A New Way to Approve Antibiotics for Drug-Resistant Infections

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A New Way to Approve Antibiotics for Drug-Resistant Infections

An approval pathway for limited-population antibacterial drugs (LPAD) would help advance the development of new antibiotics for seriously ill patients with unmet medical needs.

Q: What would LPAD do?

A: The LPAD pathway would provide a unique mechanism for the Food and Drug Administration to review and approve new antibacterial drugs that address unmet medical needs for specific, limited populations of patients—those with serious and life-threatening bacterial infections that are resistant to current treatments.

This targeted approach would make antibiotic development more feasible by allowing for smaller clinical development programs that are focused on the limited, high-risk populations that would use these new antibiotics, instead of on more general populations that can be treated with existing medicines. LPAD would also make antibiotic development more feasible by enabling FDA to assess these drugs based on the unique balance of benefits they offer vs. risks they present to the limited number of patients they are intended to treat—specifically, patients who have few or no other treatment options.

Q: What types of medicines would qualify for LPAD review?

A: Only medicines intended to treat serious and life-threatening bacterial infections in patients who have unmet medical needs—meaning they have few or no viable treatment options—would qualify for review and approval via the LPAD pathway.

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LPAD would help advance the development of new antibiotics for seriously ill patients with unmet medical needs.

Q: Why is an LPAD pathway needed?

A: Doctors and patients are running out of options to effectively treat drug-resistant infections1, and there are not enough new antibiotics in development to meet growing patient needs.

The majority of infectious disease doctors report having treated patients with infections that did not respond to any antibiotics.2 At the same time, there has been a nearly 30-year void in the discovery of new types of antibiotics critical to addressing resistance.

By making the development of high-need antibiotics more feasible, the LPAD pathway will help spur innovation and investment to reinvigorate the pipeline, and ultimately bring new medicines to patients who have run out of options.

Q: What patients would be most likely to benefit from LPAD?

A: Patients who contract multidrug-resistant infections that do not respond to existing antibiotics would benefit from drugs approved through an LPAD pathway. Many such infections are contracted in hospitals or health care settings, but they can also be acquired in community settings such as day care facilities and gyms, as part of everyday activities.

Q: What is the difference between LPAD approval and Accelerated Approval?

A: There are several key differences between LPAD and FDA’s existing Accelerated Approval program.

  • LPAD approvals would be full and final approvals, not contingent on additional follow-up studies the way Accelerated Approvals are. LPAD is not an expedited development program.
  • Unlike Accelerated Approval, or any of FDA’s other existing expedited programs, LPAD offers approvals limited to specific populations of patients with unmet medical needs.
  • LPAD would be the only approval mechanism to utilize mandatory additional measures (outlined below) to help ensure that drugs approved through the pathway are used appropriately.

Q: Could medicines qualifying for LPAD review also qualify for additional FDA expedited review programs?

A: Yes. Drug candidates that qualify for LPAD review may simultaneously qualify for one or more of FDA’s expedited review programs. In fact, there is an expectation that medicines qualifying for LPAD review would be a subset of drugs designated as “qualified infectious disease products” under the Generating Antibiotics Incentives Now (GAIN) Act, a designation that makes drugs eligible for Fast Track and Priority Review designation.

Q: Does LPAD lower the safety and efficacy standard for FDA approval?

A: No. LPAD maintains the current standard for FDA approval. As with drugs approved under FDA’s traditional pathway, sponsors seeking approval of antibiotics via the LPAD pathway must demonstrate safety and provide “substantial evidence” of these drugs’ effectiveness. Substantial evidence is defined in Section 505(d) of the Federal Food, Drug, and Cosmetic Act as “evidence consisting of adequate and well-controlled investigations, including clinical investigations.”

Medicines approved under the LPAD pathway will need to demonstrate safety and effectiveness for the specific, limited population in which they are intended to be used, not for a more general population that could be treated with existing drugs. As such, LPAD would make it possible to meet the FDA’s standards using smaller clinical trials and enable the FDA to make risk-benefit assessments tailored to limited populations of patients most in need—those with potentially fatal infections and few or no remaining treatment options.

Q: Would LPAD allow for approvals based only on nonclinical data?

A: As is the case with all FDA-reviewed drugs, the agency would be able to consider a wide range of data when determining whether to approve a new antibiotic for use in a limited population, including both clinical and nonclinical data. This ability to draw on multiple types of data does not in any way change or negate FDA’s substantial evidence standard requirements, which explicitly call for clinical investigations.

Additionally, Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research, has clearly stated that clinical data, including human clinical trials, will be expected for any antibiotics approved under LPAD.

Q: How would regulators ensure that limited-population drugs would be used only in the target population?

A: LPAD has several safeguards to help ensure that these drugs are used appropriately and only in the approved population, including:

  • Prominent branding, so physicians and other caregivers understand that the drug has been demonstrated to be safe and effective only in limited populations.
  • Preapproval of marketing materials by FDA, to ensure that the drugs are marketed for use as intended in only the target population and not for any other purpose.
  • Postmarket surveillance to assess whether the limited population indication is working as intended or whether the drugs are being used in the broader population for whom they haven’t been evaluated.

Q: Why is LPAD needed in addition to the GAIN Act?

A: The two approaches are complementary. GAIN is a 2012 law that provides an economic incentive to drug companies that bring new antibiotics to market for serious or life-threatening infections. In contrast, LPAD helps streamline the development process for high-need antibiotics and makes it more feasible for drugmakers to test and receive approval for new antibiotics.

Q: Why would a drug company seek LPAD approval?

A: The LPAD pathway would provide a way for companies to focus on specific populations of patients with unmet needs when testing new therapies, making antibiotic development more feasible—scientifically and financially.

Q: Who supports the LPAD approach?

A: Support for the LPAD pathway is broad, bipartisan, and growing.

A wide variety of stakeholders across the public and private sectors have endorsed LPAD, including professional associations representing health care providers, hospitals, pharmacists, clinical laboratory scientists and medical microbiologists, public health experts, patients, and advocates.

Additionally, current and former FDA officials, the President’s Council of Advisors on Science and Technology, and the Bipartisan Policy Center are among the prominent leaders supporting and advocating for an LPAD pathway.  

Below is a list of organizations that have signed letters to the 114th Congress in support of legislation that would make LPAD a reality:

  • Alliance for Aging Research
  • Alliance for the Prudent Use of Antibiotics
  • American Academy of Allergy, Asthma & Immunology
  • American Academy of Pediatrics
  • American College of Preventive Medicine
  • American College of Rheumatology
  • American College of Surgeons
  • American Gastroenterological Association
  • American Pharmacists Association
  • American Public Health Association
  • American Society for Microbiology
  • American Society of Transplant Surgeons
  • American Thoracic Society
  • Antibiotics Working Group (Cempra, Durata Therapeutics, Optimer Pharmaceuticals, Melinta, The Medicines Co., and Theravance) 
  • Association for Professionals in Infection Control and Epidemiology
  • Association of State and Territorial Health Officials
  • Cempra Inc.
  • Center for a Livable Future
  • Dignity Health
  • Harm Reduction Coalition
  • Health Care Without Harm
  • HIV Medicine Association
  • Infectious Diseases Society of America
  • Making a Difference in Infectious Diseases
  • Microbion Corp.
  • National Association of County and City Health Officials
  • National Association of Pediatric Nurse Practitioners
  • National Coalition of STD Directors
  • National Foundation for Infectious Diseases
  • National Military and Veterans Alliance
  • National Tuberculosis Controllers Association
  • ONCORD Inc.
  • Pediatric Infectious Diseases Society
  • Society for Healthcare Epidemiology of America
  • Society of Critical Care Medicine
  • Society of Infectious Diseases Pharmacists
  • The Pew Charitable Trusts
  • Theravance Biopharma
  • Trust for America's Health
  • UPMC Center for Health Security

Endnotes

  1. Centers for Disease Control and Prevention, Antibiotic Resistance Threats to the United States, 2013, last modified July 17, 2014, http://www.cdc.gov/drugresistance/threat-report-2013/index.html.
  2. Adam L. Hersh et al., “Unmet Medical Need in Infectious Diseases,” Clinical Infectious Diseases (April 2, 2012), http://dx.doi.org/10.1093/cid/cis275.