The most eagerly awaited study presented at last week’s American College of Cardiology meeting was Amgen’s FOURIER clinical trial. This study involved 27,564 patients with cardiovascular (CV) disease, 80% of whom had already experienced a heart attack. The goal was to show that Amgen’s drug, the PCSK9 inhibitor called Repatha, when added on top of statin therapy, further reduced CV events when compared to statin therapy alone. Could a PCSK9 inhibitor be a major breakthrough against the world’s leading killer? FOURIER was designed to find out.
There were high hopes for the FOURIER trial. Current dogma is that the more you can lower your LDL cholesterol (LDL-c), the lower the risk of a heart attack or stroke. Repatha did, in fact, produce unprecedented LDL-c lowering in FOURIER. Those patients taking optimal doses of statins had on average LDL-c levels of 92mg/dL, whereas those who were also dosed with Repatha had average LDL-c levels of 30mg/dL. The latter patients did have fewer CV events, but of a smaller magnitude than hoped. The PCSK9 had only a 15% decrease in CV events, only half of what had been hoped.
This lower-than-expected benefit has set off a debate among heart disease experts. Some experts, like Dr. Eugene Braunwald of Harvard Medical School, hailed these results: “This is like the era of statins coming in.” However, others are concerned over the costs of this drug. Repatha is expensive, with a list price of over $14,000 per year--although it is believed that payers have negotiated prices that are closer to $9,000/year. But even at the lower price, this is still a relatively expensive drug given the modest benefit it provides for the heart disease population. It will be interesting to watch how the negotiations between Amgen and insurers unfold over the coming months. The debate over who would be best served by this drug is only beginning.
However, Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, has a different concern about the FOURIER study and its results. She is concerned about bias. As she told the New York Times, Amgen paid for the study, helped design it, collected the data and helped write the paper. Dr. Redberg essentially believes that we shouldn’t accept the Amgen data at face value. Clearly, Amgen’s actions must be scrutinized.
Really?
Dr. Redberg’s unfortunate comments play into the fears of those who believe that any science generated by the biopharmaceutical industry cannot be trusted. Frankly, that’s absurd. What Dr. Redberg doesn’t mention is that Amgen did not design this trial in a vacuum; they did it in collaboration with expert cardiologists as well as the FDA. She doesn’t mention that the study was carried out by investigators at leading teaching hospitals. Yes, the data were collected by Amgen, but the data analyses were done independently by a team of academic researchers led by Dr. Marc Sabatine, chairman of the Thrombolysis and Myocardial Infarction Group at Brigham and Women’s Hospital. The integrity of these distinguished researchers shouldn’t be so easily dismissed by Dr. Redberg.
Yes, Amgen did pay for this study–I would guess about $500 million or so. FOURIER is a landmark study for the cardiovascular field. It shows that the benefits of LDL-c lowering may begin to level off at a certain point. The medical community as well as the FDA are grateful for these results as they add to our understanding of the role of LDL-c in CV disease. However, it must be pointed out that the costs of such a study are beyond the means of the NIH or any other publicly funded institution. Only the private sector has the funds needed to carry out such a large clinical trial. And before the “pharmascolds” begin their rants about conflicts of interest, one has to remember that a lot of these expensive, large clinical trials often result in failure. In late January, Pfizer had to stop the development of their own PCSK9 inhibitor, bococizumab, because their 32,000 patient SPIRE-1 and 2 studies showed that the effects of bococizumab faded over time. This is not unique to PCSK9 clinical trials. Large, long-term trials have failed with other CV drugs like the CETP inhibitors, and even for drugs in other fields, particularly with Alzheimer’s disease drugs.
Outcome studies such as these are among the riskiest in pharmaceutical R&D. They are, however, necessary to advance the field of medicine. Because of the risks, these studies are undertaken with great care and with the advice and oversight of many outside of the company that is footing the bill for the study. Foolish comments like those by Dr. Redberg are of little use as the industry works to advance medical science.
