Proposals Seek to Reduce Resistance, Boost Development of New Antibiotics

Like many people who remember what life was like before antibiotics became widely available more than 50 years ago, Rep Phil Gingrey (R, Ga) appreciates the kinds of miracles the drugs deliver. When he was a child, his older brother developed pneumonia, and as Gingrey recalls, his parents were certain that the illness was the “kiss of death.” But the physician who came to their home to care for Gingrey's brother had a new drug to offer—an antibiotic.

Gingrey’s brother recovered.

Antibiotics still often offer remarkable cures for infections, but the spread of antibiotic-resistant bacteria strains, coupled with an anemic development pipeline for new antibiotics, are a threat, according to experts from the Infectious Diseases Society of America (IDSA), the US Food and Drug Administration, the US Centers for Disease Control and Prevention, the pharmaceutical industry, and congressmen who met in Washington in April at a gathering hosted by the IDSA. At the event, the society, Gingrey, and Rep Jim Matheson (D, Utah) presented proposals to combat the twin threats of resistance and the slow development of new antibiotics.

“We must take action now,” said FDA Commissioner Margaret A. Hamburg, MD. “The sad irony is we are facing a situation where tried-and-true drugs are losing value at the same time the pipeline of new drugs is devoid of new, innovative antibiotic drug candidates.”

Pharmaceutical companies are aware of the need for new antibiotics, said Paul Miller, PhD, vice president and chief scientific officer of Pfizer Inc's antibiotic research unit. But a number of factors have discouraged them from pursuing the development of such drugs. For example, he said, drugs for chronic conditions are likely to be more profitable than antibiotics, and physicians appropriately turn first to older, often generic antibiotics and reserve new ones to use as a last resort. Such factors mean that it may take longer for a company to recoup its investment for developing a new antibiotic compared with drugs for chronic conditions, which may achieve widespread use more quickly and provide a return on investment in just 3 to 5 years, he said. Additionally, because many antibiotics have been around for a long time, there is also an expectation that antibiotics will be inexpensive, he said.

Regulatory challenges also may have deterred companies from developing antibiotics, said Hamburg. More effective and efficient ways of assessing antibiotic safety and effectiveness are needed, she noted.

“How can we shape studies to give us the answers we need and be doable in a reasonable period of time and at a reasonable cost?” she said.

New legislation that is modeled after the Orphan Drug Act and intended to promote such regulatory changes and create incentives for companies to pursue new antibiotics is currently before Congress: the Generating Antibiotic Incentives Now (GAIN) Act. The bill, sponsored by Gingrey, would provide companies with an extra 5 years of patent protection and help to streamline the process for approval. The bill would also promote the development of rapid tests for bacterial infection and antimicrobial resistance, which are needed to improve both the use of existing antibiotics and facilitate research on drug candidates.

Another bill before Congress, the Strategies to Address Antimicrobial Resistance (STAAR) Act, introduced by Matheson, would reauthorize a federal antimicrobial task force and establish an office within the US Department of Health and Human Services to work on resistance. The bill would also create a national research plan and a surveillance and research network devoted to studying resistance and how to combat it, facilitate the collection of data to improve the surveillance of resistance, and support demonstration projects to boost appropriate use of antibiotics.

In a policy statement (http://cid.oxfordjournals.org/content/52/suppl_5/S397.full.pdf) released during the event, the IDSA offered support for both the GAIN Act and the STAAR Act, and for a third bill that would limit the agricultural use of medically important antibiotics. The policy statement also offered recommendations detailing how public and private organizations can work together to combat resistance and promote the development of new drugs.

“We are dealing with rampant antibiotic resistance throughout the United States and the world, but we don't have an effective federal effort,” explained Brad Spellberg, MD, assistant professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles, who helped develop the policy statement. To help fund the coordinated effort described in the statement, the IDSA supports the establishment of an Antibiotic Innovation and Conservation fee that would be added to the wholesale price of antibiotics; 75% of the proceeds would be used to fund new antibiotic development and 25% would be allocated for antibiotic stewardship programs.

“The time for action is now,” Spellberg said.