Opinion

Novel Antibiotics Need a Dose of Incentives

On September 18, 2014, the U.S. waged war on bacteria.

The White House released a National Strategy for Combating Antibiotic Resistant Bacteria, which includes appointing a task force that will address a new report’s recommendations. The release coincided with President Obama signing an Executive Order allowing government agencies to combat the rise of such bacteria.

The White House also released a report from the Presidential Council of Advisors on Science & Technology (PCAST), a panel that analyzed the antibiotic issue for many months.

With the West African Ebola crisis taking center stage, antibiotic stakeholders were pleased to see action on another pressing public health matter.

Antibiotic resistant infections now cause at least 23,000 deaths annually in the U.S. Not only that, but they cause an estimated 2 million illnesses and add $20 billion to health costs each year. Another $35 billion is lost annually in productivity from hospitalizations and sick days due to these infections.

So what does the Obama Administration plan to do about it, and will it be enough? While it is a step in the right direction, additional regulatory & reimbursement incentives ought to be enacted quickly to get manufacturers to quickly step into the space and innovate.

Executive Order

The President views detecting, preventing, and controlling antibiotic resistance as a strategic, coordinated and sustained effort that involves the engagement of governments, academia, industry, healthcare providers, the general public, the agriculture community as well as international partners.

“The Federal Government will work domestically and internationally to detect, prevent, and control illness and death related to antibiotic resistant infections by implementing measures that reduce the emergence and spread of antibiotic resistant bacteria and help ensure the continued availability of effective therapeutics for the treatment of bacterial infections,” according to the Order.

The White House Executive Order can be found here.

The White House also announced that the Department of Health and Human Services will award up to $20 M for a rapid point of care diagnostic test to identify antibiotic resistant bacteria immediately.

Other highlights of Obama’s Executive Order include:

  • Directives to improve the current use of antibiotics to stem the spread of resistance bacteria;
  • Increase national surveillance efforts on the spread of such bacteria;
  • The promotion of new kinds of antibiotics; and
  • Strengthening international cooperation on the issue.

A task force will be created with new action plan deadline of Feb 15, 2015. The group will be dedicated to the problem and will be headed by the Secretaries of Defense, Agriculture, and Health and Human Services, as well as a presidential advisory council made up of top, non-governmental experts on the issue.

White House Scientific Advisors Report

A PCAST report released (found here) in tandem with the Executive Order also focused on the superbug conundrum.

What is PCAST? A group of health, technology and innovation experts that participate in public meetings to discuss pressing issues. include Google’s Eric Schmidt, Zetta Venture Partners’ Mark Gorenberg, former Nuclear Regulatory Commission Chair Shirley Ann Jackson, as well as other leading academics and health quality experts.

PCAST endorsed the so-called the Limited Population Antibacterial Drug (LPAD) pathway, which would expedite novel antibiotic approval by the FDA (ADAPT Act).

Under the LPAD mechanism, a drug’s safety and effectiveness would be studied in smaller, more rapid, and less expensive clinical trials—much like the Orphan Drug Program permits for other rare diseases. The ADAPT Act (Antibiotic Development to Advance Patient Treatment Act of 2013, or H.R. 3742) would create an official LPAD pathway, one that various Food and Drug Administration (FDA) officials have endorsed.

The main conclusions in the White House PCAST Antibiotics report can be found below:

  • Recommendation 1: Ensure Strong Federal Leadership. Intra-agency federal taskforce should be appointed by the President.
  • Recommendation 2: Effective Surveillance & Response for Antibiotic Resistance. (1) Strengthen State and local public health infrastructure for surveillance and response and (2) Establish a national capability for pathogen surveillance based on genome analysis.
  • Recommendation 3: Fundamental Research. (1) Expand fundamental research relevant to developing new antibiotics and alternatives for treating bacterial infections and (2) Develop alternatives to antibiotics in agriculture.
  • Recommendation 4: Clinical Trials with New Antibiotics. (1) Establish a robust national infrastructure to support clinical trials with new antibiotics and (2) Develop new regulatory pathways to evaluate urgently needed antibiotics.
  • Recommendation 5: The federal government should significantly increase economic incentives for developing urgently needed antibiotics.
  • Recommendation 6: Improving Stewardship of Existing Antibiotics in Health Care. (1) Centers for Medicare and Medicaid Services (CMS) should use reimbursement incentives to drive antibiotic stewardship (2) The Federal Government should use funding requirements to drive antibiotic stewardship (3) The Federal Government should lead by example in antibiotic stewardship in its own health care facilities and (4) Prizes for the development of breakthrough diagnostics.
  • Recommendation 7: Limit the Use of Antibiotics in Animal Agriculture.
  • Recommendation 8: Ensure Effective International Coordination.
Reimbursement

Some would argue that the regulatory environment for novel antibiotics is already quite attractive. That is, the FDA recognizes the need for novel agents and provides a fast track to final approval.

Reimbursement really is the key: most antibiotics are generic and therefore manufacturers do not have a financial incentive to pour research and development dollars into finding new agents to combat superbugs.

While the PCAST report endorsed enhanced antibiotic reimbursement via the Medicare program, the language was a bit vague.

A bill introduced in Congress, the DISARM Act (Developing an Innovative Strategy for Antimicrobial Resistant Microorganism, or H.R. 4187), would address part of the reimbursement quandary. With a growing co-sponsor list, the bill would enhance Medicare reimbursement for novel antimicrobial products (especially those targeting multidrug-resistant bacteria) in the hospital inpatient setting.

21st Century Cures

Following up on the White House’s strategy for combating antibiotic resistance, a House subcommittee on “21st Century Cures” discussed ways to encourage pharmaceutical companies to develop new antibiotics.

The ADAPT Act, from Reps. Gingrey (GA) and Green (D-TX), would make it easier for new antibiotics to win approval for use in small, high-risk populations.

Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, testified that “the current situation shows that the incentives are not enough.” However, she said, the challenge would be how to prevent physicians from prescribing the new drugs outside the very narrow groups for which they are intended.

The main topic of questioning at the hearing was about the need for financial incentives to generate medical innovation. Several roundtable participants and members of Congress discussed the need for rewards, such as the Infectious Disease Society of America (IDSA), Reps. Waxman (D-CA), Pallone (D-NJ), Gingrey (R-GA) and Shimkus (R-IL).

With the Congressional 21st Century Cures Initiative under way we could easily see ADAPT and possibly DISARM included in legislation (2015-16) to spur antibiotic innovation and swift regulatory passage/reimbursement for novel agents.

We would hope for speedier government action, as the issue appears to be non-controversial and bipartisan, and encourage Congress and the White House to make their recommendations a reality.