Celladon Receives Breakthrough Therapy Designation From FDA for MYDICAR

Celladon Corporation

, a clinical-stage biotechnology company developing novel therapies for patients with heart failure and other diseases characterized by SERCA enzyme deficiencies, today announced that its lead product candidate, MYDICAR®, has been granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for reducing hospitalizations for heart failure in NYHA class III or IV chronic heart failure patients who are NAb negative. This designation is intended to expedite the development and review of drugs for serious or life-threatening conditions and where preliminary clinical evidence suggests it provides a substantial improvement over existing therapies. Celladon is developing MYDICAR as a novel, first-in-class therapy for patients with chronic heart failure due to systolic dysfunction. MYDICAR uses genetic enzyme replacement therapy to correct the deficiency in the enzyme SERCA2a, which is an enzyme that becomes deficient in heart failure patients and results in inadequate pumping of the heart. Celladon has developed a companion diagnostic to identify the patients who are AAV1 NAb negative and therefore eligible for MYDICAR treatment. "We are looking forward to working with the senior staff at the FDA to determine the most expeditious path to bring MYDICAR to patients with advanced heart failure. This breakthrough therapy designation validates MYDICAR's unique characteristics and clinical data to date and underscores the urgent need for new treatments for heart failure," said Krisztina Zsebo, Ph.D., president and CEO of Celladon. "MYDICAR has the potential to provide transformative disease-modifying effects with long-term benefits in heart failure patients with a single administration. Our goal is to bring MYDICAR to market as quickly as possible in the United States, where we estimate approximately 350,000 heart failure patients with currently limited remaining treatment options could be eligible for therapy." Celladon is currently evaluating MYDICAR in the Phase 2b CUPID 2 trial to determine its efficacy in reducing the frequency of and/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 NYHA class III or IV symptoms of chronic heart failure due to systolic dysfunction. Patient enrollment has been completed and 250 patients have been randomized in this trial. The Company expects to report results in April 2015. About Breakthrough Therapy Designation The breakthrough therapy designation was enacted as part of the FDA Safety and Innovation Act of 2012 (FDASIA). The breakthrough therapy program is intended to streamline drug development and review of innovative new medicines that address certain unmet medical needs for serious or life-threatening diseases or conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence indicating that the drug may demonstrate a substantial improvement over existing therapies on at least one clinically significant endpoint. A breakthrough therapy designation conveys all of the fast track program features, as well as a commitment that FDA will work closely with the drug sponsor on an efficient drug development program. The statute calls for reducing exposure of patients to a potentially less-effective active control drug. However, FDA intends to expedite the development and review of a breakthrough therapy by intensively involving senior managers and experienced review staff in a proactive, collaborative, cross-disciplinary review. About Heart Failure Heart failure is the inability of the heart to pump blood efficiently due to weakening and enlargement of the ventricles. Nearly 6 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 Sates, 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. About MYDICAR MYDICAR uses gene therapy to selectively target and restore SERCA2a enzyme levels by transferring the SERCA2a gene directly into cardiac muscle cells, which improves 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 the 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 CUPID 1, 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 CUPID 1 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.