January 8, 2017

When Pfizer was in their laboratory doing research & development on their molecule, Sildenafil (Viagra), it was intended for pulmonary hypertension.  What Pfizer scientists discovered was that Sildenafil also caused erections.  Pfizer decided to shelve the idea of seeking an initial indication with the FDA for Pulmonary Hypertension since very few people suffer from it.  Pfizer instead invested a lot of money into creating a medical condition for which they could pursue an FDA indication: Erectile Dysfunction. It worked.

This isn’t the first time the pharmaceutical industry has created a medical illness. Pharma pursues these pathways so as to support bringing to market a drug that will be wildly successful by using marketing bravado for their newly minted illness.

Merck & Company was the first pharmaceutical company to bring Statins (cholesterol lowering drugs) to market. Although another pharmaceutical company, Sankyo, discovered the first Statin, they never brought it to market due to the adverse events.  Merck was intrigued and they pursued the pipeline.

Statins work by inhibiting cholesterol synthesis by the liver (Katzung & Trevor, 2015). Cholesterol is necessary for the synthesis of hormones like Estrogen and Testosterone.  Without cholesterol being synthesized naturally by the liver, offspring would not be born – children.  The mechanism of action of Statins is halting the liver from synthesizing cholesterol at a crucial step in the biochemical pathways HMG CoA. Statins are HMG CoA Inhibitors. When a person is diagnosed by a physician for having high cholesterol it is rarely the fault of the liver.  The incidence of genetic predisposition to elevated cholesterol is 1 in 500 (0.2% of the population) (Ned & Sijbrands, 2011).  It is known as Familial hypercholesterolemia.

“The altered gene (gene mutation) that causes familial hypercholesterolemia is located on chromosome number 19. It contains the information for a protein called LDL receptor that is responsible to clear up LDL from the blood stream. One in 500 individuals carries one altered gene causing familial hypercholesterolemia. These individuals are called heterozygotes. More rarely, a person inherits the gene mutation from both parents, making them genetically homozygous. Individuals who are homozygous have a much more severe form of hypercholesterolemia, with heart attack and death often occurring before age 30” (NHGRI -NIH, 2013)

If a person has Familial hypercholesterolemia they must start taking Statins by their early teenage years. Otherwise they will incur heart attacks and never reaching adulthood.  Thus elevated cholesterol in the Western World is rarely due to the liver or genetics and usually due to the individual’s dietary intake.  Undeterred, Merck set out to market a drug, Mevacor, that would lower cholesterol even if the liver was not the problem.  A blockbuster class of agents was born.

Merck ended up bringing to market 2 Statins, (Mevacor & Zocor), with the latter being more aggressive than the former in preventing the liver from synthesizing what it does naturally. Pfizer has the industry record for having the most successful drug ever brought to market. Not surprisingly it happens to be a Statin: Lipitor (atorvastatin). Lipitor was originally belonged to Parke-Davis Pharmaceuticals but Pfizer wanted it at all costs, initiating a hostile takeover of Parke-Davis, so as to take possession of Lipitor.  Pfizer in the end got Lipitor and laughed all the way to the bank.

The same goes for ED medications.

The reality is that Impotence or ED is largely caused by psychological problems (DSM-5). The American Psychiatric Association has impotence listed in their Diagnostic and Statistical Manual (DSM-5).

“Erectile problems that are situational and inconsistent and that have an acute onset after a stressful life event are most often due to psychological events. An age of less than 40 years is also suggestive of a psychological etiology to the difficulty” (American Psychiatric Association. (2013). Sexual dysfunctions. In Diagnostic and statistical manual of mental disorders: DSM-5, 5th ed., Washington, DC, p. 429).

The way to rule out whether impotence is due to vascular/physiological problems is determining whether the male ever has an erection.  If the male can have an erection at any time, morning, evening, sleep, etc., then their problem is not vascular nor physiologic but psychological (DSM 5).

Yet the marketing on behalf of the pharmaceutical industry to promote Cialis, Viagra, Levitra, etc. all hinge on the marketing message of “it could be a question of blood flow” (Viagra TV Commercial, 2014). The prevalence of the vascular etiology (“question of blood flow”) does not support the marketing claims of Pfizer.  So there is a disconnect between scientific fact and marketing goals. But pharma knew that if they brought to market such a class of agents it would be a huge blockbuster for the psychological etiology in spite of the fact that third party payers (private insurance companies) and the Centers for Medicare and Medicaid Services limited reimbursement of these drugs when they were first brought to market to  4 pills per month of Viagra (Medscape, 2002). Yet Pfizer knew their market: people would want the blue pill despite lack of medical reimbursement and despite not having a physiological “problem of blood flow” condition.

When Pfizer brought to market Viagra in the late 1990s, there was a huge outcry from advocacy groups decrying the reimbursement of such medications at the costs of US Taxpayers ( Klein & Sturm, 2002).  Those voices fell by the side due to the marketing muscle of pharma.  One could say their cries became impotent and pharma’s revenue reached climactic levels where all beneficiaries were very happy.

Marketing can be sheer genius and very profitable but especially in medicine.

 

References

American Psychiatric Association. (2013). Sexual dysfunctions. In Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed., p. 426). Washington, DC

Katzung, B. G., & Trevor, A. J. (2015). Agents Used in Dyslipidemia. In Basic & clinical pharmacology (13th ed., p. 609). New York, NY: McGraw-Hill Education.

Klein, R., & Sturm, H. (2002). Viagra: A success story for rationing? Retrieved from http://content.healthaffairs.org/content/21/6/177.full

Medscape. (2002). Viagra: A Success Story for Rationing? Retrieved from http://www.medscape.com/viewarticle/445003_2

National Human Genome Research Institute (NHGRI) – National Institutes of Health (NIH). (2013, December 26). Learning about familial hypercholesterolemia. Retrieved from http://www.genome.gov/25520184

Ned, R. M., & Sijbrands, E. J. G. (2011). Cascade screening for familial hypercholesterolemia (FH). PLoS Currents, 3, RRN1238. http://doi.org/10.1371/currents.RRN1238