Dr. Peter Bach is the Director of the Center for Health Policy and Outcomes at Memorial Sloan-Kettering Cancer Center and, as such, is often on the front lines of the public debate on health care. His particular focus is on drug costs and the value that new medicines may (or may not) bring to society. Whether you agree with him or not, Dr. Bach’s ideas are always worthy of attention.
At the inaugural STAT Health Care Summit, Dr. Bach was again provocative, in this case questioning the growing investment being made in finding treatments for rare diseases. The latter are defined as impacting less than 200,000 people in the U.S Dr. Bach believes that we over committing in investing in rare disease R&D. Rather, he points out that the number one killer of Americans is still cardiovascular disease (CVD). Would society be better off if more R&D were to be focused on that, or other diseases that more broadly impact Americans?
Interestingly, Alex Harding of Atlas Ventures has jumped on this same topic. In a piece in The Timmerman Report entitled “We’ve Been Neglecting Common Diseases. We Need to Reverse This Trend.” Harding also feels that too much emphasis has been placed on finding treatments for rare diseases. He argues that one of the best ways for the biopharmaceutical industry to improve its reputation is “by developing treatments for the diseases that harm the most people.” He cites heart failure, chronic obstructive pulmonary disease, drug addiction and bacterial infections as areas that need a renewed emphasis.
Both make compelling arguments. But, if I was running an R&D organization, I would not invest in cardiovascular disease (CVD) at the expense of rare diseases.
Yes, CVD is the number one killer of Americans. However, we have numerous drugs to treat CVD: lipid lowering drugs, anti-hypertensives, thrombolytics, etc. Furthermore, there are multiple mechanistically different drugs in each of these categories which can be used alone or in combination to help maximize treatment. In addition, many of these drugs have been used for years and are now generic – which to payers means “cheap”. Thus, if someone wanted to embark on an approach for a novel CVD drug they would have to be able to prove that their new drug would be at least as safe as existing therapies (to satisfy the FDA) and, just as important, be shown to be superior to all current treatments in order to convince payers to allow patients access to such a new drug. A clinical program to deliver on these requirements in general takes at least a dozen years and 1 -2 billion dollars. This type of investment is not routinely made even by the biggest companies.
These costs are not an exaggeration. Harding cites the PCSK9 blockers as a success story in the CVD field. These drugs which, in combination with statins, can lower LDL-cholesterol (LDL-c) to less than 50 mg/dL – an incredible breakthrough. But the value of these drugs had to be proven with multiyear, very expensive CV outcomes studies with more than 20,000 patients – studies that demonstrated that reducing LDL-c to these levels actually resulted in fewer heart attacks and strokes. These data finally convinced payers of the value of the PCSK9 inhibitors and they began allowing heart patients access to them. But now the bar is set extremely high. Anyone coming forward with a new lipid modulating drug will have to prove its superiority to PCSK9/statin combinations – a daunting hurdle.
Given this situation, it’s no surprise that major pharmaceutical companies like Pfizer and Sanofi, have abandoned CVD R&D. Furthermore, many big pharma companies have entered the rare disease space. The rationale is simple. Rare disease R&D programs require small clinical trials involving hundreds of patients (as opposed to thousands in CVD) to gain regulatory approval. Also, favorable pricing can be obtained for rare disease drugs as they treat diseases that are not only very costly to society but also are often fatal. Finally, sales of these drugs require small sales forces thereby reducing expenses. These factors make the rare disease space very attractive.
This is not to say that biopharmaceutical companies are focused exclusively on rare disease R&D. Major efforts are ongoing across the board in cancer (which can be considered as a collection of rare diseases), vaccines, immunological disorders, diabetes, arthritis, etc. But, in therapeutic areas that are already reasonably well served, the hurdles are high enough to discourage further work.
So, what about CVD, the nation’s leading killer? To be frank, the main driver of this disease is obesity and this epidemic is growing. A recent article in The New England Journal of Medicine predicted that by 2030 nearly 50% of U.S. adults will have obesity and the prevalence will be higher than 50% in 29 states and not below 35% in any state. In addition, by 2030 nearly 25% of American will be severely obese. This will drive increases in CVD, as well as diabetes and certain types of cancer in the coming years. If we really wanted to impact CVD, more investment is needed in reducing the incidence of obesity rather than new CVD drugs.
It’s important to recognize that an R&D organization must use its resources to maximize the return on a company’s investment- which in big pharma is on the order of $7 – 10 billion per year. To do that, investments must be made in therapeutic areas where the odds of technical, regulatory and commercial success are high. Unfortunately, CVD is not such an area.
Powered by WPeMatico