Bad bugs, no drugs

October 2004

The headline above, as all Infectious Diseases Society of America (IDSA) members should know by now, is the title both of a monograph describing the brewing public health crisis and of a multi-year effort to bring this matter to the attention of the public and its elected leaders. It was publicly announced in July 2004 and may already be having some impact. It would be difficult to overestimate the importance of this public policy initiative — probably the most critically important ever undertaken by the IDSA.

This undertaking is in some ways the culmination of a multiyear effort by the Society’s Task Force on Antimicrobial Availability. The chair of the group has been Dr. John Bartlett, and members have included Drs. John Bradley, John Edwards, Dave Gilbert, Mike Scheld and George Talbot. Important advisors have been Drs. John Powers, David Shlaes and Frank Tally. They all deserve the gratitude and the strong support of all of us for their efforts.

There is, of course, a substantial background of scientific literature in the last several years that attests to the increasing problems of multidrug resistance and the gradual steady decline in new antibiotic development. The Institute of Medicine has been concerned about these issues as well, and the publication in 2003 of the report “Microbial Threats to Health: Emergence, Detection, and Response” placed the substantial scientific respect of the IOM on the need for some legislative and regulatory response.

The IDSA’s task force evidently planned to focus these issues as clearly as possible in the scientific literature before initiating this program, and so there appeared a series of publications to accomplish that goal; many of you have probably read or at least seen them.

They include (1) “Trends in antimicrobial drug development: implications for the future” by Brad Spellberg, John Powers, Eric Brass, Loren Miller and John Edwards (Clin Infect Dis. 2004;38:1279-1286); (2) “Antibiotic discovery: state of the state” by David Shlaes, Steven Projan and John Edwards; and (3) “Why it is important to continue antibacterial drug discovery” by Karen Bush. The latter two reports were both published in the June 2004 issue of ASM News.

With those and other reports documenting the scientific background, the stage was set to examine the issues and consider possible solutions. In preparing its recommendations, the Task Force met during its deliberations with a large number of stakeholders, including government (the National Institute of Allergy and Infectious Diseases, the FDA, the CDC, and congressional members and staff), pharmaceutical and other product development industry leadership and the public. These are all contained in the brochure “Bad Bugs, No Drugs,” which is primarily aimed at societal, governmental and industry leadership. This is a well-planned document, and well worth the brief amount of time required to read it.

The existing problems in multi-drug resistance and the reasons therefor, as well as the problems and incentives for new antibiotic development are delineated, as well as a series of both legislative and regulatory “fixes.” Interspersed are a number of examples of both epidemic and individual patient problems from real life, including an outbreak of multidrug-resistant salmonellosis and several devastating community-acquired methicillin-resistant Staphylococcus aureus infections.

The solutions proposed are in three parts: those directed to Congress, those directed to NIAID and those directed to the FDA. These will be summarized briefly for those who are not already familiar with them:

Potential legislative remedies to foster innovation

• Establish and empower an independent commission to prioritize and incentivize antimicrobial discovery efforts.
• Establish further intellectual property protections, eg, by extending market exclusivity rights, restoring patent time lost during the FDA review process, or giving innovative new antibiotics for multidrug-resistant organisms “orphan drug” status.
• Consider other potential statutory incentives, such as tax incentives for research and development of priority antibiotics, measured liability protection, giving more flexibility to FDA regarding antibiotic approval, antitrust exemptions and even a market guarantee.
• Establish similar incentives to spur research and development for rapid diagnostic methods for targeted pathogens.
• Consider statutory incentives to foster start-up and small biopharmaceutical development companies.

Recommendations for NIAID

• Aggressively encourage translational research.
• Remove roadblocks to antibiotic research and development, including unnecessary restrictions on companies’ intellectual property rights.
• Increase priority drug development through grant programs.
• Develop and expand collaborations with industry and the ID community.
• Launch a new study section supporting the drug discovery and antimicrobial resistance program.
• Explore with FDA all opportunities to streamline new antibiotic development.

There are several others as well, but the above are sufficient to understand the thrust of these recommendations.

Recommendations for FDA

• Provide updated guidelines for antibiotic clinical trials and encourage innovative clinical trial designs.
• Provide a clear definition of acceptable surrogate markers as end points in clinical trials of priority antibiotics.
• Explore use of animal models in antibiotic efficacy studies to reduce the number of human efficacy trials required.
• Grant priority antibiotics accelerated review status.

Finally, to support all these recommendations, it is clear that substantial additional funding will be necessary for CDC’s antimicrobial resistance program and for NIAID and FDA.

It should be abundantly clear, of course, that this must be a multiyear effort, and that the publication of one brochure, no matter how well done, will not bring about the needed changes in public policy. We are assured by the IDSA leadership that this effort will be ongoing for as long as it takes. We wish them well! In the September newsletter, IDSA President Joe Dalovisio indicated that progress is already being made and that congressional hearings on drug development against bioterrorism and drug-resistant pathogens will be held later this fall.