Thursday, Nov. 5, 2009 | It is called Clostridium difficile, and it is a particularly devious bacteria that can turn a run-of-the-mill infection into a life-or-death struggle.
C. diff, as it is known, can be just another bug among the plethora of bacteria engaged in a constant state of battle in a person’s lower intestine. But if a person has C. diff in their system and needs an antibiotic — it could be for something as innocuous as a urinary tract infection or an infected wound — things can get much worse.
That’s because C. diff, a so-called superbug, is resistant to almost all forms of antibiotics. So when the antibiotic kills the other bacteria that have held C. diff at bay, it ends up all alone and free to spew its toxin. It carries the potential to destroy a patient’s intestines and, in the worst cases, kill them.
“What is scary is that [C. diff] has gone from being a disease that we used to see occasionally in nursing facilities before 2005 to something that is a huge problem,” said Frank Myers, director of clinical epidemiology and safety systems at Scripps Mercy Hospital.
Superbugs like C. diff, and the well-known Methicillin-resistant Staphylococcus aureus, or MRSA, are now among our largest infectious disease threats. They annually infect millions of people worldwide and kill tens of thousands in the United States — more than the AIDS virus — according to a recent Centers for Disease Control and Prevention study.
But because antibiotics do not generate massive profits like drugs that target chronic diseases, large pharmaceutical companies have in recent decades cut back significantly on their once-robust antibiotic programs. So the fight has largely been left up to small biotechs, including San Diego-based companies like Optimer Pharmaceuticals, Trius Therapeutics and Mpex Pharmaceuticals.
“The beauty of antibiotics is that they cure people,” said Joshua Fierer, a University of California, San Diego professor of medicine and chief of infectious diseases at the VA Medical Center, San Diego. “But from an economic standpoint, when you cure someone, you lose the revenue they generate.”
Of the top 20 selling pharmaceuticals, only one is an antibiotic, Fierer said. A study this year by the London School of Economics and Political Science said that because people stay on antibiotics for a limited time and are cured once they’re off, drug companies’ marketing costs increase and expected returns on investment decrease.
“There is still potential for money to be made on antibiotics, but not on the scale of a cholesterol drug,” said Alan Carr, a pharmaceutical industry analyst for Needham & Company, an investment banking firm. “You are talking in the hundreds of millions.”
That’s chump change compared to the billions that a cholesterol drug like Pfizer’s Lipitor generates, Carr said, but a “perfect opportunity for biotechs.” Doctors like Myers and Fierer hope the lure of profits will bring more drugs to the market and slow the rate of infections caused by antibiotic resistant bacteria. But that’s not the case now.
“There are just too few drugs in the pipeline,” Fierer said. “We find ourselves in a paradox — the more effective a drug is, the more it is used. And the more it is used the more resistant the bacteria become.”
Optimer has been working on a drug that attacks C. diff, called Fidaxomicin, for most of the past decade, and hopes to have U.S. Food and Drug Administration approval by 2011, said company CEO Michael Chang. The company is confident that Fidaxomicin will be approved, Chang said, but he added that developing antibiotics can be very difficult.
While it is easy to identify bacteria that are resistant to antibiotics, it is hard to figure out why or how exactly they are resistant. And in order to get FDA approval, Chang said, companies have to show that their drug attacks the resistance and cures the patient.
“With diabetes you don’t have to cure the patient, you just have to show that your drug lowers blood sugar,” Chang said. “With antibiotics you have to show a cure.”
Ironically, the more than half-trillion dollar pharmaceutical industry was largely built on antibiotics. From the 1940s, when penicillin was first mass produced, until the 1970s, bacteria killers were the focus of the majority of Big Pharma’s research and development and the source of most of its revenues.
By the 1980s, however, investment in antibiotics by large pharmaceutical companies had slowed dramatically. By the early 1990s, say Fierer and others, Big Pharma had all but pulled out of the antibiotics business and shifted to treatments for chronic diseases from high blood pressure, to diabetes to schizophrenia — diseases whose sufferers are often customers for life.
Meanwhile, the bacteria that were supposedly beaten began developing resistance to antibiotics. It happened slowly at first. In the early 1990s, only a handful of hospital patients per thousand were contracting MRSA, which often begins as a skin infection but can lead to deadly pneumonia. That small handful was all it took for the once rare problem to eventually spread and become an epidemic.
And while the bacteria fighters continue to try to gain the upper hand on MRSA and C. diff, the next generation of superbugs loom. MRSA and C. diff are in a class of bacteria known as gram positive, which have a single cell membrane. However, in recent years hospitals have begun reporting infections caused by gram negative bacteria.
Gram negative bacteria have two cell walls and are much harder to kill. And though deadly gram negative respiratory infections are increasingly showing up in patients in hospitals and nursing homes, “there is remarkably little work going on in [clinical research] against those,” said Carr, the industry analyst.
Mpex, however, is one company focusing on the next generation, said CEO Dan Burgess. The company just reported positive clinical results of its product, Aeroquin, which targets infections from gram negative bacteria in patients with cystic fibrosis.
“There is a greater recognition that we can’t shut down antibiotic programs because the bugs will keep evolving,” Burgess said. “But there are challenges to identifying where the next major problem will be, and being there in time.”