New Drug Improves Rare Heart Disorder, But Could Tackle Common Heart Problems, Too

Long QT syndromes (LQTS) are a group of inherited disorders that make the heart particularly susceptible to arrhythmias – abnormal heartbeats that can lead to fainting, cardiac arrest or sudden cardiac death. Work by University of Rochester School of Medicine and Dentistry researchers has led to some of the most important discoveries surrounding the understanding and treatment of these disorders. At the Heart Rhythm Society annual meeting earlier this month, the team continued this progress, presenting data from a Phase 1 trial on a new drug that could lower the risk of arrhythmias in LQT3 patients.

LQT3 results from a genetic mutation in the heart’s sodium channels; the flow of sodium ions in and out of the heart helps it maintain a normal rhythm. The new drug, developed by Gilead Sciences, Inc. is the first to effectively target and correct the sodium channel abnormalities in LQT3 patients, who are not well protected with current treatment options, says lead study author Wojciech Zareba, M.D., Ph.D., director of Cardiology Clinical Research and the Heart Research Follow-up Program at the University. LQT3 patients usually receive therapies that treat the symptoms, but not the underlying mechanisms of the disease, including beta blockers, which are effective in some patients but not in others, and an implantable cardioverter defibrillator or ICD, which detects dangerous arrhythmias and shocks the heart back into a normal rhythm.

Spencer Z. Rosero, M.D., an associate professor of Cardiology whose work 20 years ago demonstrated the involvement of sodium channels in LQTS patients, worked closely with Zareba and led enrollment activities for the Phase 1 study.

With these positive results, Zareba is collaborating with Gilead in launching an international Phase 2 trial  which will involve 40 LQT3 patients recruited from centers in the United States, United Kingdom, Germany, Italy and the Netherlands. Patients will receive the experimental drug over a six month period and will be evaluated for prolonged reduction in QTc duration – a surrogate marker of arrhythmias in LQTS – and for the safety of the new drug.

Additionally, based on data that shows that disruptions in sodium channels play a role in other cardiovascular diseases, Gilead plans to start Phase 2 clinical trials with the involvement of Zareba and Rosero in patients with hypertrophic cardiomyopathy and ventricular tachycardia and ventricular fibrillation. Hypertrophic cardiomyopathy occurs when the heart muscle becomes thick and can’t pump blood throughout the body, leading to arrhythmias. Ventricular tachycardia and ventricular fibrillation are both abnormal heart rhythms that start in the ventricles and often occur following a heart attack.

Zareba, also a professor of Cardiology at the medical school, says that no new drugs to treat arrhythmias have been developed in the last 20 years. He believes this new drug could usher in a new era of successful development of much needed anti-arrhythmic therapies.