SAN DIEGO, March 4, 2014 (GLOBE NEWSWIRE) -- Celladon Corporation (Nasdaq:CLDN), a clinical-stage biotechnology company focused on developing novel therapies by applying its leadership position in the field of SERCA enzymes, today announced it has completed enrollment and randomized 250 patients in the phase 2b trial titled "Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease," known as CUPID 2, which is evaluating the efficacy and safety of MYDICAR (AAV1/SERCA2a) in patients with NYHA class III/IV symptoms of systolic heart failure.
"The completion of enrollment in the CUPID 2 trial marks significant progress in the development of MYDICAR for patients with advanced heart failure and brings us one step closer to offering this important therapy to patients," said Krisztina Zsebo, Ph.D., President and Chief Executive Officer of Celladon Corporation. "We now look forward to April 2015, when we anticipate being able to report results from this important trial."
The CUPID 2 trial is a multinational, multicenter, double-blind, placebo-controlled, randomized trial of a single intracoronary infusion of high-dose MYDICAR (1 x 1013 DRP) versus placebo added to a maximal, optimized heart failure regimen. The primary objective is to determine the efficacy of MYDICAR in patients with ischemic or non-ischemic cardiomyopathy and advanced symptoms of heart failure by reducing the frequency and/or delaying heart failure-related hospitalizations compared to placebo-treated patients. Secondary objectives include assessment of terminal events, such as death, need for a ventricular assist device, or heart transplant. In addition, the safety of MYDICAR will be determined by assessing the incidence and severity of adverse events and changes in laboratory parameters.
"The fact that heart failure patients remain at significant risk for clinical deterioration over time, despite receiving maximal, optimized therapy with currently available drugs and devices, emphasizes the strong unmet need for new treatment options for these patients," said Barry Greenberg, M.D., FACC, Director, Advanced Heart Failure Treatment Program; Professor of Medicine, University of California, San Diego, and the Chairman of the Executive Clinical Steering Committee of the CUPID 2 trial. "Should the CUPID 2 trial show similar results to previous trials and subsequently result in approval of MYDICAR by regulatory authorities, I believe MYDICAR could play a significant role in improving the clinical course of heart failure patients."
Celladon has obtained a Special Protocol Assessment (SPA), whereby the U.S. Food and Drug Administration (FDA) has agreed to use time-to-multiple heart failure-related hospitalizations in the presence of terminal events (all-cause death, heart transplant, LVAD implantation) as the primary efficacy endpoint for a MYDICAR phase 3 pivotal trial. The CUPID 2 trial uses a similar clinical protocol with identical endpoints as agreed to in the SPA.
Celladon has received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the CUPID 2 trial. In November 2013, the EMA indicated that if MYDICAR demonstrates a substantial and highly significant treatment effect in the advanced heart failure population, and no untoward effects attributable to MYDICAR are observed, a safety database of approximately 205-230 subjects may be sufficient for a safety assessment to allow for acceptance of a Marketing Authorization Application for MYDICAR for the treatment of systolic heart failure. Celladon therefore believes that, if the above conditions are met, a phase 3 trial may not be required for marketing approval in Europe.
CUPID 1 Trial Results
The CUPID 1 trial was a Phase 2a clinical trial of a single intracoronary infusion of high-dose MYDICAR in patients with advanced heart failure. In this 39-patient trial, MYDICAR was found to be safe and well-tolerated, reduced heart failure-related hospitalizations, improved patients' symptoms and quality of life, and improved key markers of cardiac function predictive of survival, such as elevated levels of natriuretic peptides and left ventricular end systolic volume. Three dose levels of MYDICAR were administered, and the high-dose MYDICAR group met the primary endpoint versus placebo at six months, and all positive trends were confirmed at 12 months. Recurrent cardiovascular events were adjudicated by a blinded clinical endpoint committee and included worsening heart failure (either hospitalization or treatment with intravenous diuretics, vasodilators or positive inotropes; mechanical fluid removal; or intra-aortic balloon pump) and myocardial infarctions. The hazard ratio at 12 months for the high-dose MYDICAR group versus placebo for recurrent cardiovascular events in the presence of terminal events (LVAD, heart transplant, cardiovascular death) was 0.12 (p=0.003) representing a risk reduction of 88% with MYDICAR versus placebo. In November 2013, the long term follow-up results from the CUPID 1 trial were presented at the American Heart Association annual meeting. In the additional two year follow up period of the CUPID 1 trial, the durability of reduced cardiovascular and terminal events previously observed in the MYDICAR high-dose cohort at 12 months was maintained. The risk of recurrent cardiovascular events in the presence of terminal events through full three years of follow up was reduced by 82% in the high‑dose group compared to the placebo group (p=0.048). Terminal and recurrent CV events captured in Long-Term Follow-Up were limited to death, heart transplant, LVAD implantation and worsening HF, and were not adjudicated. No safety concerns were noted during the three year follow-up period.
We are a clinical-stage biotechnology company applying our leadership position in the field of calcium dysregulation by targeting SERCA enzymes to develop novel therapies for diseases with tremendous unmet medical needs. Sarco/endoplasmic reticulum Ca2+-ATPase, or SERCA, enzymes 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, which is a clinical syndrome characterized by poor heart function, resulting in inadequate blood flow to meet the body's metabolic needs, as well as diabetes and neurodegenerative diseases. Our therapeutic portfolio for diseases characterized by SERCA enzyme deficiency includes both gene therapies and small molecule compounds. MYDICAR, our most advanced product candidate, uses gene therapy to target SERCA2a, which is an enzyme that becomes deficient in patients with heart failure. In addition, we have identified a number of potential first-in-class compounds addressing novel targets in diabetes and neurodegenerative diseases with our small molecule platform of SERCA2b modulators.
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements regarding Celladon's anticipated timing for reporting results from CUPID 2, the extent of the role MYDICAR may have in improving the clinical course of heart failure patients, and whether a phase 3 trial for MYDICAR will be required by applicable regulatory authorities. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon Celladon's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with the process of conducting product development activities and clinical trials and obtaining regulatory approval to commercialize product candidates, our reliance on third parties, the need to raise additional funding when needed in order to conduct our business, and the degree of market acceptance of MYDICAR by physicians, patients, third-party payors and others in the medical community. These and other risks and uncertainties are described more fully in Celladon's filings with the Securities and Exchange Commission, including without limitation its Registration Statement on Form S-1 that was originally filed with the Securities and Exchange Commission on October 10, 2013, and the amendments thereto. All forward-looking statements contained in this press release speak only as of the date on which they were made. Celladon undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Fredrik Wiklund Vice President, Corporate Development and Investor Relations (858) 432-7215
San Diego, California, UNITED STATES
Fredrik Wiklund Vice President, Corporate Development and Investor Relations (858) 432-7215
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