Celladon Corporation Announces Trial To Investigate MYDICAR In Patients With Heart Failure And LVAD
8/11/2014 11:59:54 AM
SAN DIEGO, Aug. 11, 2014 -- Celladon Corporation (Nasdaq:CLDN), a clinical-stage biotechnology company applying its leadership position in the field of gene therapy and calcium dysregulation, today announced that the first patient has been dosed in a clinical trial titled "Investigation of the Safety and Feasibility of AAV1/SERCA2a Gene Transfer in Patients with Heart Failure and a Left Ventricular Assist Device (LVAD)," which is designed to assess the potential utility of MYDICAR in advanced heart failure patients whose hearts are being supported by LVADs. This trial is partially funded by the British Heart Foundation and sponsored by Imperial College London.
"The initiation of this trial highlights the potential for MYDICAR to positively impact a wide range of cardiovascular conditions," said Krisztina Zsebo, Ph.D., Chief Executive Officer of Celladon. "The LVAD patient population has exhausted existing pharmaceutical and device treatment options. We believe MYDICAR may serve as a valuable, and much needed, new treatment modality for these very advanced heart failure patients."
Dr. Alex Lyon, the trial's lead investigator from Imperial College London's National Heart and Lung Institute and honorary consultant cardiologist at Royal Brompton & Harefield NHS Foundation Trust, said, "This is the first time patients with heart failure and LVADS have received cardiac gene therapy. We will be evaluating safety in this new patient group and signals of benefit on heart function, given they are a patient group in need of new treatment options. Uniquely, we will be taking a heart muscle biopsy from each patient to measure the levels of treatment gene DNA delivered to their heart, and whether the presence of AAV neutralizing antibodies interferes with the efficiency of gene delivery. We hope our trial will provide important new information to guide the development of cardiac gene therapy as a new treatment paradigm for our patients with heart failure, including those with LVADs."
This proof-of-concept study is expected to evaluate 24 patients with varying levels of neutralizing antibodies to determine the safety and feasibility of using MYDICAR to treat advanced heart failure patients with LVADs, how well MYDICAR delivers the gene for SERCA2a to heart cells and the impact of circulating neutralizing antibodies to AAV1 on the ability of MYDICAR to deliver the SERCA2a gene to heart muscle cells. Of the patients enrolled in the study, 16 will be treated with MYDICAR and eight will be treated with placebo. Safety data and changes in heart function as assessed by tissue Doppler echocardiography, six-minute walk tests, cardiopulmonary exercise and metabolic stress tests will be collected and analyzed. In addition, as an exploratory sub-study, patients will be assessed to see whether their cardiac function improves enough to support being potentially weaned off their LVADs. Six months post-treatment, all patients will undergo a heart biopsy for collection of tissue to determine the presence of the SERCA2a gene.
Additionally, Celladon recently completed enrollment of a 250-patient Phase 2b CUPID2 clinical trial evaluating the efficacy of MYDICAR in reducing the frequency of, or delaying of, heart failure-related hospitalizations. This randomized, double-blind, placebo-controlled, multinational trial is evaluating a single intracoronary infusion of high-dose MYDICAR versus placebo, added to a maximal, optimized heart failure regimen in patients with New York Heart Association (NYHA) class III or IV symptoms of chronic heart failure due to systolic dysfunction. The Company has received Breakthrough Therapy designation from the U.S. Food and Drug Administration for this program and expects to report results from this clinical trial in April 2015.
LVADs are battery operated mechanical circulatory devices used to partially or completely replace the function of the left ventricle of the heart for advanced heart failure patients awaiting a heart transplant, or as a destination therapy for patients with NYHA Class IV heart failure who will never receive a heart transplant. Given that the circulatory system of a patient is dependent on these devices, device failure usually translates into a catastrophic event for the patient. The implantation of an LVAD requires invasive open-chest surgery and can potentially result in a host of complications, such as thrombosis and infection, which can make LVADs undesirable for many patients.
MYDICAR uses gene therapy to selectively target and restore SERCA2a enzyme levels by transferring the SERCA2a gene directly into cardiac muscle cells, which can improve the heart's ability to pump blood. MYDICAR utilizes a non-pathogenic recombinant adeno-associated virus (AAV) and is delivered directly to the heart in a routine outpatient procedure, similar to an angiogram, in a cardiac catheterization laboratory.
Results of a 39-patient Phase 2a CUPID 1 clinical trial of a single intracoronary infusion of high-dose MYDICAR in patients with advanced heart failure due to a systolic dysfunction showed the therapy was safe and well-tolerated in the study. In the Phase 2a CUPID 1 clinical trial, MYDICAR reduced heart failure-related hospitalizations and improved patients' symptoms, quality of life and key markers of cardiac function predictive of survival, such as elevated levels of natriuretic peptides and left ventricular end systolic volume. Long-term follow-up results from the Phase 2a CUPID 1 clinical trial showed that in the additional two-year follow-up period, 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 over three years of follow up was reduced by 82 percent in the high-dose group compared with the placebo group (p=0.048). No safety concerns were noted during the three-year follow-up period for patients who received MYDICAR.
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. 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, 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, 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.
About Celladon Corporation
Celladon is a clinical-stage biotechnology company applying its leadership position in the field of gene therapy and calcium dysregulation to develop novel therapies for diseases with tremendous 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. 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. Celladon recently completed enrollment of a 250-patient Phase 2b CUPID2 clinical trial evaluating the efficacy of MYDICAR in reducing the frequency of, or delaying of, heart failure-related hospitalizations. This randomized, double-blind, placebo-controlled, multinational trial is evaluating a single intracoronary infusion of high-dose MYDICAR versus placebo, added to a maximal, optimized heart failure regimen in patients with NYHA class III or IV symptoms of chronic heart failure due to systolic dysfunction. The Company has received Breakthrough Therapy designation from the FDA for this MYDICAR program and expects to report results from the Phase 2b CUPID2 clinical trial in April 2015. 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, references to the potential proof-of-concept outcome of the clinical trial in advanced heart failure patients whose hearts are being supported by LVADs; the potential for MYDICAR to have a positive impact on a wide range of cardiovascular conditions and to potentially serve as a new treatment modality for the LVAD patient population; the planned design of the LVAD clinical trial; and expected timing for receipt of data from ongoing 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 June 30, 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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