he Food and Drug Administration is reviewing a drug that mops up bacterial toxins while leaving microbes themselves unscathed, potentially providing infectious disease doctors with a new treatment option that might be less prone to drug resistance than existing antibiotics.
It’s the first in a new wave of targeted therapies that home in on the bacterial poisons responsible for the abdominal pain, vomiting, and watery diarrhea experienced by people with gut infections. Although doctors expect to use this first antitoxin in combination with conventional antibiotics, it demonstrates that a soft touch can help ward off persistent bugs.
“It’s really exciting,” said Dr. Nicholas Kartsonis, section head of infectious diseases clinical research at Merck, the drug company behind the agent. Merck announced this week that the FDA had accepted its marketing application, and that a regulatory decision is expected by the end of July. “This is really getting people enthused about working on nonantibiotic approaches to treating infections.”
Other companies pursuing their own antitoxins against deadly pathogens include AstraZeneca and Aridis Pharmaceuticals, each of which are developing experimental drugs that neutralize a Staph toxin, and Bellus Health, which is working on a drug that blocks the E. coli toxin.
Doctors warn that these agents, if approved, are likely to be come with a much higher sticker price than existing antibacterials. This is because drug companies need to make profits and recoup their drug development costs, but also because these drugs are “biologic” antibodies that are expensive to produce.
Infectious disease specialists urgently need new drug options — and the situation is especially dire in the fight against Clostridium difficile, the most common type of hospital-acquired superbug.
C. diff, as it’s commonly known, lays low nearly half a million Americans and kills an estimated 15,000 each year.
Merck’s first-in-class drug targets one of the two toxins produced by C. diff. Although bacteria-killing antibiotics can get these infections under control, more than 25 percent of patients get a second bout of C. diff within weeks of their recovery. And for many patients the infections keep on coming back after that. “It’s a vicious cycle,” Kartsonis said.
Merck showed in clinical trials that when patients used their toxin-blocking agent in combination with traditional antibiotics, only 16 percent of patients got sick again, with few noticeable side effects of the experimental therapy.
If used widely, the Merck drug, called bezlotoxumab, could help ward off tens of thousands of recurrent infections in the United States each year. “This would be a welcome addition to our medicine box,” said Dr. John Lamont, a gastroenterologist at Beth Israel Deaconess Medical Center in Boston who specializes in intestinal infections and was not involved in the development of the drug.
But with one in six patients still experiencing recurrences, Lamont noted, “it’s not a home run.”
Bezlotoxumab could make a bigger public health dent if it can be used to stop C. diff from taking hold in the first place in at-risk patients. “Theoretically this might work,” said Lamont.
Merck has not yet tested this prophylactic strategy, but AstraZeneca is already running a trial of its Staph antitoxin agent to see if it can prevent infections in people on ventilators. These assisted-breathing devices are known to put people at a heightened risk of developing Staph-related pneumonia.
Still, Dr. David Shlaes, a retired antiinfectives consultant, cautioned that these drugs will only solve a small piece of the drug resistance problem. “I’m not sure that this is the answer to the bigger resistance problem,” he said.
Even more effective drugs, and better stewardship of antibiotics in humans and livestock, are also needed to manage the emerging crisis of antibiotic resistance.