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Follow the money: Why few new drugs in pipeline

Only five of 400 upcoming drugs are antibiotics

Though some new antibiotics are coming on to the market, the pipeline is at a mere trickle in a vast desert of resilient, resistant bugs. As a result, more drastic strategies may be needed, including economic incentives for the development of "orphan drugs" banning antibiotics as animal growth promoters, and "saving" a newly developed drug as a proverbial ace in the hole, a panel of experts noted recently.

"Why are there so few antibacterials developed? It’s clearly an issue of money," said Martin Blaser, MD, chairman of the department of medicine and professor of microbiology, at the New York University School of Medicine in New York City. "The pharmaceutical industry is obliged to their stockholders to maximize their profits."

Blaser spoke at press conference on antibiotic resistance at the New York Academy of Sciences on antibiotic resistance April 30, 2003. The event — which was largely a warning that too little is being done about the problem — was jointly sponsored by the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, and the Society of Infectious Diseases Pharmacists.

In general, the most profitable antibacterial drugs are broad-spectrum antimicrobials that will be used widely for a variety of pathogens.

"It’s increasingly difficult to develop broad-spectrum antibiotics," Blaser said. "It is possible to develop antibiotics against specific organisms, against specific targets, but then the markets are very small. So if we want to keep ahead of the bacteria, as a matter of public policy, we have to find ways to encourage companies to develop, in essence, orphan [e.g., unprofitable] drugs, and the FDA [U.S. Food and Drug Administration] Orphan Drug Act is doing that, but probably not sufficiently."

As a result, there were no antibacterial agents in the 89 new drugs approved by the FDA in 2002. A survey of the 11 major pharmaceutical companies, showed that only five of 400 new drugs in the development pipeline are antibacterial, he added. Yet — as infection control professionals scarcely need to be reminded — vancomycin-resistant Staphylococcus aureus (VRSA) made its dreaded debut last year and methicillin-resistant S. aureus (MRSA) is now becoming a community-acquired pathogen. The antibiotic pressure to create these bugs is immense.

"The average child in the United States, by the age of 15, has received four courses of antibiotics just for the treatment of otitis media," Blaser said. "That’s enormous pressure. What’s the consequence? When you treat someone with an antibiotic, it affects not only the ear in this case, but all the bacteria in the body. So our respiratory flora are becoming increasingly resistant to antibiotics."

For example, 40% of pneumococci — a pathogen once completely susceptible to penicillin — is now resistant to the drug. In addition, for decades the food industry has been feeding tons of antibiotics to farm animals as growth promoters. The practice has been banned in some countries as evidence mounts that it selects out for resistant bugs, but it continues unabated in the United States. Why does the practice continue? Again, follow the money.

"There are important interests that want to keep antibiotics in food animals," he said. "The two interests are pharmaceutical companies that sell them, and the food industry that wants to produce food at the lowest cost. It becomes a question of public policy. In Scandinavia and England, the public has weighed in on this, and has said, We’re willing to pay the extra costs,’ which in fact are quite marginal. If we banned antibiotics from use in the poultry industry, the price of poultry at the marketplace would probably go up 1 or 2 cents a pound."

The other side of the ledger

Meanwhile, the United States is spending some $4.5 billion annually to treat drug-resistant infections.

"That’s just in direct costs," said Neil Fishman, director of the department of health care epidemiology and infection control at the University of Pennsylvania Medical Center in Philadelphia.

"About 19,000 people die annually of resistant infections in the United States. Contrast that, by the way, to the [623] people who have died globally, as of [May 17, 2003, as we go to press], due to SARS," he added. "If you factor in indirect costs such as the societal and microeconomic costs, there’s one estimate in the literature that ranges as high as $30 billion annually attributable to infections with resistant organisms in the United States."

While VRSA and MRSA are stealing the headlines, Fishman is more concerned about the stealth progress being made by resistant gram-negative pathogens.

"The reason I’m more concerned is because of the very few new antibiotics that are in development, none is being developed to address the problem of gram-negative resistance," he said. "Zero."

Yet gram-negative pathogens such as Pseudo-monas are becoming resistant to fluoroquinolones. At his own hospital, Fishman reports that a 6% Pseudomonas resistance level in 2000 has nearly tripled to 16% last year. "That’s a big concern, because it means we’re left without a drug to treat simple urinary tract infections," he said. "[There] is a strong correlation with fluoroquinolone use. So we’re even running out of drugs to treat our most common infections, not just less common hospital-based infections."

The various social, agricultural, economic, and medical pressures are coming together in a "perfect storm" scenario for the emergence of further antibiotic resistance, he warned.

"I’d like to be able to guarantee that my kids will have antibiotics when they need them, and standing here right now, I’m just not certain that they will," he said.