This year's line-up of Late-Breaking Clinical Trial sessions looks very interesting; with many trials having the potential to significantly impact clinical practice. The trial results will be presented over four days in separate sessions focusing on:
- Risk and benefit of dual antiplatelet therapy (DAPT),
- Anti-lipid therapy and prevention of coronary artery disease,
- Treatment of structural heart disease
- Drugs, devices and systems of care for ischemic heart disease.
Here, I have highlighted some of the late-breakers that I find the most interesting.
Topping the bill (in terms of interest level) is the reporting of results from the long-awaited IMPROVE-IT trial. The trial compares the efficacy of Merck's Vytorin (ezetimibe/simvastatin FDC) to simvastatin alone in reducing CV events in more than 18,000 ACS patients. The results of this trial, which began in 2005, are expected to have a significant impact on the future of the PCSK9 inhibitors as well as other future add-on antidyslipidemic agents.
Zetia (ezetimibe) was initially approved in 2002 to reduce LDL cholesterol; however, there were no studies testing its long-term effects on cardiovascular outcomes. Despite this, the drug has become the main add-on therapy for patients on statin therapy who have been unable to achieve their LDL-C goal. Since the release of the ENHANCE trial data in January 2008 the Zetia franchise has been exposed to sustained negative press which has resulted in a decline in U.S. sales, and the release of U.S. guidelines focusing on therapies with outcomes data (i.e., statins) will not have helped.
Therefore, the results of IMPROVE-IT are not only make-or-break for the Zetia franchise, but they are also expected to have much wider-reaching implications with regard to the LDL-C hypothesis (the lower the better), and the route to market for future treatments. If IMPROVE-IT meets its primary end point, then we believe that regulatory authorities will be far more inclined to approve therapies on the basis of their LDL-C lowering efficacy, allowing for a smooth approval for the PCSK9 inhibitors. Conversely, a negative trial result may delay the launch of the PCSK9 inhibitors (and other agents) until cardiovascular outcomes benefit is proven.
It is no coincidence that this trial will be presented just before the IMPROVE-IT study. ODYSSEY ALTERNATIVE compares Sanofi/Regeneron's alirocumab with Zetia in 314 patients with primary hypercholesterolemia and moderate, high, or very high cardiovascular risk, which are intolerant to statins. The final session of the clinical science special reports will also feature a run-through of all the results from the ODYSSEY clinical trial program. We expect a filing for alirocumab similar to that for Amgen's evolcumab before the end of 2014; however, Amgen's filing of a lawsuit in the U.S. District Court of Delaware claiming that alirocumab infringes several of the company's patents may put a spanner in the works.
Risk and benefit of DAPT
Current guidelines recommend 12 months of DAPT following an ACS event. However, results from recent trials (e.g., EXCELLENT and PRODIGY) have suggested that, following implantation of a stent, DAPT for 6 months was non-inferior to 12 months or 24 months therapy; but bleeding was increased with longer treatment duration. Thus, physicians are unsure regarding the optimal duration of DAPT. Data reported during the Late-Breaking Clinical Trial Session on Sunday November 16th (including results from ISAR-SAFE and the TAXUS Libert Post Approval Study [both of which have enrollments of approximately 4,000 patients], as well as DAPT study in over 20,000 patients) should shed more light on this issue.
Meet Members of the DRG Cardiovascular Team
Conor Walsh MSc PhD, Senior Director, and Graeme Green MSc, PhD, Principal Business Insights Analyst, from the DRG Cardiovascular, Metabolic, and Renal Disorders team will both be in attendance at the 2014 AHA Scientific Sessions. Should you wish to meet with them, please email us at: firstname.lastname@example.org