October 4, 2012 — This year’s European Society of Cardiology (ESC) Congress in Munich, Germany, was a stark example of exactly where the cardiovascular market space is headed. This congress fully emphasized the new and innovative technologies that are coming out on the medical device and medical technology side, while leaving the market’s pharmaceutical wing in the dust. In fact, out of the nine hours over three days and 18 seminars on cardiac therapy innovation, only one seminar, given by Amgen, spoke about a pharmaceutical interventional treatment for heart disease. Thus, if there is one message to take away from the ESC 2012 congress, it is that the pharmaceutical industry has moved away from the cardiovascular market
Prominent talks at the Congress included "Multimodality Image Fusion Technology for Enhancing Complex Transcatheter Cardiac Procedures" that was put on by Philips Healthcare, "Cardiac Contractility Modulation: An innovative device therapy for Heart Failure with narrow QRS" presented by Impulse Dynamics Germany and "Automated quantitative CTA software for systematic analyses of coronary artery disease" organized by Medis Imaging Systems. All in all, these seminars followed the industry trend of shifting cardiac focus toward devices — in particular less-invasive procedures such as transcatheterization — and toward new software solutions that will help physicians with diagnosis. However, biotech giant Amgen did give a presentation called "PCSK9, a potential exciting new target for the treatment of high cholesterol," where they outlined the potential for using the PCSK9 enzyme that regulates LDL in humans as a target for the next generation of cholesterol-lowering therapies.
While the future of the cardiac space is in question, there are still some innovative new products hitting the market that can help patients and fill niche markets. One particularly interesting product that has already been approved in Europe is apixaban. The drug is an oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke and systemic embolism.
Recent secondary analysis derived from the results of the ARISTOTLE trials, published in September 2011, was discussed at the 2012 ESC Congress. The topic for discussion was that apixaban, of which 25 percent is excreted by the kidneys, did not present a risk of renal impairment for patients with atrial fibrillation.
The ARISTOTLE trial was conducted to compare apixaban to warfarin in patients with atrial fibrillation. The results of the trial showed that apixaban reduced the risk of stroke and systemic embolism by 21 percent mortality by 11 percent, and major bleeding by 31 percent relative to warfarin in patients with atrial fibrillation and one additional risk factor. Currently, apixaban is available in Europe under the trade name Eliquis, but approval was delayed by the U.S. Food and Drug Administration (FDA) in June of 2012.
The ARISTOTLE trial used three different avenues to look at glomerular filtration rate (GFR). The first two methods, the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EDI) equations, measure serum levels of creatinine. The third metric was cystatin C measurement. The secondary study looked at 14,884 patients and found that apixaban reduced major bleeding in patients with all levels of renal impairment. However, it also showed the greatest benefit for patients who had the most impaired kidneys (i.e., patients with eGFR < 50 ml/min), a population that cannot take warfarin or other oral anticoagulation due to fears of severe bleeding.
This study gives hope to this underserved population. Patients with impaired renal function are at the highest risk of stroke, yet are unable to receive the benefits of anticoagulants. Adding apixaban to their treatment regimen will reduce their risk of a major thrombotic event without the concomitant kidney effect. Assuming that the FDA eventually approves Eliquis for the sale in the United States, GSK and Pfizer will have a potential blockbuster in apixaban. However, even if the FDA continues to balk on approval of Eliquis, GSK and Pfizer may be able to gain approval for the highly renal impaired atrial fibrillation patient segment.
For GSK and Pfizer, the co-promotional partners selling Eliquis, there is an opportunity to enter a market that has previously been inaccessible. The study’s conductor, Dr. Stefan Hohnloser, did receive consulting fees and research grants from Pfizer and BMS. Thus, it is clear from their actions that the companies are trying to make a push for approval in the United States by funding these follow-up studies after the FDA issued a Complete Response Letter (CRL) requesting additional information on data management and verification. The approval of apixaban in the United States could also lead to off-label usage, with physicians knowing its efficacy profile versus warfarin. Thus, while pharma is moving away from cardiovascular therapies, there is still some hope for pharmaceutical advances in niche markets such as atrial fibrillation patients who have, or are at risk of, renal failure. The identification and development of these cardiovascular treatments appears to be the future of the industry for the foreseeable future.
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July 10, 2024 
