clínico THRIVE-2 de Fase 3 sobre veligrotug para la enfermedad ocular tiroidea crónica (TED). El ensayo cumplió con todos los objetivos primarios y secundarios con alta significancia estadística, logrando una tasa de respuesta en proptosis del 56% y una tasa de respuesta en diplopía en la semana 15. El medicamento fue generalmente bien tolerado, con el 94% de los pacientes completando el tratamiento.
Los aspectos más destacados incluyen una reducción media de 2,34 mm en proptosis, una tasa de resolución completa de diplopía del 32% y el 54% de los pacientes alcanzando el efecto terapéutico máximo en el Puntaje de Actividad Clínica. La compañía planea presentar una BLA en la segunda mitad de 2025. Con una posición de efectivo de 753 millones de dólares a partir de septiembre de 2024, Viridian tiene recursos suficientes hasta la segunda mitad de 2027.
비리디안 테라퓨틱스는 만성 갑상선 안병(TED)에 대한 벨리그로투그의 THRIVE-2 3상 시험에서 긍정적인 최종 결과를 발표했습니다. 이 시험은 높은 통계적 의미를 가지고 모든 주요 및 보조 목표를 달성하였으며, 15주차에 프로프토시스 반응률이 56%, 복시 반응률을 달성했습니다. 이 약물은 일반적으로 잘 견딜 수 있었고, 94%의 환자가 치료를 완료했습니다.
주요 하이라이트로는 프로프토시스의 평균 2.34mm 감소, 복시 완전 해소율 32%, 임상 활동 점수에서 최대 치료 효과에 도달한 환자가 54%인 점이 있습니다. 회사는 2025년 하반기에 BLA를 제출할 계획입니다. 2024년 9월 기준으로 7억 5300만 달러의 현금 보유량으로, 비리디안은 2027년 하반기까지 운영 자금을 보유하고 있습니다.
Viridian Therapeutics a annoncé des résultats préliminaires positifs de l'essai THRIVE-2 de Phase 3 sur veligrotug pour la maladie oculaire thyroïdienne chronique (TED). L'essai a atteint tous les objectifs principaux et secondaires avec une signification statistique élevée, obtenant un taux de réponse à la proptose de 56% et un taux de réponse à la diplopie à la semaine 15. Le médicament a généralement été bien toléré, avec 94% des patients ayant terminé le traitement.
Parmi les points forts, on note une réduction moyenne de 2,34 mm de la proptose, un taux de résolution complète de la diplopie de 32% et 54% des patients ayant atteint l'effet thérapeutique maximal sur le Score d'Activité Clinique. La société prévoit de soumettre une BLA dans la seconde moitié de 2025. Avec une position de trésorerie de 753 millions de dollars au mois de septembre 2024, Viridian dispose d'une marge de manœuvre jusqu'à la seconde moitié de 2027.
Viridian Therapeutics gab positive vorläufige Ergebnisse der THRIVE-2 Phase-3-Studie zu veligrotug bei chronischer Schilddrüsenaugenkrankheit (TED) bekannt. Die Studie erreichte alle primären und sekundären Endpunkte mit hoher statistischer Signifikanz und erzielte eine Proptose-Responder-Rate von 56% sowie eine Diplopie-Responder-Rate in der Woche 15. Das Medikament wurde im Allgemeinen gut vertragen, wobei 94% der Patienten die Behandlung abgeschlossen haben.
Wichtige Highlights sind eine durchschnittliche Reduktion der Proptose um 2,34 mm, eine vollständige Auflösungsrate der Diplopie von 32% und 54% der Patienten, die den maximalen therapeutischen Effekt auf dem klinischen Aktivitätsscore erreichen konnten. Das Unternehmen plant, in der zweiten Jahreshälfte 2025 einen BLA einzureichen. Mit einem Barguthaben von 753 Millionen Dollar zum September 2024 hat Viridian Spielraum bis zur zweiten Jahreshälfte 2027.
- Met all primary and secondary endpoints with statistical significance
- 56% proptosis responder rate (48% placebo-adjusted)
- 56% diplopia response rate (31% placebo-adjusted)
- 94% patient treatment completion rate
- Strong cash position of $753M providing runway through 2027
- BLA submission on track for H2 2025
- 9.6% placebo-adjusted rate of hearing impairment adverse events
Insights
The THRIVE-2 Phase 3 results represent a significant breakthrough in chronic Thyroid Eye Disease (TED) treatment. The trial demonstrated remarkable efficacy with a
The robust data package, showing consistent benefits across multiple endpoints including Clinical Activity Score reduction and overall response rate of
This clinical success significantly derisks Viridian's commercial prospects. The strong efficacy data in chronic TED, a currently underserved market, opens substantial revenue potential. The planned BLA submission in 2H 2025 could lead to commercialization by 2026, with the subcutaneous VRDN-003 program potentially following in 2027.
The company's healthy cash position of
- Veligrotug met all primary and secondary endpoints with high statistical significance in THRIVE-2, achieving a week 15 proptosis responder rate (PRR) of
- THRIVE-2 is the first global phase 3 study in patients with chronic TED to demonstrate a statistically significant and clinically meaningful
- Veligrotug was generally well-tolerated with
- BLA submission for veligrotug on track for second half of 2025; potential to transform the standard of care in TED with differentiated clinical profile demonstrated in the broadest population studied in a global phase 3 study across active and chronic TED patients to date -
- REVEAL-1 and REVEAL-2, global phase 3 clinical trials of subcutaneous VRDN-003 evaluating every four-week (Q4W) or every eight-week (Q8W) regimens, are both currently dosing and on track for topline data in 1H 2026; VRDN-003 is a half-life-extended anti-IGF-1R antibody with the same binding domain as veligrotug -
- Strong cash position of
- Conference call and webcast to be held today, December 16th at 8:00 a.m. ET -
“We are extremely pleased to announce better-than-expected THRIVE-2 results generated in the broadest population of chronic TED patients studied in a global phase 3 study to date. We believe that these efficacy and safety results in only five infusions, combined with our compelling data from THRIVE, confirm the potential of veli to be the treatment-of-choice for all forms of active and chronic TED,” said Steve Mahoney, Viridian’s President and CEO. “The robustness and consistency of our data, similar to THRIVE, showed strong and rapid responses in categories that we believe matter most to patients including proptosis reduction, diplopia resolution and improvements in Clinical Activity Scores. This is the first product candidate to demonstrate a diplopia response and resolution rate in a global chronic TED phase 3 study. Our BLA preparation work is underway, and, if approved, we now believe veli will offer a differentiated commercial product profile to patients. The combined results of THRIVE and THRIVE-2, give us even higher conviction that our subcutaneous VRDN-003 program will deliver positive topline data in the first half of 2026, which would enable a BLA submission in the second half of 2026.”
“These data represent an incredible step forward for TED patients. I’ve been treating TED for over 30 years, and these results in the broadest population of TED patients are highly encouraging. Resolving double vision or even improving it in chronic TED patients can really change their lives,” said Steven Leibowitz, M.D., Associate Clinical Professor of Ophthalmology, Stein Eye Institute, University of California Los Angeles and THRIVE-2 investigator. “I see veligrotug’s potential product profile as highly compelling with a rapid onset of treatment effect, diplopia benefit across a broad TED population, shorter dosing regimen, and favorable safety profile.”
THRIVE-2 Phase 3 Topline Results
THRIVE-2 Clinical Activity Data
THRIVE-2 met all primary and secondary endpoints at the 15-week primary analysis timepoint after five infusions of veligrotug, showing statistically significant responses on all of the measured signs and symptoms of TED: proptosis, CAS, and diplopia. THRIVE-2 enrolled a total of 188 patients, randomized to veligrotug (n = 125) and placebo (n = 63). The mean time since onset of TED in this patient population was 69.8 months.
The key data at the primary efficacy analysis timepoint of 15 weeks are as follows:
Proptosis:
-
Proptosis Responder Rate (PRR):
56% in veligrotug patients, compared with8% in placebo patients (48% placebo-adjusted, p < 0.0001). PRR was statistically significant at all time points, including as early as 3 weeks after just one infusion, demonstrating a rapid onset of response. PRR is defined as at least a 2-millimeter (mm) reduction in proptosis from baseline in the study eye without worsening in the fellow eye (≥ 2 mm increase), as measured by exophthalmometry. PRR results as measured by MRI/CT were consistent with those measured by exophthalmometry at the primary efficacy analysis timepoint. - Proptosis Mean Reduction: 2.34mm mean reduction in proptosis from baseline in veligrotug patients, compared with 0.46mm reduction in placebo patients (1.9mm placebo-adjusted, p < 0.0001).
Diplopia:
-
Diplopia Response:
56% of veligrotug patients achieved a diplopia response, compared with25% of placebo patients (31% placebo-adjusted, p = 0.0006). Rapid onset was observed as early as 6 weeks after just two infusions. Diplopia response is defined as patients achieving a reduction of at least 1 on the Gorman subjective diplopia scale at week 15, for those patients with diplopia at baseline (n = 102). -
Diplopia Complete Resolution:
32% of veligrotug patients achieved complete resolution of diplopia, compared with14% of placebo patients (18% placebo-adjusted, p = 0.0152). Rapid onset was observed as early as 6 weeks after just two infusions. Diplopia resolution is defined as patients achieving a score of 0 on the Gorman subjective diplopia scale at week 15, for those patients with diplopia at baseline.
Clinical Activity Score (CAS):
CAS measures inflammatory signs and symptoms of TED, providing a composite score of pain, as well as redness and swelling of the eyelids and conjunctiva, on a scale from 0 to 7.
-
CAS Reduction to 0 or 1:
54% of veligrotug patients achieved maximal or near-maximal therapeutic effect on CAS, compared with24% of placebo patients (29% placebo-adjusted, p = 0.006), defined as reaching a CAS of 0 or 1, among patients with a CAS of ≥ 3 at baseline (n = 104). - CAS Mean Reduction: 2.9-point mean reduction in CAS from baseline in veligrotug patients, compared with 1.3-point reduction in placebo patients (1.6-point placebo-adjusted, p < 0.0001), among patients with a CAS of ≥ 3 at baseline.
Overall Response:
-
Overall Responder Rate:
56% of veligrotug patients achieved an overall response, compared with7% of placebo patients (50% placebo-adjusted, p < 0.0001). Overall Responder Rate is defined as achieving a proptosis response without worsening of CAS from baseline (≥ 1 point increase) and without worsening in the fellow eye in either proptosis (2 mm increase) or CAS.
THRIVE-2 Safety Data
-
Generally Well-Tolerated: Veligrotug was generally well-tolerated with a safety profile consistent with previous veligrotug studies including THRIVE. The majority of adverse events (AEs) were mild, and
94% of veligrotug-treated patients completed their treatment course. -
Low Rate of Hearing Impairment: There was a
9.6% placebo-adjusted rate of hearing impairment AEs (12.8% incidence in veligrotug patients, compared with3.2% incidence in placebo patients).
“Seeing the strong data presented today demonstrating that diplopia can in fact be improved in patients with long standing chronic TED is exciting. Together with the robust activity in both THRIVE and THRIVE-2, favorable safety profile, and a shorter dosing regimen, we believe veli is positioned to become a market leading TED therapeutic,” said Tony Casciano, Chief Commercial Officer. “Veli has the potential to be the only approved therapy with data in chronic patients included in the labeling. We believe the strength and completeness of veli’s pivotal program, the largest to date in TED, could not only ensure advantageous market access, but also expand utilization in patients unaddressed by current therapies. Veli’s profile itself is inspiring, and if approved, our commercial team is eager to get veli to patients.”
Subcutaneous VRDN-003, a Potential Best-In-Class Anti-IGF-1R, On Track to Report Topline 1H 2026
VRDN-003 is an IGF-1R antibody with the same binding domain as veligrotug and is believed to be the only anti-IGF-1R in development with an extended half-life.
Based on this shared binding domain, Viridian believes the topline results from THRIVE-2, in addition to the previously reported THRIVE results, reinforces the potential best-in-class profile of VRDN-003 to deliver clinical activity and safety consistent with veligrotug in a low-volume, infrequent, self-administered, subcutaneous injection that patients take at home.
Viridian is currently dosing patients in two global phase 3 clinical trials for VRDN-003, REVEAL-1 and REVEAL-2, in active and chronic TED, respectively. Viridian anticipates reporting topline data from these studies in the first half of 2026 and submitting a BLA for VRDN-003 for the treatment of TED by year-end 2026.
Conference Call and Webcast Information
Viridian will host a conference call today at 8:00 a.m. ET to discuss the THRIVE-2 topline data. The dial-in number for the conference call is (800) 715-9871 for domestic participants and (646) 307-1963 for international participants. The conference ID is 9934051.
A live webcast of the conference call can be accessed through the “Events” page in the Investors section of the Viridian Therapeutics website. Following the live webcast, an archived version of the call will also be available on the website.
About Viridian Therapeutics
Viridian is a biopharmaceutical company focused on engineering and developing potential best-in-class medicines for patients with serious and rare diseases. Viridian’s expertise in antibody discovery and protein engineering enables the development of differentiated therapeutic candidates for previously validated drug targets in commercially established disease areas.
Viridian is advancing multiple candidates in the clinic for the treatment of patients with thyroid eye disease (TED). The company is conducting a pivotal program for veligrotug (VRDN-001), including two global phase 3 clinical trials (THRIVE and THRIVE-2), to evaluate its efficacy and safety in patients with active and chronic TED. Both THRIVE and THRIVE-2 reported positive topline data, meeting all the primary and secondary endpoints of each study. Viridian is also advancing VRDN-003 as a potential best-in-class subcutaneous therapy for the treatment of TED, including two ongoing global phase 3 pivotal clinical trials, REVEAL-1 and REVEAL-2, to evaluate the efficacy and safety of VRDN-003 in patients with active and chronic TED.
In addition to its TED portfolio, Viridian is advancing a novel portfolio of neonatal Fc receptor (FcRn) inhibitors, including VRDN-006 and VRDN-008, which has the potential to be developed in multiple autoimmune diseases.
Viridian is based in
Cautionary Note Regarding Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of words such as, but not limited to, “anticipate,” “believe,” “become,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “on track,” “plan,” “potential,” “predict,” “project,” “design,” “should,” “target,” “will,” or “would” or other similar terms or expressions that concern our expectations, plans and intentions. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations, and assumptions. Forward-looking statements include, without limitation, statements regarding: preclinical and clinical development of Viridian’s product candidates veligrotug (formerly VRDN-001), VRDN-003, VRDN-006 and VRDN-008; the anticipated VRDN-003 topline data from THRIVE-2 in the first half of 2026; anticipated BLA submissions for veligrotug in the second half of 2025 and VRDN-003 in the second half of 2026, pending data; Viridian’s expectation that its data package will support a BLA for VRDN-003; the potential utility, efficacy, potency, safety, clinical benefits, clinical response, convenience and number of indications of veligrotug, VRDN-003, VRDN-006 and VRDN-008; veligrotug’s potential to be a market-leading therapeutic and the only approved therapy with data in chronic patients included in the labeling; Viridian’s product candidates potentially being best-in-class; whether veligrotug will serve an unmet need; Viridian’s expectations regarding the potential commercialization of veligrotug and VRDN-003, if approved; and that Viridian’s cash, cash equivalents and short-term investments will be sufficient to fund its operations into the second half of 2027.
New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to: potential utility, efficacy, potency, safety, clinical benefits, clinical response and convenience of Viridian’s product candidates; that results or data from completed or ongoing clinical trials may not be representative of the results of ongoing or future clinical trials; that preliminary data may not be representative of final data; the timing, progress and plans for our ongoing or future research, preclinical and clinical development programs; changes to trial protocols for ongoing or new clinical trials; expectations and changes regarding the timing for regulatory filings; regulatory interactions expectations and changes regarding the timing for enrollment and data; uncertainty and potential delays related to clinical drug development; the duration and impact of regulatory delays in our clinical programs; the timing of and our ability to obtain and maintain regulatory approvals for our therapeutic candidates; manufacturing risks; competition from other therapies or products; estimates of market size; other matters that could affect the sufficiency of existing cash, cash equivalents and short-term investments to fund operations; our financial position and projected cash runway; our future operating results and financial performance; Viridian’s intellectual property position; the timing of preclinical and clinical trial activities and reporting results from same; that our product candidates may not be commercially successful, if approved and those risks set forth under the caption “Risk Factors” in our most recent quarterly report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 12, 2024 and other subsequent disclosure documents filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither the company, nor its affiliates, advisors, or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing the company’s views as of any date subsequent to the date hereof.
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Anabel Chan, 617-458-8725
Vice President, Investor Relations & Communications
IR@viridiantherapeutics.com
Louisa Stone, 617-272-4604
Manager, Investor Relations
IR@viridiantherapeutics.com
Source: Viridian Therapeutics, Inc.
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