We're in Dire Need of New Funding for Antibiotics, Researchers Say
Antibiotic resistant infections are scarier than ever, but many pharmaceutical companies are neglecting antibiotics R&D. A new editorial proposes some solutions.
MRSA. Image: NIAID
As a global community, we're in a high-stakes race against rapidly developing antibiotic resistance—and we're losing.
Each year, 23,000 Americans die from antibiotic resistant infections, according to the Centers for Disease Control and Prevention. Epidemiologists agree that number is only going to increase. Just in the past week, a drug-resistant bacteria called carbapenem-resistant Enterobacteriaceae (CRE) has been linked to four deaths in California and North Carolina.
"A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century," the World Health Organization urgently stated last year in a sweeping report on the global state of antimicrobial resistance.
With antibiotic-resistant infections growing more prevalent, we're hurtling towards a world in which the antibiotics we have are becoming obsolete. But as the threat of antibiotic resistance looms larger and larger, many pharmaceutical and biotech companies are headed in the opposite direction, pushing fewer antibiotics into the pipeline than before. Between 2008 and 2012, the Food and Drug Administration approved only two systemic antibiotics, compared to 16 from 1983 to 1987.
In an editorial published yesterday in Science, researchers at Harvard University call for new strategies to incentivize antibiotic development. In particular, they argue for policies that reimburse antibiotics with high social value, namely those that reduce morbidity, prevent mortality and increase quality of life.
"One important way we can encourage development of antibiotics is to make sure the payment of them is commensurate to their public health benefit," said Aaron Kesselheim, a professor of medicine at Harvard Medical School, and one of the authors of the essay. "If a new antibiotic comes out and clinical trials demonstrate it's better at treating resistant infections, then we should be prepared, and have the systems in place, to appropriately reimburse that medicine."
In the paper, the authors cite a $500 million gap between the societal benefits of a new antibiotic that treats life-threatening bacterial illnesses and the actual returns it brings in for a manufacturer. They think federal reimbursements through programs like Medicare and Medicaid can help close that gap.
Kesselheim and his co-authors hone in on financial incentives for good reason: it's not easy to make a profit off antibiotics in the current market, particularly compared to other products, such as cancer or hepatitis C drugs, that people think of as life-saving and therefore fetch a much higher price.
Antibiotics don't operate under normal market conditions, said Kevin Outterson, a professor of law at Boston University who has written about incentivizing antibiotic development. For one, companies can't just try to sell as many antibiotics as possible because they have to consider antibiotic resistance. The more a drug is used, the less effective it will become over time.
The FDA approval process is unwieldy too. Companies have to run large clinical trials demonstrating that their product stacks up against existing competitors. Consider what it would be like to sell iPhones the way antibiotics are sold, said Outterson.
"Say you want to sell a new product, an iPhone 7, in the normal world. Before you can sell, you have to prove to experts that the iPhones 3 through 6 are all worthless," he said.
Lastly, Outterson pointed out, antibiotics have modest price tags. "There are a dozen cancer therapies that are more than $100,000 for a course of treatment, despite very modest proof of efficacy," he said. "Meanwhile a course of new antibiotics costs something like $2-3,000 dollars."
"This is a very slow moving train wreck that continues to grow."
On top of that, he said, new antibiotics have to compete with generic products, which still work pretty well most of the time and cost closer to $100.
"Overall, you have low volumes, and low prices," said Outterson. "That's a bad system."
Competition with generics and determining appropriate levels of use in the context of mounting antibiotic resistance are among the key challenges pharmaceutical and biotechnology companies must face when developing antibiotics, said Elizabeth Cobbs, executive director of health technology assessment strategy at Merck, which ranks as the second-largest American pharmaceutical company after Pfizer.
Cultural factors come into play too, said Cobbs. "There are certain products, like antibiotics and vaccines, that people are more likely to think of as a public good," said Cobbs. These societal perceptions are one of many factors that can affect how antibiotics get priced, she said.
This past winter, Merck acquired Cubist Pharmaceuticals, which specializes in antibiotic development, for $9.5 billion. These changes at Merck are part of a broader shift, said Cobbs. (Full disclosure: My dad is a global health strategist at Merck, but didn't speak to this story.)
"The general public dialogue around these issues has really come to a new era. A lot of government bodies, the WHO for example, are coming out with statements about antibiotics and the lack of new products being investigated," she said.
Over the past year, world leaders have brought up the issue time and again. In January, President Obama announced that he wants to double the amount of federal funding dedicated to fighting antibiotic resistance. Last summer, Prime Minister David Cameron called for increased efforts in the UK, cautioning that antibiotic resistance could cast the world "back into the dark ages of medicine."
The greater political visibility is promising, said Kesselheim, but the federal government needs to back its words with more investment in basic research. "The problem with antibiotic development is about lack of ideas coming into the pipeline," he said. "The next policy intervention would be greater investment in academic research that identifies new mechanisms of action for antibiotics."
For an industry-wide transformation, major policy changes need to happen sooner rather than later, agreed Outterson. "Yes, there are bills being discussed and studies are coming out, including this new report in Science," he said. "These are all great ideas. Now we need actual implementation—in months, not years."
For now, antibiotic resistance is killing people in pockets. Episodes like the recent CRE outbreaks crop up, but stay relatively contained within the hospitals they originated in. But we can't afford to ignore building resistance, warned Outterson.
"This is a very slow moving train wreck that continues to grow," he said. His biggest concern is that we will find ourselves unprepared to deal with a bacterial illness outbreak on the scale of the Ebola virus outbreak last fall.
"We can't wait until that happens in a major US city. The economic and humanitarian costs would be astronomical," he said. "We need protections against these types of bacteria, and those protections have to be ready—not an idea in the lab, but a product."