 "No new antibiotic since the 1980s!")
There is clearly something wrong with pharmaceutical innovation. Antibiotic-resistant infections sicken more than two million Americans every year and kill at least 23,000. The World Health Organization has warned that a "post-antibiotic era" may be upon us, when "common infections and minor injuries can kill." Yet the enthusiasm of the pharmaceutical industry for developing drugs to combat such a potential disaster might be best characterised as a big collective "meh."
No major new type of antibiotic has been developed since the late 1980s, according to the WHO From 2011 to 2013, the Food and Drug Administration approved only three new molecular entities to combat bacterial diseases - the lowest rate since the 1940s.
And this is hardly the drug industry's only problem. Antibiotics, Michael S Kinch, who led a team at the Yale Center for Molecular Discovery tracking the evolution of pharmaceutical innovation over the last two centuries, told me, "are the canary in the coal mine." This is particularly striking at a time when the pharmaceutical industry is unusually optimistic about the future of medical innovation. So far this decade, the FDA has approved drugs at a pace second only to the 1990s. But the economics of the drug development, argues Kinch, are not conducive to creating the highest levels of public health. More and more antibiotics are going out of circulation every year - either because bacteria have become resistant to them or because they have been replaced by better or less toxic drugs. The pharmaceutical arsenal against bacterial infections shrank to only 96 different molecules by the end of last year, 17 fewer than at the turn of the century.
Nevertheless, many of the big drug companies that produced the antibiotic breakthroughs of the past have decided to drop this line of research. And few new entrants are jumping in. "It has become very difficult to find new drug classes to fight infections," Dolsten of Pfizer acknowledged. "There haven't been enough incentives for the industry to take on 10 or 15 years of research." Antibiotics face a daunting proposition. They are not only becoming more difficult to develop, but they are also not obviously profitable. Unlike, say, cancer drugs, which can be spectacularly expensive and may need to be taken for life, antibiotics do not command top dollar from hospitals. What's more, they tend to be prescribed for only short periods of time.
Antibiotics are not the only drugs getting the cold shoulder, however. Research on treatments to combat HIV/AIDS is also drying up, mostly because the cost and time required for development are increasing. Neuropsychiatric diseases, including Alzheimer's and depression, are the leading cause of disability across most of the industrial world. And they are going to get worse. Yet researchers have underscored a dearth of investment into these.
Instead, pharmaceutical and biotechnology firms are mostly targeting specific varieties of cancers - and drugs for so-called orphan diseases, which affect very small populations. "More people are studying orphan diseases than have orphan diseases," Kinch said jokingly. Of the new drugs that the FDA approved in 2013, about 70 percent were specialty drugs - which are used by less than 1 percent of the population, according to the drug benefits manager Express Scripts.
The problem, of course, lies in the industry's incentives. The cost of developing a new drug has skyrocketed over the last three decades. A research paper by scientists from Eli Lilly suggested that in 2010, it cost $1.8 billion to bring a big new drug from conception to rollout, through the costly gantlet of clinical trials needed to prove that it is both safe and more effective than existing therapies.
Developing orphan drugs is cheaper. Clinical trials are inherently less expensive because the drugs are aimed at a small population. "Companies are flocking to rare diseases," said John LaMattina, a former head of research at Pfizer. "They might only make $500 million in sales a year, but their costs are much lower."
Tweaking the existing system might be a more feasible proposition. Research on new antibiotics could be encouraged by allowing shorter clinical trials for the promising molecules or guaranteeing minimum returns for groundbreaking drugs. Patricia Danzon of the Wharton School of the University of Pennsylvania suggests recalibrating the regulatory burden to favour research in drugs with a broader potential footprint. At the same time, new mechanisms are needed to constrain prices. "There's a myth in the United States that market forces are working to control prices," Danzon said. It's clear that they aren't. But the market isn't delivering the innovation we need, either.
No major new type of antibiotic has been developed since the late 1980s, according to the WHO From 2011 to 2013, the Food and Drug Administration approved only three new molecular entities to combat bacterial diseases - the lowest rate since the 1940s.
And this is hardly the drug industry's only problem. Antibiotics, Michael S Kinch, who led a team at the Yale Center for Molecular Discovery tracking the evolution of pharmaceutical innovation over the last two centuries, told me, "are the canary in the coal mine." This is particularly striking at a time when the pharmaceutical industry is unusually optimistic about the future of medical innovation. So far this decade, the FDA has approved drugs at a pace second only to the 1990s. But the economics of the drug development, argues Kinch, are not conducive to creating the highest levels of public health. More and more antibiotics are going out of circulation every year - either because bacteria have become resistant to them or because they have been replaced by better or less toxic drugs. The pharmaceutical arsenal against bacterial infections shrank to only 96 different molecules by the end of last year, 17 fewer than at the turn of the century.
Nevertheless, many of the big drug companies that produced the antibiotic breakthroughs of the past have decided to drop this line of research. And few new entrants are jumping in. "It has become very difficult to find new drug classes to fight infections," Dolsten of Pfizer acknowledged. "There haven't been enough incentives for the industry to take on 10 or 15 years of research." Antibiotics face a daunting proposition. They are not only becoming more difficult to develop, but they are also not obviously profitable. Unlike, say, cancer drugs, which can be spectacularly expensive and may need to be taken for life, antibiotics do not command top dollar from hospitals. What's more, they tend to be prescribed for only short periods of time.
Antibiotics are not the only drugs getting the cold shoulder, however. Research on treatments to combat HIV/AIDS is also drying up, mostly because the cost and time required for development are increasing. Neuropsychiatric diseases, including Alzheimer's and depression, are the leading cause of disability across most of the industrial world. And they are going to get worse. Yet researchers have underscored a dearth of investment into these.
Instead, pharmaceutical and biotechnology firms are mostly targeting specific varieties of cancers - and drugs for so-called orphan diseases, which affect very small populations. "More people are studying orphan diseases than have orphan diseases," Kinch said jokingly. Of the new drugs that the FDA approved in 2013, about 70 percent were specialty drugs - which are used by less than 1 percent of the population, according to the drug benefits manager Express Scripts.
The problem, of course, lies in the industry's incentives. The cost of developing a new drug has skyrocketed over the last three decades. A research paper by scientists from Eli Lilly suggested that in 2010, it cost $1.8 billion to bring a big new drug from conception to rollout, through the costly gantlet of clinical trials needed to prove that it is both safe and more effective than existing therapies.
Developing orphan drugs is cheaper. Clinical trials are inherently less expensive because the drugs are aimed at a small population. "Companies are flocking to rare diseases," said John LaMattina, a former head of research at Pfizer. "They might only make $500 million in sales a year, but their costs are much lower."
Tweaking the existing system might be a more feasible proposition. Research on new antibiotics could be encouraged by allowing shorter clinical trials for the promising molecules or guaranteeing minimum returns for groundbreaking drugs. Patricia Danzon of the Wharton School of the University of Pennsylvania suggests recalibrating the regulatory burden to favour research in drugs with a broader potential footprint. At the same time, new mechanisms are needed to constrain prices. "There's a myth in the United States that market forces are working to control prices," Danzon said. It's clear that they aren't. But the market isn't delivering the innovation we need, either.
© 2014 The New York Times