The strategy for cardiovascular disease prevention is currently changing in a big, expensive way. Many cardiologists are hopeful that PCSK9 inhibitors will soon bring an end to high cholesterol, effectively changing cardiology forever. Unfortunately, the pharmaceutical companies that developed these potentially miraculous drugs have priced them at a whopping $14-15K a year, more than fifty times the price of statins, the current standard of care. This high price point will lead to the highest therapy cost the United States has ever seen — a cost that will affect all Americans, especially lower income individuals.
Cardiovascular disease is the number one killer of Americans, causing around 610,000- or roughly one in every four- deaths each year. One of the best indicators available for cardiovascular health is low density lipoprotein cholesterol (LDL-C), or “the bad cholesterol”, levels. If you can get that magical number down below 70-130 milligrams per deciliter (mg/dL) depending on your risk category, then you are considered to have a low risk for cholesterol buildup in your blood vessels and a reduced risk of heart disease.
For some people, reaching that number simply requires switching to a “Mediterranean diet” and getting more exercise. However, for many people it requires medication. Currently, statins are the drug category of choice for lowering LDL-C levels.
Unfortunately, statins simply do not work for everyone, leaving a patient care gap of 25-40%.
While there are some steps that can be taken to aid these patients, such as stacking the non-statin therapy ezetimbe with a statin for additional LDL reduction, these combination therapies often still don’t get the job done. For a disease that causes 610,000 deaths a year, a patient care gap of 40% is, simply put, a big, scary deal.
The good news: PCSK9 inhibitors may be just the therapy to close that gap.
PCSK9 inhibitors are antibodies that can help regulate the body’s metabolism of LDL-C. They latch onto a protein called proprotein convertase subtilisin/kexin type 9, or PCSK9, which binds to the LDL-receptors, tagging them for destruction in the liver and keeping cholesterol levels high. By binding to PCSK9, the PCSK9 inhibitors allow the LDL receptors to continue binding to LDL, resulting in a lowering of cholesterol.
More good news: PCSK9 inhibitors are particularly good at lowering LDL-C in the patients who need it most — the ones who currently have no other options. Since the invention of these inhibitors, several trials have shown PCSK9 inhibitors decrease LDL-C in patients with familial hypercholesterolemia (FH), a genetic condition that leads to high cholesterol unmanaged by statins.
In light of these trials, the FDA approved the use of two PCSK9 inhibitors this past summer for use in patients with FH or clinical atherosclerotic cardiovascular disease (ASCVD). These patients have already had heart attacks or strokes due to plaque buildup in their arteries and do not benefit from statin therapy . It is estimated that 5-10M people have either FH or ASCVD. At roughly $15K annual cost per person for either PCSK9 inhibitor, the price to insurance companies and the people they represent- and charge- will be astronomical.
But that’s just the beginning. Many cardiologists, pharmaceutical companies, and insurance companies alike expect that those 5-10M people are just a small sliver of the population for whom these drugs will eventually be prescribed. If this is the case, it means that a huge number of people will potentially be prescribed PCSK9 inhibitors in the near future, at great expense. Estimates for the cost to the U.S. healthcare system of such an expansive prescription base for these expensive drugs are between $100-150B per year. PCSK9 inhibitors are by no means the most expensive per-use medications on the market, but at their current price point they are the most expensive drugs that require a lifetime of continued use.
Many people wonder why drugs like the PCSK9 inhibitors and other “biologics” are so expensive. Part of the answer is the high cost for a continued cycle of research and development for newer and better drugs. The making of the antibodies is expensive. Drug trials done properly are also expensive and require a wide range of participants to demonstrate broad spectrum efficacy. In fact, the drug companies do not make money unless their drug works well. In the end, it’s a balancing act between the economics of these high cost medications and the ethics of the inherent decreased access to care.
The United States government does not govern the price of drugs — the market does. In places like Europe or Canada, the costs of these drugs would never be set so high because they are set by the government. In fact, the European version of the FDA, the European Medicines Agency, rejected PCSK9 inhibitors until their prices were halved.
In America, specialty drugs like cancer drugs and those for Hep-C are inherently in low demand, which allows for a higher price only as long as the consumer, which is the insurance company in the United States, is willing to pay for it. If these conditions are met, that price point remains.
This high price point does provide some overall benefits. By consumers paying more here than in other countries for drug use, the United States foots the majority of the bill for the entire world when it comes to research and development of new drugs. Drugs like the PCSK9 inhibitors may be significantly more expensive in the United States than in Europe, but the revenue from prescription drug use in the United States has a global health impact. So the question becomes: is this a fair situation for Americans? Perhaps not — especially for those who cannot afford it. Yet, there is currently no other option if we support the continued development of novel medications.
The regulation of drug prices by the government has been in the national limelight lately, with people ranging from Martin Shkreli of Turing Pharmaceuticals, who raised the price of the AIDS-related drug Daraprim from $13.50 to $750 per pill overnight, to Bernie Sanders and Hillary Clinton who have been expressing a need for change on Twitter and in their campaign platforms.
Shkreli argues that his price increase for Daraprim was a consequence of this model: the economic necessity for research and development. In September, the BBC called Shkreli the “most hated man in America” and his face was all over the news. Hillary Clinton tweeted her outrage at him. Is there any difference between Shkreli’s 5000% price hike and the insanely high prices of such important drugs like the PCSK9 inhibitors?
The difference is in the need for R&D. Daraprim was developed over 40 years ago, unlike the brand new PCSK9 inhibitors, and is sufficient, unlike statins. Although Daraprim does treat a rare condition and has a low demand, the production cost to Turing Pharmaceuticals is very low, unlike the PCSK9 inhibitors.
So, what about PCSK9 inhibitors? Do the economic and ethical factors of such a novel and important pharmaceutical dictate and permit their extremely high ticket price? Only Amgen and Regeneron, the pharmaceutical companies selling them, seem to say yes. Pharmacies that stock the drugs, government agencies that study drug prices, and cardiologists are in agreement that the price point of the PCSK9 inhibitors is simply too high, even for a drug that so greatly reduces LDL-C, especially considering the possibility that they will be used by so many millions before the end of the decade.
People like Martin Shkreli give “Big Pharma” a worse reputation than it deserves, but he’s not the only culprit. When considering the price of drugs, the price of research and development and the demand must be considered. If the United States accepts the lion’s share of the responsibility for worldwide medication research and development, the costs to consumers in the United States may become untenable in this age of costly pharmaceuticals.
The introduction of PCSK9 inhibitors to the drug market could truthfully bring an end to high cholesterol and dramatically reduce cardiovascular disease across the world. However, Americans simply cannot bear the economic weight when the drugs cost each user nearly $15K annually for the rest of his or her life. The price must be reduced, but only time will tell by what means such a change will occur.
Brendan M. Everett, M.D., M.P.H., Robert J. Smith, M.D., and William R. Hiatt, M.D.
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