June 16th, 2014

European Medicines Agency Initiates Review of Ivabradine

There may be trouble on the horizon for ivabradine, a heart drug marketed by Servier under the brand names of Corlentor and Procoralan. The drug is widely available in Europe and elsewhere, though it is not available in the U.S., where it is under development by Amgen. Although it hasn’t been widely reported,  the European Medicines Agency said last month that it has started a review of the drug based on troubling findings from the SIGNIFY study. (Ivabradine is used to treat patients with long-term stable angina and long-term heart failure.)

The main results of SIGNIFY are scheduled to be presented on August 31 at the European Society of Cardiology meeting in Barcelona. However, on May 8, the European Medicines Agency announced that it had initiated a review of ivabradine based on preliminary results:

The review follows preliminary results from the SIGNIFY study, which was evaluating whether treatment with Corlentor/Procoralan in patients with coronary heart disease reduces the rate of cardiovascular events (such as heart attack) when compared with placebo (a dummy treatment). Patients in the study received up to 10 mg twice daily, which is higher than the currently authorised maximum daily dose (7.5 mg twice daily), and the results showed a small but significant increase in the combined risk of cardiovascular death or non-fatal heart attack with the medicine in a subgroup of patients who had symptomatic angina (Canadian Cardiovascular Society class II – IV).

The European Medicines Agency will now evaluate the impact of the data from the SIGNIFY study on the balance of benefits and risks of Corlentor/Procoralan and issue an opinion on whether the marketing authorisation should be maintained, varied, suspended or withdrawn across the EU.”

Ivabradine slows the rate of the heart by inhibiting the so-called “funny” current within the heart’s natural pacemaker, the sinoatrial node.

It should be noted that Amgen recently announced that the FDA had granted fast track status to the drug. But it should also be noted that every FDA expert with whom I’ve spoken has said that the fast track designation means absolutely nothing (though in my experience it’s nearly always a good excuse for a company to issue a press release). In a statement Amgen said that it planned to submit the FDA filing for ivabradine for patients with chronic heart failure. The SIGNIFY trial included patients with chronic stable coronary artery disease without heart failure.

One Response to “European Medicines Agency Initiates Review of Ivabradine”

  1. Bassem Fouad, MD says:

    I think SIGNIFY should be revised with the 7.5mg bid to clarify is it dose or drug effect.