All those people who wished there were no drug companies competing to make the best treatments are getting their wish. That means universities, which are not used to doing applied research, could now be tasked with trying to fill the void left by the private sector. Can the current university system do it? As a famous jab at the National Institutes of Health by Samuel Broder, former Director of the National Cancer Institute, put it, "If it was up to the NIH to cure polio through a centrally directed program instead of independent investigator driven discovery, you'd have the best iron lung in the world, but not a polio vaccine."
Fixing problems is not the strong suit of academics, that is why 60 percent of America's research is still done in the private sector. Government-funded work requires a different mentality than working at a drug company where the goal is producing medicine.
The Centers for Disease Control and Prevention says that at least 2 million Americans are sickened by antibiotic resistant infections each year and 23,000 die. That means in the time it took one high-profile ebola patient to die earlier this month, 442 Americans died due to antibiotic resistance.
Michael Kinch, PhD, associate vice chancellor and director of the Center for Research Innovation in Business at Washington University in St. Louis, had a son sickened by antibiotic resistance. Prior to that he was managing director of the Center for Molecular Discovery at Yale University and had assembled a huge database of information about drug discovery and development in the pharmaceutical industry.
In an article in Drug Discovery Today, Kinch summarized the financial constraints that have led to the current crisis in antibiotic supply. The number of antibiotics available for clinical use, Kinch said, has declined to 96 from a peak of 113 in 2000. The rate of withdrawals is double the rate of new introductions and antibiotics are being withdrawn because they don’t work anymore, because they’re too toxic or because they’ve been replaced by new versions of the same drug. Introductions are declining because pharmaceutical companies are leaving the business of antibiotic discovery and development.
Pfizer or its predecessors developed 40 of the 155 antibiotics ever sold in this country but is no longer in the antibiotic space. Eli Lilly, AstraZeneca and Bristol-Myers Squibb have also left the antibiotic field, which is now dominated by small companies that focus on drugs for resistant bacterial infections that could have higher price points.
The big reason pharmaceutical companies are withdrawing is that government rules and patent law squeeze them for time. A patent gives a company 20 years of protection for a new drug, but it takes 11 years of clinical trials (on average) to get a drug approved. That means the typical company has just 9 years under patent to earn back the development costs before a generic comes in and offers it at lower cost and everyone cheers that greedy companies can't charge so much - which is fine, unless the companies all leave. It's echoes of the steel industry in the early 1970s, when everyone claimed that if steel and auto companies were making any profit, they were not in distress. Today, there is basically no domestic steel industry in America, and it once employed millions.
With an antibiotic, there is an additional medical catch. Because of rising resistance doctors hold new antibiotics in reserve, using them only in cases of dire need. This happened, for example, in the case of vancomycin, which has long been used as a drug of last resort.
“When you hold a drug in reserve,” Kinch said, “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.”
Companies have decided there is no exit from this trap – let the government do it and they can deal with their own bureaucracy.
People think that the NIH can solve problems like this, but the NIH budget, which doubled during the Bush administration, has been static ever since. In constant dollars it is below 2009 levels and Johns Hopkins University made lots of new buildings with the $1 billion they get each year, but they are not designed to produce drugs.
Academics are blaming Republicans for the decline - the same political party that doubled their funding over Clinton - and the Obama administration is happy to let them, but being hyper-political is not the answer.
Kinch says the answer is “de-linkage,” finding a way to disconnect the costs of development from the sale of pills. Some have suggested that large prizes, of $1 billion or more, be offered for the development of new drugs, which would then be sold for modest prices by other companies.
That would be a bargain. We could offer a $1 billion prize to develop the iPhone 8 also and give them away for free - if we believe that products actually get developed that way.
But if the government takes over antibiotics, they have to cut their own red tape - they can fast-track every ebola product and academics are suddenly saying clinical trials are overrated when the crisis is getting media coverage, so the same could be done for antibiotics. Army personnel can't sue the Army if a medical procedure goes bad and the government could exempt itself from lawsuits related to antibiotics.
The Infectious Diseases Society of America (ISDA) has launched a “10 x 20” initiative whose goal is to create global antibacterial drug research-and-development enterprise with the power in the short-term to develop 10 new, safe and effective antibiotics by 2020. Britain is offering a prize of £10 million, called the Longitude Prize 2014 (after the prize once offered for an accurate way to determine the longitude of ships at sea), for a rapid test that would allow health professionals to identify bacteria quickly and so administer only the right antibiotics at the right time.
Washington University does a lot of research on the human microbiome, the trillions of organisms that live in our guts, many performing beneficial tasks such as digesting food and fighting off infections. Why is that relevant? In the past the hunting ground for new antibiotics was often the soil. Vancomycin, for example, was found in a soil sample from Borneo. But in the future, the hunting ground may become the natural products produced by the human microbiome.
Antibiotics are not the only drug class heading for trouble—Kinch mentions that HIV/AIDs drugs are following a similar trajectory—but they have become the poster child for the larger problem of drug discovery and development in part because they underpin every part of modern medical practice, from surgery to cancer treatment and pretty much everything in between.
Source: Washington University in St. Louis
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