France’s Servier has been granted approval in Europe for Procoralan (ivabradine), the first in a new class of drugs for the treatment of angina pectoris.
Procoralan is the first pure heart rate–lowering agent and acts by selective inhibition of the cardiac pacemaker If current that controls the spontaneous diastolic depolarisation in the sinus node and regulates heart rate. Procoralan’s effects are selective to the sinus node and the new agent has no effect on intracardiac conduction, myocardial contractility or ventricular repolarization.
Unlike beta blockers, the most common current treatment for angina, Procoralan is free from sexual disturbances, respiratory side effects caused by constriction or spasm of the airways, bradycardia or rebound phenomena, claims Servier.
The new product has been cleared by the European Medicines Agency for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who have a contraindication or intolerance to beta-blockers.
Approval was based on the results of a 5,000-patient clinical trials programme that has compared Procoralan to placebo, the beta-blocker atenolol and calcium channel blocker amlodipine. In these trials, Servier’s drug was associated with a significant decrease in angina attacks, and the twice-daily dosage regimen provided uniform efficacy over 24 hours. A sustained reduction in heart rate was demonstrated in patients treated for at least one year and no rebound effect occurred following the withdrawal of treatment.
Heart rate reduction is one of the main therapeutic goals in angina treatment. However, existing treatments do not exclusively reduce heart rate and their use is often associated with unwanted pharmacological actions and poor tolerability. Moreover, stable angina patients very often have a high heart rate.
Servier has also started additional trials of Procoralan outside the stable angina arena, including a morbidity/mortality trial - BEAUTIFUL - that will include more than 10,000 coronary patients with left ventricular dysfunction. Trials in other indications such as heart failure or acute coronary syndrome are also on the cards.