SAN DIEGO, July 7, 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 launched two new clinical development initiatives for MYDICAR®, its lead product candidate, in patients with end-stage renal disease (ESRD) undergoing surgery for arteriovenous fistula (AVF) creation in preparation for hemodialysis, and in advanced heart failure patients with systolic dysfunction that were previously excluded from MYDICAR trials due to pre-existing levels of neutralizing antibodies.
"We believe these new development initiatives will further increase the value of Celladon's pipeline and potentially allow us to broaden the clinical utility of MYDICAR for a wide range of patients," said Krisztina Zsebo, Ph.D., Chief Executive Officer of Celladon. "Early data underlying these initiatives have shown promising results and we look forward to understanding MYDICAR's potential in both additional settings."
Celladon plans to initiate a 100 patient Phase 2a trial with MYDICAR in ESRD patients undergoing surgery for AVF creation in preparation for hemodialysis. The trial will evaluate MYDICAR's effect on preventing neointimal hyperplasia and improving blood flow in treated vessels, as a means to enhance the AVF maturation process. AVF maturation failure is a common problem in approximately half of the patients that undergo the procedure. There are currently no U.S. Food and Drug Administration (FDA) approved products to enhance AVF maturation. Initial results from this study are expected in 2015.
The Company also plans to initiate a pilot, 24 patient, Phase 1/2 study of MYDICAR in advanced heart failure patients with systolic dysfunction that have been previously excluded from MYDICAR studies in this indication due to pre-existing levels of neutralizing antibodies against the AAV1 vector, which can block MYDICAR's activity. This study will examine whether plasma exchange can remove AAV1 neutralizing antibodies from the circulation in advance of MYDICAR administration. Based on Celladon's database of blood samples to date, the Company estimates that approximately 60 percent of all patients in the United States currently have AAV1 neutralizing antibodies. The Company expects to initiate this study in 2014, and initial results are expected in 2015.
In addition to these clinical trials, Celladon recently completed enrollment of the 250 patient Phase 2b CUPID2 trial evaluating the efficacy of MYDICAR in reducing the frequency of, or delaying heart failure-related hospitalizations. This randomized, double-blind, placebo-controlled, multinational trial is evaluating a single intracoronary infusion of MYDICAR versus placebo added to a maximal, optimized heart failure regimen in patients with New York Heart Association class III or IV symptoms of chronic heart failure due to systolic dysfunction. The Company has received "breakthrough designation" from the FDA for this MYDICAR program and expects to report results from this trial in April 2015.
About ESRD and AVFs
According to the United States Renal Data System, over 600,000 Americans suffered from ESRD as of the end of 2011. Patients with the disease often undergo surgery to create an AVF, a connection between an artery and a vein. AVFs are the preferred method for vascular access in ESRD patients who require life-saving maintenance hemodialysis because they provide greater blood flow and are associated with a lower mortality risk and complications such as infections, stenosis, and thrombosis than synthetic grafts or central venous catheters. However, vascular access has been called the achilles' heel of hemodialysis because of the poor outcomes following surgical placement AVFs. There are approximately 100,000 AVFs placed yearly in the United States, and approximately half of these fail to mature to a usable state, which results in patency loss. With patency loss, the AVF suffers from a significant reduction of blood flow. The clinical implications are severe and an episode of patency loss must be addressed urgently to restore blood flow and enable the patient to resume their life-saving dialysis treatment. AVF failure is typically caused by vessel injury that occurs during the surgical creation of the AVF, resulting in neointimal hyperplasia, or growth of tissues inside the vessels that results in vessel narrowing and reduced blood flow. There are currently no FDA approved products to enhance AVF maturation.
About Heart Failure
Heart failure is the inability of the heart to pump blood efficiently due to weakening and enlargement of the ventricles. Nearly six million individuals are currently diagnosed with heart failure in the United States according to the American Heart Association (AHA). Despite optimal guideline-directed therapies employing a wide range of pharmacologic, device and surgical options, many heart failure patients deteriorate over time. The long-term prognosis associated with heart failure is worse than that associated with the majority of cancers, with a mortality rate of approximately 50 percent at five years following initial diagnosis. In the United States, over one million primary heart failure-related hospitalizations and over 280,000 heart failure-related deaths occur annually. The one- and six-month readmission rates after heart failure-related hospitalization are close to 25 and 50 percent, respectively, and there is growing pressure on hospitals to reduce readmissions for heart failure. According to a recently published review article in Journal Clinical Cardiology, the estimated direct cost of heart failure in the United States in 2012 was greater than $60 billion, over half of which was related to repeated hospitalizations.
In patients with heart failure, SERCA2a, an enzyme critical to the contraction of the cardiac muscle cell, becomes deficient. Numerous human studies have established a clear association between depleted SERCA2a enzyme in cardiac cells and the progression of end-stage heart failure.
Celladon is a clinical-stage biotechnology company applying its leadership position in the field of calcium dysregulation by targeting SERCA enzymes to develop novel therapies for diseases with tremendous unmet medical needs. 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, vascular disease, diabetes and neurodegenerative diseases. MYDICAR, the Company's most advanced product candidate, uses gene therapy to target SERCA2a, which is an enzyme that becomes deficient in patients with heart failure. In addition, Celladon has 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.
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 MYDICAR's potential utility in improving the rate of AVF maturation in ESRD patients, the potential for plasma exchange to increase the number of systolic heart failure patients who may be eligible for MYDICAR therapy, as well as Celladon's expectations around the timing for initiating planned clinical trials and reporting results from ongoing and future clinical trials. 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 Form 10-Q for the quarter ended March 31, 2014. 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.
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