Multaq (Sanofi's dronedarone) has had a turbulent time on the market since its launch in the United States in 2009. Given the high unmet need for safe and effective new drugs to maintain a normal sinus rhythm in AF patients, analysts had predicted peak year annual sales of up to $4 million for Multaq. However, a number of factors have restricted Multaq's uptake thus far and will continue to limit its future commercial prospects.
Firstly, the key efficacy end point used in Multaq's pivotal AF trial (the ATHENA study) was unconventional for this indication and we believe that the drug's data failed to fully resonate with prescribers. This effect was compounded by Multaq's modest efficacy on traditional antiarrhythmic measures, which interviewed thought leaders tell us is one of its key drawbacks. These issues aside, safety has been the watchword for Multaq in 2011 and we predict that one event in particular will have a major impact on the drug's future outlook. While January witnessed a liver safety alert being issued by regulatory agencies, July saw the suspension of Multaq's Phase III PALLAS trial in permanent AF patients; what was once seen as a strategic move to expand the drug's share of the AF market, ended with alarming results Multaq was shown to significantly increase the risk of mortality in patients with permanent AF compared to placebo. We expect that this event will be hard to overcome for Multaq despite the fact that very different patients were studied in the PALLAS trial compared to the drug's earlier, successful, ATHENA study.
As the medical community begins to re-evaluate Multaq's value proposition, what emerging therapies are in development for AF, and do they have the potential to address the remaining unmet need for safer and more effective antiarrhythmic drugs. In the sections below, I profile two key therapies that are in early stage development for AF.
- Oral vernakalant (Cardiome/Merck). The IV formulation of this new antiarrhythmic won approval in Europe last year (where it is marketed as Brinavess) for the acute cardioversion of AF. Oral vernakalant, on the other hand, remains in early clinical development. Cardiome had previously completed Phase II testing of oral vernakalant; however, Merck has since decided to study the drug in a new series of Phase I and II trials using higher doses. Although amiodarone's high level of antiarrhythmic efficacy creates an important barrier to entry for emerging antiarrhythmic drugs for AF, we believe that oral vernakalant has the potential offer important benefits over existing treatment options.
- Vanoxerine (ChanRx). Vanoxerine was initially in clinical development for Parkinson's disease and depression but recent preclinical studies have revealed its prominent antiarrhythmic effects. ChanRx, a startup company that was spun out from a CRO specializing in cardiac safety studies, recently announced that it had closed its Series A funding to advance IV vanoxerine through to Phase IIb development for AF cardioversion.
Oral vanoxerine remains in preclinical development, but a recent study provided the first insight into its efficacy for AF; the drug terminated AF and atrial flutter in a disease model of AF and prevented the arrhythmias from being re-induced.
In the antiarrhythmic drug arena, 2011 has been a year of re-evaluation, by physicians and regulators, of Multaq's risk-benefit profile. Nonetheless, the diverse AF pipeline holds great potential. In addition to oral vernakalant and vanoxerine, several other companies are developing novel agents for AF that we anticipate will provide important benefits to patients and propel growth of the AF market. In particular, atrial-specific antiarrhythmic drugs, that are in early stage clinical development by Xention and Bristol-Myers Squibb/Teijin, could have an unprecedented level of safety and, therefore, satisfy a major unmet need in AF.