Pharma finds creative new ways to be reprehensible

The pharmaceutical industry is in the business of making profits. It’s not in the business of improving the health of individuals or populations, nor does it care about the cost of health care, even as those costs spiral out of control in the US.

This is hardly news, I know. The behavior of pharma, along with its reputation, has perhaps sunk lower than that of the tobacco industry. Public disapproval and huge monetary fines for illegal activities have no impact. In its quest for profits, pharma finds creative new ways to sink to ever greater depths.

An article in a recent issue of The New England Journal of Medicine illustrates this.

Thwart the development of generics: Plan one

The article, ‘Using a Drug-Safety Tool to Prevent Competition,’ discusses strategies (undoubtedly hatched in a high-powered legal department) to prevent generic drugs from coming to market. Drugs that have a potentially high risk of harm can be approved by the FDA and prescribed to patients if the manufacturer puts in place a Risk Evaluation and Mitigation Strategy (REMS). The intention of the congressional legislation that made this possible was to allow important new drugs to reach patients. Without it, drugs that appeared to pose safety issues could not be approved. The idea behind REMS strategies is that, by taking great care, these risky drugs can be used in such a way that the benefits outweigh the risks.

Brand-name drug manufacturers have taken advantage of the REMS legislation in two ways, both designed to prevent the release of generic equivalents.

First: In order to sell a generic drug, the manufacturer must prove that its product is “bioequivalent” to the branded version. To conduct such tests, the generic manufacturer must have access to samples of the brand drug. One way to avoid revealing the ingredients of a patented drug is to claim that doing so would violate the manufacturer’s REMS program. The Swiss-based drug company Actelion initiated lawsuits against two generic manufacturers seeking to make a generic equivalent of its drug bosentan (Tracleer). Actelion claimed the generic companies did not satisfy the requirements of its REMS program. (The suit was recently settled, but the terms of the agreement remain undisclosed.)

Thwart the development of generics: Plan two

Second: Some high-risk drugs are no longer protected by a patent on the brand-name original (an example is thalidomide, which is used to treat leprosy). This means the active ingredients are no longer a secret. To prevent the creation of generic equivalents in this case, a second strategy was devised: patenting the REMS program itself. Celgene (the manufacturer of thalidomide) sued Barr Laboratories (which wanted to market a generic equivalent), claiming that Barr would be infringing on Celgene’s patented REMS program. Barr could have come up with its own REMS program, but Celgene took the legal battle one step further.

Celgene also filed a citizen’s petition demanding that the FDA refuse to approve any generic thalidomide, because any non–patent-infringing REMS would pose “unacceptable risks” by “compound[ing] the confusion and burdens associated with thalidomide risk management and mak[ing] it more likely that the system would be compromised.”

Barr backed down and abandoned its plans. One more victory for big pharma. One less opportunity to treat leprosy at an affordable cost.

The lack of generic equivalents hurts individual patients — financially, of course, but it’s also the case that patients are less likely to maintain a treatment plan that requires filling expensive prescriptions. It also hurts the population at large. A health insurance policy may subsidize the cost of brand-name drugs, thereby helping individual policy holders. But the exorbitant cost of such drugs will be passed on to all of us in the form of higher premiums.

Orphan diseases and profit-driven medicine

Just a footnote. When I looked up Actelion in Wikipedia (the company that used its REMS policy to keep its ingredients secret), I couldn’t help but think the entry had been written by someone from the company’s PR department:

Actelion specializes in orphan diseases. Often R&D investments in such diseases are low because companies see no ROI. Obviously, this is a serious problem for patients affected by a rare disease. Orphan diseases often affect very vulnerable patient groups such as children; Actelion keeps investing in such areas.

As it happens, another article in the same issue of NEJM (‘The Calculus of Cures‘) gives a different perspective.

More than half the drugs approved by the FDA since 2009 have been for orphan diseases and high-risk cancers. Why? Because it’s much less expensive to develop these drugs than to develop drugs that treat more prevalent conditions, such as high blood pressure, elevated cholesterol, or diabetes. The cost of a trial is $25,000 per patient, which can amount to 40% of expenditures (in phase 3 trials). Clinical trials for orphan diseases can be much smaller than those for diseases that affect the population at large.

It’s also much less expensive to “sell” (i.e., market) orphan drugs. They are prescribed by specialists (such as oncologists) and purchased by hospitals. This market is much easier to target than primary care physicians, who must be wined, dined, educated in exotic locales, and visited frequently by expensive sales reps. Plus, in the US, there’s all that expensive direct-to-consumer advertising. It would make no sense to saturate TV and magazines with ads for a drug that treats an orphan disease.

My heart goes out to those who suffer from orphan diseases, as well as to their families. It’s fortunate that the economics are such that pharma takes an interest in at least a few of these rare (usually genetic) disorders. The flip side, however, is that when the science of medicine is driven by profit, pharmaceutical research neglects the leading causes of death (partly because it doesn’t want to compete with the generic drugs already available). This is an unfortunate side-effect of profit-driven medicine.

Sometimes I have to wonder: Isn’t there a fundamental and troubling conflict of interest between profit-driven medicine and population health?

Image: Canadian Foundation for Healthcare Improvement

References:

Ameet Sarpatwari, Jerry Avorn and Aaron S. Kesselheim, Using a Drug-Safety Tool to Prevent Competition, The New England Journal of Medicine, April 17, 2014, Vol 370 No 16, pp 1476 – 1478

Robert Kocher and Bryan Roberts, The Calculus of Cures, The New England Journal of Medicine, April 17, 2014, Vol 370 No 16, pp 1473 – 1475