Celladon Corp, a biopharmaceutical company focused on the discovery and development of innovative treatments for cardiovascular diseases, announced that six-month data from its phase-2 clinical trial of Mydicar show improvements in clinical outcomes and disease markers in advanced heart failure patients treated with the genetically targeted enzyme replacement therapy.
The study met its primary safety and efficacy endpoints for high dose Mydicar versus placebo. The primary efficacy endpoint is a composite endpoint that encompasses the simultaneous assessment of patients’ clinical outcomes, exercise tolerance, heart failure symptoms, biomarkers, and cardiac function. Barry Greenberg, professor of Medicine at the University of California, San Diego, presented the data in advanced heart failure patients as a late-breaking trial presentation at Heart Failure Congress 2010, the annual meeting of the Heart Failure Association of the European Society of Cardiology.
“Cardiologists have limited treatment options available for patients with advanced heart failure,” said Dr Greenberg. “Our data show that patients who received Mydicar showed evidence of clinical improvement and had less worsening of heart failure and cardiovascular events requiring hospitalizations. What was most impressive to me was that the effects of Mydicar were consistent across a wide range of domains and clinical endpoints that are commonly used to assess the status of heart failure patients. I am very encouraged by these results and optimistic that larger studies will confirm these data. Confirmation of these findings in larger trials would provide us with a much needed new approach for treating patients with advanced heart failure.”
High dose Mydicar treated patients had a statistically significant reduction in cardiovascular events as defined by death, the need for left ventricular assist device (LVAD) or cardiac transplant, worsening of heart failure or heart failure related hospitalizations, which translated into a of 50 percent risk-reduction in favour of high dose Mydicar (hazard ratio 50 per cent versus placebo; P=0.040). In addition, the mean duration of hospitalization in the Mydicar high dose group during the six-month period was 0.2 days/patient, a substantially shorter period of time than the 2.1 days/patient of the placebo treated group.
Additionally, patients treated with high dose Mydicar improved significantly in their heart failure symptoms, their exercise tolerance, serum biomarkers and cardiac function. Specifically, the quality of life worsened by +3.4 points for placebo treated patients but improved by -10.3 points for Mydicar treated patients, as measured by the Minnesota Living with Heart Failure Questionnaire; exercise tolerance, measured with the six-minute walk test, decreased (worsened) in the placebo group by 87 meters but increased by one meter in the Mydicar group. A serum biomarker of heart failure, NT-ProBNP, worsened by +5540 pg/mL in placebo treated patients, and improved by -13.5 pg/mL in Mydicar treated patients, cardiac function worsened (heart further enlarged) by 18.2 mL (left ventricular end-systolic volume) in the placebo group, but improved by -9.6 mL in the Mydicar group, indicating a reverse remodelling of the damaged heart in the Mydicar treated patients.
Krisztina Zsebo, president and CEO of Celladon, said, “The consistency of these improvements across multiple outcomes measures is very encouraging. The positive results of the study suggest that MYDICAR® might have a significant impact on the progression of advanced heart failure, either slowing it down or possibly reversing the course of the disease, which is tremendous progress for more than 350,000 advanced heart failure patients in the United States that are estimated to fall under the CUPID population.”
Mydicar is a genetically targeted enzyme replacement therapy intended to restore levels of SERCA2a, a regulator of calcium cycling and contractility.