– Investigational gene therapy fails to meet primary and secondary endpoints –
– Investor conference call and webcast Monday at 8:30 a.m. ET (5:30 a.m. PT) –
SAN DIEGO, CA, USA I April 26, 2015 I Celladon Corporation (CLDN) today announced that its Phase 2b CUPID2 trial did not meet its primary and secondary endpoints. CUPID2 is a randomized, double-blind, placebo-controlled, multinational trial evaluating a single, one-time, intracoronary infusion of the cardiovascular gene therapy agent MYDICAR(R) (AAV1/SERCA2a) versus placebo added to a maximal, optimized heart failure drug and device regimen.
In the study, the primary endpoint comparison of MYDICAR to placebo resulted in a hazard ratio of 0.93 (0.53, 1.65 95%CI) (p=0.81), defined as heart failure-related hospitalizations or ambulatory treatment for worsening heart failure. The secondary endpoint comparison of MYDICAR to placebo, defined as all-cause death, need for a mechanical circulatory support device, or heart transplant, likewise failed to show a significant treatment effect. The efficacy endpoint analyses were performed on the (n=243) modified intent to treat population (mITT), which excludes clinical events that occurred in patients who did not receive MYDICAR or placebo, or which occurred prior to dosing. All other exploratory efficacy endpoints (improvement in New York Heart Association classification, 6 Minute Walk Test, and Quality of Life) were also inconsistent with a treatment effect. No safety issues were noted.
“We are surprised and very disappointed that MYDICAR failed to meet the endpoints in the CUPID2 trial, and we are rigorously analyzing the data in an attempt to better understand the observed outcome. We would like to express our sincere gratitude to our investigators and patients who participated in the study,” said Krisztina Zsebo, Ph.D., CEO of Celladon. “At the same time we are evaluating our other programs in order to determine the best path forward to maximize shareholder value.”
“This trial was extremely well executed and adequately tested the hypothesis, but the therapy failed to achieve the primary and secondary endpoints. However, there were no safety issues,” said Barry Greenberg, M.D., FACC, Director, Advanced Heart Failure Treatment Program; Distinguished Professor of Medicine, University of California, San Diego, and the Chairman of the Executive Clinical Steering Committee of the CUPID2 trial.
About the CUPID2 Study
CUPID2 is a Phase 2b, randomized, double-blind, placebo-controlled, multinational trial evaluating a single intracoronary infusion of the cardiovascular gene therapy agent MYDICAR versus placebo added to a maximal, optimized heart failure regimen. The study included 250 adult patients who had stable NYHA (New York Heart Association) class II to IV ischemic or non-ischemic heart failure despite optimal therapy, reduced left ventricular ejection fraction (<= 35%) and a high risk for recurrent heart-failure hospitalizations. CUPID2 enrolled only patients with heart failure with reduced ejection fraction (HF-REF). The statistical analysis for the primary endpoint was performed on the modified intent to treat population (mITT), comprising all patients who, after randomization, underwent cardiac catheterization and drug or placebo administration.
The primary endpoint was time to recurrent heart failure related events (defined as heart failure-related hospitalizations or ambulatory treatment for worsening heart failure), using a statistical analysis methodology called joint frailty modeling. The secondary efficacy endpoint was time to first terminal event (defined as all-cause death, heart transplant or placement of a mechanical circulatory support device), analyzed simultaneously with the primary endpoint using joint frailty modeling.
About Celladon Corporation
Celladon is a clinical-stage biotechnology company applying its leadership position in the field of cardiovascular gene therapy to develop novel therapies for diseases with high unmet medical needs. Our lead programs target SERCA enzymes, which are a family of enzymes that play an integral part in the regulation of intra-cellular calcium in all human cells. Calcium dysregulation is implicated in a number of important and complex medical conditions and diseases, such as heart failure, vascular disease, diabetes and neurodegenerative diseases. The company conducts research and development on its mSCF gene therapy program for cardiac diseases. Celladon has also identified a number of potential first-in-class compounds addressing novel targets in diabetes and neurodegenerative diseases with its small molecule platform of SERCA2b modulators. For more information, please visit www.celladon.com.
SOURCE: Celladon
Post Views: 109
– Investigational gene therapy fails to meet primary and secondary endpoints –
– Investor conference call and webcast Monday at 8:30 a.m. ET (5:30 a.m. PT) –
SAN DIEGO, CA, USA I April 26, 2015 I Celladon Corporation (CLDN) today announced that its Phase 2b CUPID2 trial did not meet its primary and secondary endpoints. CUPID2 is a randomized, double-blind, placebo-controlled, multinational trial evaluating a single, one-time, intracoronary infusion of the cardiovascular gene therapy agent MYDICAR(R) (AAV1/SERCA2a) versus placebo added to a maximal, optimized heart failure drug and device regimen.
In the study, the primary endpoint comparison of MYDICAR to placebo resulted in a hazard ratio of 0.93 (0.53, 1.65 95%CI) (p=0.81), defined as heart failure-related hospitalizations or ambulatory treatment for worsening heart failure. The secondary endpoint comparison of MYDICAR to placebo, defined as all-cause death, need for a mechanical circulatory support device, or heart transplant, likewise failed to show a significant treatment effect. The efficacy endpoint analyses were performed on the (n=243) modified intent to treat population (mITT), which excludes clinical events that occurred in patients who did not receive MYDICAR or placebo, or which occurred prior to dosing. All other exploratory efficacy endpoints (improvement in New York Heart Association classification, 6 Minute Walk Test, and Quality of Life) were also inconsistent with a treatment effect. No safety issues were noted.
“We are surprised and very disappointed that MYDICAR failed to meet the endpoints in the CUPID2 trial, and we are rigorously analyzing the data in an attempt to better understand the observed outcome. We would like to express our sincere gratitude to our investigators and patients who participated in the study,” said Krisztina Zsebo, Ph.D., CEO of Celladon. “At the same time we are evaluating our other programs in order to determine the best path forward to maximize shareholder value.”
“This trial was extremely well executed and adequately tested the hypothesis, but the therapy failed to achieve the primary and secondary endpoints. However, there were no safety issues,” said Barry Greenberg, M.D., FACC, Director, Advanced Heart Failure Treatment Program; Distinguished Professor of Medicine, University of California, San Diego, and the Chairman of the Executive Clinical Steering Committee of the CUPID2 trial.
About the CUPID2 Study
CUPID2 is a Phase 2b, randomized, double-blind, placebo-controlled, multinational trial evaluating a single intracoronary infusion of the cardiovascular gene therapy agent MYDICAR versus placebo added to a maximal, optimized heart failure regimen. The study included 250 adult patients who had stable NYHA (New York Heart Association) class II to IV ischemic or non-ischemic heart failure despite optimal therapy, reduced left ventricular ejection fraction (<= 35%) and a high risk for recurrent heart-failure hospitalizations. CUPID2 enrolled only patients with heart failure with reduced ejection fraction (HF-REF). The statistical analysis for the primary endpoint was performed on the modified intent to treat population (mITT), comprising all patients who, after randomization, underwent cardiac catheterization and drug or placebo administration.
The primary endpoint was time to recurrent heart failure related events (defined as heart failure-related hospitalizations or ambulatory treatment for worsening heart failure), using a statistical analysis methodology called joint frailty modeling. The secondary efficacy endpoint was time to first terminal event (defined as all-cause death, heart transplant or placement of a mechanical circulatory support device), analyzed simultaneously with the primary endpoint using joint frailty modeling.
About Celladon Corporation
Celladon is a clinical-stage biotechnology company applying its leadership position in the field of cardiovascular gene therapy to develop novel therapies for diseases with high unmet medical needs. Our lead programs target SERCA enzymes, which are a family of enzymes that play an integral part in the regulation of intra-cellular calcium in all human cells. Calcium dysregulation is implicated in a number of important and complex medical conditions and diseases, such as heart failure, vascular disease, diabetes and neurodegenerative diseases. The company conducts research and development on its mSCF gene therapy program for cardiac diseases. Celladon has also identified a number of potential first-in-class compounds addressing novel targets in diabetes and neurodegenerative diseases with its small molecule platform of SERCA2b modulators. For more information, please visit www.celladon.com.
SOURCE: Celladon
Post Views: 109
