Wednesday 20 December 2017


It's an ill wind that blows nobody any good. I cite the terrible story of Thalidomide in my Human Physiology course as an example of paying attention to epidemiological evidence and making connexions. After it was shown that this morning sickness drug could cause grievous damage to the child within, the drug was taken off the market. Almost as soon as it was withdrawn as a treatment for nausea, it was found to be singularly effective against Erythema nodosum leprosum ENL one of the more obvious effects of an infection by Mycobacterium leprae. There aren't as many people affected by leprosy (who can afford any sort of drugs) as pregnant women but Thalidomide has been earning its keep by damping down TNFα, a pro-inflammatory cytokine. If costs $1billion to bring a novel drug to market and, if you've invested enough money in development, there is a certain pressure to find some sort of therapeutic use even if not the one that first launched the project.

The most famous example of this is Sildenafil [structure L],which was being developed, in the late 1980s, by a team in Pfizer to combat hypertension. Theory and evidence had shown that the compound inhibited an enzyme  cGMP-specific phosphodiesterase type 5 PDE5 which broke down a chemical messenger called cGMP. This left more cGMP in circulation and it was known that this would cause peripheral vasodilation, at least in rats. Relaxing the smooth muscles of the arteries should help lower blood pressure. But when it came to human trials, no such effect could be convincingly demonstrated - damn those inconvenient statistics, the marketing people must have thought. After a couple of no significant difference trials, the money people called in the development team and gave them an ultimatum: the plug would be pulled and the costs written off if nothing convincing turns up. There was one trial still lurching along: a Phase I case-control clinical trial involving Welsh coal miners - then an endangered species after a decade of Thatcher economics. That also had shown no demonstrable effect on hypertension. But in the follow-up interviews, the researchers threw out a generic "anything else we should know about?" and one of the miners mentioned that he'd been experiencing some night-time stiffness. The other miners chirped up with a chorus of "Me toos" and Viagra was born, first as a concept and then as a product. It was patented by Pfizer in 1996, approved by the FDA two years later and has been making money hand-over fist for Pfizer ever since.
Several years afterwards, GlaxoSmith Kline and others launched a me-too drug called Vardenafil [structure L], which is also an effective inhibitor of PDE5. No surprises there because it's hard enough to find the chemical differences between the two compounds. If the whole drug market wasn't driven forward by money, we might have required GSK to look for other drugs rather than adding nothing to a problem that was already essentially solved.
Viagra has also been remarkably kind to the people of Ringaskiddy, Co Cork because that has been a major production facility for the drug since 1998. The wages and salaries from the Pfizer payroll have supported a rake of other businesses in the area: sandwich shops, petrol stations, hair-salons, convenience stores. We can dismiss as nonsense the story which gets rechurned whenever Viagra is in the news: there are no Sildenafil fumes wafting about in the air, and none was leaked into the water-supply. Any priapic effect is entirely down to the power of suggestion.  And yes, Viagra is in the news this week because it has come off patent and two, slightly cheaper, yellow-pack drugs are coming on the marketSNL's advice is to threaten your doctor until he prescribes for you.

No comments: