Date: 2014-08-11
Type of information: Treatment of the first patient
phase:
Announcement: treatment of the first patient
Company: Celladon (USA - CA) Imperial College London (UK) British Heart Foundation (UK)
Product: Mydicar®
Action
mechanism: gene therapy/ enzyme replacement therapy. Mydicar® is a genetically-targeted enzyme replacement therapy for advanced heart failure. It 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 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®.
Disease: heart failure
Therapeutic area: Cardiovascular diseases
Country: UK
Trial
details: The 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),\" 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.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.
Latest
news: * On August 11,2014, the Imperial College London announced the start of a new clinical trial that will assess gene therapy for patients with heart pumps and provide detailed insight on its impact on the heart muscle. A patient with a mechanical heart pump has received a new gene therapy for heart failure at Harefield Hospital, London. Heart failure occurs when the heart no longer pumps blood effectively and it affects hundreds of thousands of people in the UK. Some individuals with an advanced heart failure can be fitted with a Left Ventricular Assist Device (LVAD), which supports the failing heart and aims to restore normal blood flow. The LVAD is an electrically driven pump, moving the blood from the left ventricle into the main artery (aorta) so it can circulate the oxygen-rich blood to the rest of the body. Individuals with advanced heart failure who require a transplant may be fitted with an LVAD to keep them alive until a suitable donor heart becomes available. Currently there are around 100 to 150 people in the UK living with an LVAD. The new trial, led by Imperial College London and funded by the British Heart Foundation (BHF) and Celladon Corporation, will explore whether this gene therapy could help these patients’ hearts recover and potentially provide an alternative treatment. It is the first study of gene therapy in this patient group. This particular gene therapy is designed to increase levels of SERCA2a protein in heart muscle cells. SERCA2a plays an important role in heart muscle contraction. Genes are inserted into the heart muscle cells to increase the level of SERCA2a using a harmless engineered virus that is based on a naturally occurring virus. In this study the research team will take small biopsy samples of the heart muscle six months after treatment to measure if the gene is present, detectable and functional in the patients’ hearts. The research team plan to evaluate how this therapy works in 24 patients with advanced heart failure who are fitted with LVADs. Of the patients enrolled in the study, 16 will be treated with the gene therapy and eight will be treated with a placebo. The new study will be the first to evaluate whether gene therapy is delivered to the heart muscle and if its effectiveness is compromised in patients with antibodies to the virus, which delivers the gene.Previously patients with an antibody to the naturally occurring version of the virus (about 50-60 per cent) have been excluded from a larger ongoing CUPID2 trial, which is investigating the benefits of gene therapy in people with heart failure but no LVAD device. Patients were excluded because it was believed possessing the antibody would render the virus less effective at inserting the gene into the heart muscle. However the actual effect of the antibody has never been explored in patients. This new study will evaluate the effectiveness of the gene therapy in both those patients who have the antibody and those patients without the antibody in order to make a comparison. This trial complements the larger ongoing CUPID2 trial, also funded by Celladon Corporation, which is investigating the benefits of gene therapy in 250 people with less advanced heart failure from Europe and the USA, including 14 patients from the UK. 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 FDA for this program and expects to report results from this clinical trial in April 2015.
