We'd like to think that as the antibiotic crisis worsens and the corresponding death toll rises, drug research is going full-steam ahead. Supply and demand, right? If only.
Setting aside a certain high-mortality viral infection, antibiotic resistance might rank at or very near the top of the popular imagination's disease doomsdays. In the very near future, the doomsaying goes, our antibiotics will stop working and civilization will be abruptly returned to the bacterial dark ages.
A cut or scrape in this regressed world could mean a death sentence, as any bacterial infection might now find itself unimpeded, like a match in a pile of dry leaves. Sepsis here is always just a minor accident away.
But even a complete loss of antimicrobal capabilities wouldn't really look like that; the impact of antibiotics, while enormous, is usually overstated. Yet the fear is real and pervasive. So we might expect that drug companies are working overtime to ensure that we're never actually confronted with a return to the pre-antibiotic days. Supply and demand, right?
Unfortunately, supply and demand as it pertains to the pharmaceutical industry isn't what it may seem. According to a new report in Drug Discovery Today, courtesy of Washington University in St. Louis professor Michael Kinch, the general trend is for drug companies to withdraw from the antibiotic market completely, a situation that's poised to exacerbate the whole antibiotic crash in potentially very dangerous ways.
As it stands today, antibiotics are leaving the marketplace at a rate twice that of new drugs entering it.
The antibiotic arsenal circa 2000 consisted of 113 drugs, and it's since fallen to just 96.
"Obsolescence and resistance has eliminated one-third of these drugs," Kinch writes in the current study. "Consequently, the arsenal of antibiotics peaked in 2000 and is declining. Likewise, the number of organizations awarded at least one [new molecular entity] (NME) for a bacterial indication has declined to a level not seen in more than a half century."
The antibiotic arsenal circa 2000 consisted of 113 drugs, and it's since fallen to just 96, a trend poised to continue on into the future.
Antibiotics are usually withdrawn, according to Kinch, because they've stopped working, are too toxic, or because they've been replaced by a newer version of the same drug (a popular Big Pharma practice in which a compound is tweaked in some mostly insignificant way so it can get re-patented).
Pfizer, the pharmaceutical giant responsible for 40 of the 155 antibiotics ever sold in the United States, has exited the market completely, joining other big names like Eli Lilly, AstraZeneca, and Bristol-Myers Squibb. As much as many of us love to hate Big Pharma, that exit is bad news.
In the wake of these giants, we have pharmaceutical startups, like Cubist, that exist specifically to attack the antibiotic resistance problem. The resources aren't quite the same, however: Cubist, for example, just released its second new drug in 20 years.
Pharma-spotters won't be terribly surprised by this market abandonment. This is an old and fundamental problem with how drug research is conducted, generally.
Drug companies, after all, aren't altruists because they're drug companies, e.g. entities that exist to make money. And the big bucks aren't in antibiotics, at least compared to highly marketable (read: marketable as in direct-to-consumer, "ask your doctor about ...") drugs for quitting smoking, unsatisfactory erections, and most anything that can be directed at the captive, high-value market of retired baby boomers.
In part, Kinch sees it as a problem arising from patent law, though he doesn't seem to outright blame patent law. Developing and testing a new drug takes an average of 11 years, he says, while the drug's patent expires after 20, leaving just nine years for the drug manufacturer to recoup its investment and turn a satisfactory profit. Because of increasing drug resistance, new antibiotics in particular are often held in reserve by doctors and used only as a drug of last resort.
So, it's something of a catch-22. A company produces a drug designed to surpass the current level of antibiotic resistance and then can't sell much of it because doctors are justifiably concerned about that resistance. By the time said drug becomes a first-line treatment, it might as well be generic. We'd all love for that to not matter and have our drug-makers be in it for the greater good, but such is the weird, unsavory drug development system we've created and allowed to perpetuate.
"When you hold a drug in reserve," Kinch said in a WUSTL statement, "you're eating into the patent time a company has to recoup its development costs. If you've got this vancomycin-like situation, where the drug is sitting on a shelf—quite literally sitting on a shelf—how is a company going to make its money back? It can't price the drug at $10,000 a dose."
Given that antibiotic resistance affects pretty much all of us, hitching drug development to profit-potential seems actually insane.
The answer, Kinch suggests, is a thing that we really should have been pushing for all along: moving the research into universities, or the public sector generally. The NIH is a nice idea, but its budget has been in a nosedive since 2009. A functional Washington, DC is probably not a thing anyone should be holding their breath for, particularly when it comes to a rapidly-advancing health crisis such as antibiotic resistance.
The overaching goal should be what's known as "de-linkage," a world in which the development costs of a pharmaceutical drug are disconnected from the sales of that drug. Given that antibiotic resistance affects pretty much all of us, hitching drug development to profit-potential seems actually insane. (As an aside, when you hear so and so talking about "letting the market handle it," this is what that looks like.)
Kinch calls this gap between the lab and market the "valley of death," the place where potentially lifesaving drugs waste away because of insufficient profit potential.
One interesting suggestion for moving drug research away from Big Pharma and Kinch's valley of death involves drug discovery prizes. One example is the UK's £10 million Longitude Prize 2014, which will be awarded to whoever can come up with a rapid test for differentiating between bacterial infections.
Imagine if a prize of, say, $1 billion was offered per unique new antibiotic. The antibiotic's creator gets the award, while the manufacturing and marketing of the drug is handed over to some other company, which sells it for a "modest" price.
At the very least, it should be clear we're in an unsustainable place. There are indeed a whole lot of new, extremely promising ideas out there for beating antibiotic resistance, but the marketplace still looms, ready to snatch away those good ideas and exile them to the valley of pharmaceutical death.