Superbugs are outpacing science and economics in drug-resistance war

Print 17 June 2016
Mari Serebrov / BioWorld

A House subcommittee confronted the consequences of kicking the antibiotics can down the road, as lawmakers delved into the U.S. response to the growing global emergence of superbugs.

Spurred by the discovery last month that a Pennsylvania woman had an E. coli infection with the rare MCR-1 gene that makes the bug resistant to the last-resort antibiotic colistin, members of the Energy and Commerce Subcommittee on Oversight and Investigations quizzed federal officials Tuesday on what's being done to get in front of the growing resistance to available drugs.

Their questions were doused in urgency, given the significance of finding the colistin-resistant E. coli strain in the U.S. First detected a year ago in a few people and pigs in China, the MCR-1 gene exists on a small piece of DNA that can move from one bacteria to another, spreading antibiotic resistance. While the E. colistrain itself isn't resistant to all antibiotics, the fear is that the gene could pass to carbapenem-resistantEnterobacteriaceae, which are resistant to most drugs, knocking out the last line of defense against the deadly bugs.

"Concerns about this new threat are real. . . . It signals the arrival of a new unstoppable superbug," said Energy and Commerce Committee Chairman Fred Upton (R-Mich.). It's a matter of when, not if, the resistant strains will combine, he predicted, adding, "the end of the road isn't far away for antibiotics."

DECADES BEHIND

The superbugs are always a step ahead of the research, the FDA's Janet Woodcock told the lawmakers. Unfortunately, the development of an arsenal of new antimicrobials is decades behind due to economic and scientific barriers, she said.

Several drugmakers closed down their antimicrobial research years ago because the economic incentives weren't there due to the drugs' limited use in the market, Woodcock said. Instead, companies focused their resources on other public health issues such as HIV and cancer.

While drug resistance was a future possibility at the time, developing new antimicrobials wasn't a front-burner priority. Since then, the growing pressure to reduce antibiotic use, the mounting resources required to develop a new drug and the difficulty of the science involved have further weakened the antimicrobial pipeline. Woodcock said the chance of getting a new antimicrobial from discovery to approval is "one in thousands." If the drug makes it to clinical development, the chance improves to one in 10.

Today, the focus is on developing not only new antibiotics, but also rapid point-of-care diagnostics to ensure the proper use of the drugs, alternative treatments including medical devices, and research into what makes a bug resistant and how that resistance can be transmitted globally in the space of a year.

Despite the urgent need, it could take years to develop a broad, robust pipeline to combat the bugs. That will be too late for some. Subcommittee Chairman Tim Murphy (R-Pa.) noted that without action, the global annual death toll from drug-resistant infections could reach 10 million by 2050. Currently, 23,000 people die in the U.S. and up to 700,000 die globally each year from antibiotic-resistant infections.

FINGER POINTING

While the lawmakers agreed that the superbugs can't continue to be kicked down the road, they did a lot of finger pointing – at doctors who needlessly prescribe antibiotics, patients who demand the drugs for viral infections, livestock producers who use them to spur animal growth, and drug and device companies that turned away from the space.

Rep. Diana DeGette (D-Colo.) even blamed the Senate for not yet passing the 21st Century Cures Act, which she is co-sponsoring. The bill, which was passed by the House nearly a year ago, includes economic incentives for the development of new antimicrobials and would allow the FDA to approve the drugs for a limited population based on streamlined trial designs. (See BioWorld Today, July 13, 2015.)

Woodcock said the current clinical development scheme doesn't work well for drugs aimed at treating superbugs. It is difficult to enroll enough patients in the trials, since infected patients must be treated immediately. The limited population approval could address some of those issues.

Some lawmakers fingered other countries. "This is a global threat," said Rep. Frank Pallone (D-N.J.). The fight against superbugs will be only as "strong as the weakest link," he added, citing the need for global surveillance on the emergence of new drug-resistant bugs.

Rep. David McKinley (R-W.Va.) pointed out that the U.S. accounts for only 5 percent of the world's population.

He wondered how improved stewardship of antimicrobials in the U.S. would make a difference when antibiotics are sold over-the-counter and rampantly overused in other countries.

Beth Bell, of the Centers for Disease Control, agreed that some countries have far more drug resistance. In India and other hot spots, colistin, which can be toxic to the kidneys and brain, is heavily used because it's all that's left in their arsenal. That's why health officials have to treat superbugs both domestically and globally, she said.

In blaming the superbug on drug companies that walked away from the space, Rep. Janice Schakowsky (D-Ill.) said, "It sets my hair on fire" to hear that drug companies are unwilling to address this public health problem because there's not enough money in it.

She also blamed TV drug advertising, saying it makes patients "think they're in charge" so doctors have to give them the drugs they want.

Richard Hatchett, acting director of the Biomedical Advanced Research and Development Authority (BARDA), countered that drug companies have to at least be able to break even.

BARDA is helping small companies in the antimicrobial space with stockpile buys, incentives and development tools.

BARDA also is expanding its partnerships with private companies to spur investment in vaccines, diagnostics and therapies to treat and prevent superbug infections. But it will take years for those investments to mature, Hatchett said, adding that industry must see sustained government commitment in that area before it will view the government as a reliable partner.

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