Antiarrhythmics: RSD1235 woes reduce market potential but not clinical impact

Arrhythmia is defined as an irregular heart rhythm, or an abnormality in the timing or pattern of the heartbeat, causing the heart to beat too rapidly, too slowly, or irregularly. Due to the complex nature of the condition, comprehensive epidemiology data on the prevalence of arrhythmia as a whole is difficult to come by. However, accurate data does exist for AF, the most common form of arrhythmia; it suggests a prevalence of chronic AF in the seven major markets of 8.5 million in 2005, which will rise to over 10 million by 2015.

Moreover, patients with AF are at high risk of suffering from a stroke, with over 40% of patients in the taking warfarin to prevent strokes. As such, safe and effective treatment of AF is critical for this patient group.

Despite the importance of safe and effective treatment for AF patients, the market for antiarrhythmic drugs is relatively small, with sales having only grown by 1.8% between 2004 and 2005 to just over $1 billion, according to IMS Health. What this means is that there has historically been a lack of innovation in antiarrhythmic R&D, with no new products having been introduced to the market since the last decade. 

The antiarrhythmics market across the seven major markets has experienced a sharp decline in sales over recent years, primarily due to the loss of patent protection for Sanofi-Aventis' Cordarone (amiodarone) in the US in 2002, and generic erosion therein. However, moving forward it appears that the antiarrhythmics market is on the brink of rapid expansion due to the expected launch of five novel products between 2007 and 2010, and a billion dollar market looks set to triple in size by 2015.

Small pipeline, huge potential, but...

One would think that being such a small market, drug developers would not view the antiarrhythmics market as a worthy investment for R&D dollars. The reality, however, is that the antiarrhythmics market is attracting significant interest from both big pharma and small, specialty pharma alike, as they each attempt to develop the next gold-standard treatment for cardiac arrhythmia, particularly AF.

A recent analysis of R&D activity within the antiarrhythmics market by Datamonitor has identified 13 projects currently undergoing clinical trials for the treatment of cardiac arrhythmia, two of which are currently in registration. Of these projects, three seem to have sufficient potential to drive sales of antiarrhythmics and triple the size of the market between 2005 and 2015. Cardiome's RSD1235 (intravenous), Sanofi-Aventis' follow-on to Cordarone, Multaq (dronedarone), and P&G Pharma's Stedicor (azimilide) each have significant patient potential.

All three are expected to generate sales of greater than $500 million and command over 60% of the entire antiarrhythmics market by 2015. Why? The key reason is that each product improves patient safety, and ultimately if a drug is safer compared to other products, physicians will go for these despite the expected premium price compared to generics.

... RSD1235 setbacks impact market forecast

In May, when Datamonitor's analysis of the antiarrhythmics market was published, much excitement surrounded Cardiome's RSD1235 (intravenous), with Datamonitor forecasting that, by 2012, RSD1235 would become a blockbuster and ultimately command over 25% of the entire antiarrhythmics market by the end of 2015.

However, on May 30, an "administrative, rather than scientific" issue with RSD1235's new drug application (NDA) filing prompted the FDA to release a refusal to file (RTF) letter for RSD1235. Cardiome, along with development partner Astellas Pharmaceuticals US, is now aiming for a Q3-Q4 2006 re-submission of the drug's NDA, delaying approval until at least Q4 2007.

The critical element of the RTF, confirmed by Cardiome officials, was that no additional clinical data had been requested, rather requests for "accurate and consistent data with no omissions." In essence, the data was good, but the filing's presentation and format were not. Therefore, RSD1235 is still believed to have significant potential in the pharmacological treatment of AF, as there is a considerable unmet need for safe and effective treatments.

However, blockbuster sales for the drug would now appear to be unlikely as a full year of potential sales for RSD1235 have now been lost. This is a highly embarrassing milestone in the history of Cardiome, and serves as a reminder to all pharmaceuticals companies, large and small, that approval is not guaranteed regardless of how much excitement surrounds a product.

Re-forecasting the market, P&G Pharma's Stedicor (azimilide) now looks likely to be the highest selling pipeline antiarrhythmic by 2015, with RSD1235 having to settle for second-place.

Related research:

§          Pipeline Insight: Antiarrhythmics - RSD1235 in a class of its own priced $11,400

§          Sanofi-Aventis: PharmaVitae Profile 2005 priced $5,700

§          Stakeholder Insight: Heart Failure - Pumping Up Therapy Will Prevent Failure priced $15,200