– Veligrotug (VRDN-001) achieved all primary and secondary endpoints in THRIVE, the largest phase 3 trial conducted to date of an anti-IGF-1R antibody in thyroid eye disease (TED), with a week 15 proptosis responder rate (PRR) of 70% and a placebo-adjusted PRR of 64% (p < 0.0001) –
– All secondary endpoints were highly statistically significant (p < 0.0001), with clinically meaningful patient outcomes, including complete resolution of diplopia in 54% of patients (placebo-adjusted rate of 43%) and reduction of Clinical Activity Score (CAS) to 0 or 1 in 64% of patients (placebo-adjusted reduction of 46%) treated with veligrotug –
– Veligrotug was generally well-tolerated with no treatment-related serious adverse events (SAEs), and a 5.5% placebo-adjusted rate of hearing impairment AEs –
– THRIVE-2 study of veligrotug in patients with chronic TED fully enrolled with topline data readout on track for year-end 2024; BLA submission anticipated in second half of 2025, as planned –
– REVEAL-1 and REVEAL-2, global phase 3 trials of VRDN-003 dosed every four (Q4W) or eight weeks (Q8W), initiated in August; VRDN-003 is a subcutaneous, half-life-extended anti-IGF-1R antibody with the same binding domain as veligrotug –
– Cash, cash equivalents, and short-term investments of $571.4 million as of June 30, 2024; provides cash runway into the second half of 2026, beyond the planned veligrotug BLA submission, expected REVEAL topline data, and multiple anticipated readouts from Viridian’s FcRn inhibitor programs –
WALTHAM, MA, USA I September 10, 2024 I Viridian Therapeutics, Inc. (NASDAQ: VRDN), a biopharmaceutical company focused on discovering and developing potential best-in-class medicines for serious and rare diseases, today announced positive topline data from the THRIVE phase 3 clinical trial of VRDN-001, now known as veligrotug, an intravenously delivered anti-insulin-like growth factor-1 receptor (IGF-1R) antibody, in patients with active thyroid eye disease (TED). TED is an autoimmune condition characterized by inflammation, growth, and damage to tissues around and behind the eyes.
“We are thrilled to see these exciting THRIVE topline results which met our high bars for both efficacy and safety. We were particularly pleased to observe the rapid onset of clinically meaningful responses across all endpoints, and veligrotug’s safety profile exceeded our expectations. Veligrotug utilizes a differentiated, abbreviated five infusion 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,” said Steve Mahoney, Viridian’s President and CEO. “Our excitement with the THRIVE results extends well beyond veligrotug to the other half of our clinical TED franchise, subcutaneously administered VRDN-003, for which we initiated two phase 3 clinical trials last month. We believe veligrotug and VRDN-003 have the potential to become the preferred treatments for TED patients. Further, the strong THRIVE results reinforce our confidence in VRDN-003, which shares the same binding domain as veligrotug, as a potential best-in-class infrequent subcutaneous injection that we believe will be transformative for TED patients and expand the market. Our team has executed extremely effectively with both THRIVE and THRIVE-2, exceeding enrollment targets in both studies and across geographies including in the United States, which gives us confidence that we will swiftly enroll the VRDN-003 trials, REVEAL-1 and REVEAL-2. In addition to our TED franchise, we are excited about our emerging FcRn inhibitor portfolio that we look forward to discussing more later this year.”
“These phase 3 clinical data demonstrate the robust clinical activity of veligrotug. The data showed substantial improvements in proptosis, clinical activity score, and diplopia in patients with TED after just five infusions, and these strong results are consistent with the clinical outcomes of IGF-1R antagonism in TED. Veligrotug also showed a rapid onset of action which I believe is meaningful for patients,” said Michael Yen, M.D., an investigator in THRIVE and Professor of Oculoplastic Surgery and Ophthalmology, at Baylor College of Medicine. “Veligrotug showed a favorable safety profile in a large phase 3 clinical trial that closely monitored safety, including the potential for hearing impairment. As a THRIVE investigator, I am excited to see these results and look forward to the REVEAL clinical trials for VRDN-003 to help bring additional potential treatment options for patients living with TED.”
VRDN-001 THRIVE Phase 3 Topline Results
THRIVE Clinical Activity Data
THRIVE met the primary and all secondary endpoints at 15 weeks after five infusions of veligrotug, showing highly statistically significant (p < 0.0001) improvements on all of the measured signs and symptoms of TED. Veligrotug additionally showed a rapid onset of action, with the majority (53%) of veligrotug-treated patients achieving a proptosis response after just 1 infusion, or 3 weeks after start of therapy. THRIVE enrolled 113 patients, randomized to veligrotug (n=75) and placebo (n=38).
Patients receiving veligrotug had statistically significant and clinically meaningful improvements across the following key disease endpoints at the primary efficacy analysis timepoint of 15 weeks:
Proptosis:
- Proptosis Responder Rate: 70% proptosis responder rate (PRR) in patients receiving veligrotug, compared with 5% of patients receiving placebo (64% placebo-adjusted) (p < 0.0001). 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.
- Proptosis Mean Reduction: 2.9 mm mean reduction in proptosis from baseline in patients receiving veligrotug, compared with 0.5mm reduction in patients receiving placebo (2.4mm placebo-adjusted) (p < 0.0001), as measured by exophthalmometry.
Diplopia:
- Diplopia Complete Resolution: 54% complete resolution of diplopia in patients receiving veligrotug, compared with 12% of patients receiving placebo (43% placebo-adjusted) (p < 0.0001). Diplopia resolution is defined by patients achieving a score of 0 on the Gorman subjective diplopia scale at week 15, among patients with diplopia at baseline (n=76).
- Diplopia Response: 63% achieved a diplopia response in patients receiving veligrotug, compared with 20% of patients receiving placebo (43% placebo-adjusted) (p < 0.0001). Diplopia response is defined by patients achieving a reduction of at least 1 on the Gorman subjective diplopia scale at week 15, among patients with diplopia at baseline.
Clinical Activity Score (CAS):
- CAS Reduction to 0 or 1: 64% of patients receiving veligrotug achieved maximal or near-maximal therapeutic effect on CAS, compared with 18% of patients receiving placebo (46% placebo-adjusted) (p < 0.0001), defined as reaching a CAS of 0 or 1. 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 Mean Reduction: 3.4-point mean reduction in CAS from baseline for patients receiving veligrotug, compared with 1.7-point reduction in patients receiving placebo (1.7-point placebo-adjusted) (p < 0.0001).
Overall Response:
- Overall Responder Rate: 67% of patients receiving veligrotug achieved an overall response, compared with 5% of patients receiving placebo (61% placebo-adjusted) (p < 0.0001). Overall Responder Rate is defined as achieving 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).
THRIVE Safety Data
- Generally Well-Tolerated: Veligrotug was generally well-tolerated with a safety profile consistent with previous veligrotug studies. The majority of adverse events (AEs) were mild, and there was a low rate (4%) of discontinuations in the veligrotug arm. There were no treatment-related serious AEs.
- Low Rate of Hearing Impairment: There was a 5.5% placebo-adjusted rate of hearing impairment AEs in THRIVE (16% incidence in patients receiving veligrotug, compared with 10.5% incidence in patients receiving placebo).
Veligrotug: On-Track to Submit Biologics License Application (BLA) in Second Half of 2025
The second phase 3 clinical trial of veligrotug, THRIVE-2, in patients with chronic TED is ongoing. Viridian completed enrollment of THRIVE-2 in July 2024, and topline data readout is on track for year-end 2024. Viridian anticipates submitting a BLA for veligrotug for the treatment of TED in 2H 2025, as planned.
VRDN-003 REVEAL Clinical Trials Initiated in August; Potential Best-in-Class Program on Track for BLA Submission by Year-end 2026, Approximately One Year After Veligrotug BLA Submission
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.
Viridian believes these topline results from THRIVE provide strong support for a potential best-in-class profile of VRDN-003, with the potential to deliver clinical efficacy and safety consistent with veligrotug in a low-volume, infrequent, self-administered, subcutaneous injection that patients take at home.
Viridian initiated two global phase 3 clinical trials for VRDN-003 in August as planned: REVEAL-1 and REVEAL-2 in active and chronic TED, respectively. Both trials will evaluate VRDN-003 subcutaneously administered every Q4W or Q8W and will assess outcomes versus placebo. Viridian anticipates topline data from both trials in the first half of 2026, with a BLA submission 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 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 8636908.
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. 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 Waltham, Massachusetts. For more information, please visit www.viridiantherapeutics.com. Follow Viridian on LinkedIn and X.
SOURCE: Viridian Therapeutics
Post Views: 1,986
– Veligrotug (VRDN-001) achieved all primary and secondary endpoints in THRIVE, the largest phase 3 trial conducted to date of an anti-IGF-1R antibody in thyroid eye disease (TED), with a week 15 proptosis responder rate (PRR) of 70% and a placebo-adjusted PRR of 64% (p < 0.0001) –
– All secondary endpoints were highly statistically significant (p < 0.0001), with clinically meaningful patient outcomes, including complete resolution of diplopia in 54% of patients (placebo-adjusted rate of 43%) and reduction of Clinical Activity Score (CAS) to 0 or 1 in 64% of patients (placebo-adjusted reduction of 46%) treated with veligrotug –
– Veligrotug was generally well-tolerated with no treatment-related serious adverse events (SAEs), and a 5.5% placebo-adjusted rate of hearing impairment AEs –
– THRIVE-2 study of veligrotug in patients with chronic TED fully enrolled with topline data readout on track for year-end 2024; BLA submission anticipated in second half of 2025, as planned –
– REVEAL-1 and REVEAL-2, global phase 3 trials of VRDN-003 dosed every four (Q4W) or eight weeks (Q8W), initiated in August; VRDN-003 is a subcutaneous, half-life-extended anti-IGF-1R antibody with the same binding domain as veligrotug –
– Cash, cash equivalents, and short-term investments of $571.4 million as of June 30, 2024; provides cash runway into the second half of 2026, beyond the planned veligrotug BLA submission, expected REVEAL topline data, and multiple anticipated readouts from Viridian’s FcRn inhibitor programs –
WALTHAM, MA, USA I September 10, 2024 I Viridian Therapeutics, Inc. (NASDAQ: VRDN), a biopharmaceutical company focused on discovering and developing potential best-in-class medicines for serious and rare diseases, today announced positive topline data from the THRIVE phase 3 clinical trial of VRDN-001, now known as veligrotug, an intravenously delivered anti-insulin-like growth factor-1 receptor (IGF-1R) antibody, in patients with active thyroid eye disease (TED). TED is an autoimmune condition characterized by inflammation, growth, and damage to tissues around and behind the eyes.
“We are thrilled to see these exciting THRIVE topline results which met our high bars for both efficacy and safety. We were particularly pleased to observe the rapid onset of clinically meaningful responses across all endpoints, and veligrotug’s safety profile exceeded our expectations. Veligrotug utilizes a differentiated, abbreviated five infusion 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,” said Steve Mahoney, Viridian’s President and CEO. “Our excitement with the THRIVE results extends well beyond veligrotug to the other half of our clinical TED franchise, subcutaneously administered VRDN-003, for which we initiated two phase 3 clinical trials last month. We believe veligrotug and VRDN-003 have the potential to become the preferred treatments for TED patients. Further, the strong THRIVE results reinforce our confidence in VRDN-003, which shares the same binding domain as veligrotug, as a potential best-in-class infrequent subcutaneous injection that we believe will be transformative for TED patients and expand the market. Our team has executed extremely effectively with both THRIVE and THRIVE-2, exceeding enrollment targets in both studies and across geographies including in the United States, which gives us confidence that we will swiftly enroll the VRDN-003 trials, REVEAL-1 and REVEAL-2. In addition to our TED franchise, we are excited about our emerging FcRn inhibitor portfolio that we look forward to discussing more later this year.”
“These phase 3 clinical data demonstrate the robust clinical activity of veligrotug. The data showed substantial improvements in proptosis, clinical activity score, and diplopia in patients with TED after just five infusions, and these strong results are consistent with the clinical outcomes of IGF-1R antagonism in TED. Veligrotug also showed a rapid onset of action which I believe is meaningful for patients,” said Michael Yen, M.D., an investigator in THRIVE and Professor of Oculoplastic Surgery and Ophthalmology, at Baylor College of Medicine. “Veligrotug showed a favorable safety profile in a large phase 3 clinical trial that closely monitored safety, including the potential for hearing impairment. As a THRIVE investigator, I am excited to see these results and look forward to the REVEAL clinical trials for VRDN-003 to help bring additional potential treatment options for patients living with TED.”
VRDN-001 THRIVE Phase 3 Topline Results
THRIVE Clinical Activity Data
THRIVE met the primary and all secondary endpoints at 15 weeks after five infusions of veligrotug, showing highly statistically significant (p < 0.0001) improvements on all of the measured signs and symptoms of TED. Veligrotug additionally showed a rapid onset of action, with the majority (53%) of veligrotug-treated patients achieving a proptosis response after just 1 infusion, or 3 weeks after start of therapy. THRIVE enrolled 113 patients, randomized to veligrotug (n=75) and placebo (n=38).
Patients receiving veligrotug had statistically significant and clinically meaningful improvements across the following key disease endpoints at the primary efficacy analysis timepoint of 15 weeks:
Proptosis:
- Proptosis Responder Rate: 70% proptosis responder rate (PRR) in patients receiving veligrotug, compared with 5% of patients receiving placebo (64% placebo-adjusted) (p < 0.0001). 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.
- Proptosis Mean Reduction: 2.9 mm mean reduction in proptosis from baseline in patients receiving veligrotug, compared with 0.5mm reduction in patients receiving placebo (2.4mm placebo-adjusted) (p < 0.0001), as measured by exophthalmometry.
Diplopia:
- Diplopia Complete Resolution: 54% complete resolution of diplopia in patients receiving veligrotug, compared with 12% of patients receiving placebo (43% placebo-adjusted) (p < 0.0001). Diplopia resolution is defined by patients achieving a score of 0 on the Gorman subjective diplopia scale at week 15, among patients with diplopia at baseline (n=76).
- Diplopia Response: 63% achieved a diplopia response in patients receiving veligrotug, compared with 20% of patients receiving placebo (43% placebo-adjusted) (p < 0.0001). Diplopia response is defined by patients achieving a reduction of at least 1 on the Gorman subjective diplopia scale at week 15, among patients with diplopia at baseline.
Clinical Activity Score (CAS):
- CAS Reduction to 0 or 1: 64% of patients receiving veligrotug achieved maximal or near-maximal therapeutic effect on CAS, compared with 18% of patients receiving placebo (46% placebo-adjusted) (p < 0.0001), defined as reaching a CAS of 0 or 1. 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 Mean Reduction: 3.4-point mean reduction in CAS from baseline for patients receiving veligrotug, compared with 1.7-point reduction in patients receiving placebo (1.7-point placebo-adjusted) (p < 0.0001).
Overall Response:
- Overall Responder Rate: 67% of patients receiving veligrotug achieved an overall response, compared with 5% of patients receiving placebo (61% placebo-adjusted) (p < 0.0001). Overall Responder Rate is defined as achieving 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).
THRIVE Safety Data
- Generally Well-Tolerated: Veligrotug was generally well-tolerated with a safety profile consistent with previous veligrotug studies. The majority of adverse events (AEs) were mild, and there was a low rate (4%) of discontinuations in the veligrotug arm. There were no treatment-related serious AEs.
- Low Rate of Hearing Impairment: There was a 5.5% placebo-adjusted rate of hearing impairment AEs in THRIVE (16% incidence in patients receiving veligrotug, compared with 10.5% incidence in patients receiving placebo).
Veligrotug: On-Track to Submit Biologics License Application (BLA) in Second Half of 2025
The second phase 3 clinical trial of veligrotug, THRIVE-2, in patients with chronic TED is ongoing. Viridian completed enrollment of THRIVE-2 in July 2024, and topline data readout is on track for year-end 2024. Viridian anticipates submitting a BLA for veligrotug for the treatment of TED in 2H 2025, as planned.
VRDN-003 REVEAL Clinical Trials Initiated in August; Potential Best-in-Class Program on Track for BLA Submission by Year-end 2026, Approximately One Year After Veligrotug BLA Submission
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.
Viridian believes these topline results from THRIVE provide strong support for a potential best-in-class profile of VRDN-003, with the potential to deliver clinical efficacy and safety consistent with veligrotug in a low-volume, infrequent, self-administered, subcutaneous injection that patients take at home.
Viridian initiated two global phase 3 clinical trials for VRDN-003 in August as planned: REVEAL-1 and REVEAL-2 in active and chronic TED, respectively. Both trials will evaluate VRDN-003 subcutaneously administered every Q4W or Q8W and will assess outcomes versus placebo. Viridian anticipates topline data from both trials in the first half of 2026, with a BLA submission 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 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 8636908.
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. 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 Waltham, Massachusetts. For more information, please visit www.viridiantherapeutics.com. Follow Viridian on LinkedIn and X.
SOURCE: Viridian Therapeutics
Post Views: 1,986
