ADAPT Act Would Create a New Limited Population Approval Pathway for Antibiotics and Antifungals

By Kurt R. Karst –    

On December 12th, a group of bipartisan lawmakers led by Representatives Phil Gingrey (R-GA) and Gene Green (D-TX) introduced H.R. 3742, the Antibiotic Development to Advance Patient Treatment Act of 2013 (“ADAPT Act”).  If enacted, the ADAPT Act would, among other things, amend the law to create a pathway for the prompt approval of antibacterial and antifungal drugs intended to treat serious or life-threatening diseases or conditions.  Introduction of the ADAPT Act came on the same day that FDA’s Dr. Janet Woodcock testified during a House hearing concerning drug development and manufacturing challenges that legislation is needed for FDA to create a program to develop products designed to attack drug-resistant “superbugs” (see here).  In addition, earlier this week, FDA issued a proposed rule and guidance document concerning the use of antimicrobial new animal drugs to assure their appropriate and judicious use.  There has been growing concern about the risk of antimicrobial resistance from the use of drugs in food-producing animals, and at least one bill is pending in Congress: S.1256, the Preventing Antibiotic Resistance Act of 2013.

The ADAPT Act has been in the works for some time now.  The approval mechanism it would create has been informally known as the Limited Population Antibacterial Drug (“LPAD”) pathway, and has drawn strong support from the Pew Charitable Trusts and the Infectious Diseases Society of America (see here and here).  Earlier this year, FDA held a public hearing on “Creating an Alternative Approval Pathway for Certain Drugs Intended to Address Unmet Medical Need” (Docket No. FDA-2012-N-1248) at which both organizations called for the creation of the LPAD pathway. 

The ADAPT Act is viewed as successor legislation to the Generating Antibiotics Incentives Now Act (‘GAIN Act”), which was enacted in July 2012 as part of the FDA Safety and Innovation Act.  The GAIN Act, which itself builds on provisions included in 2007 FDA Amendments Act (“FDAAA”), is intended to improve antibiotic access and innovation by providing incentives for the development of qualified infectious disease products (see our summary here; pages 47-50). 

So what exactly does the ADAPT Act do to advance drug development?  According to a press release from Rep. Gingrey, the ADAPT Act advances drug development in three ways:

1.)    Develops a new, accelerated pathway for antibiotics and antifungals

This pathway provides for FDA-approval of drugs in order to treat emerging threats in limited and specific patient populations.

2.)    Strengthen resistance monitoring by the CDC

The CDC will also monitor use of antibiotics to treat serious and life-threatening infections and make this data publically available to providers, hospitals, and academics.

3.)    Update Susceptibility Test Interpretive Criteria for Microbial Organisms or “breakpoints”

The ADAPT Act streamlines the antibiotics labeling process at the FDA to ensure up-to-date and cutting-edge data is available to healthcare professionals.

Specifically, the ADAPT Act would amend the FDC Act to add Section 505(x), allowing the sponsor of an antibacterial or antifungal drug intended to treat a serious or life-threatening disease or condition (or a biological products intended to treat a bacterial or fungal infection associated with a serious or life-threatening disease) to request that FDA approve the drug “to treat a limited population of patients for which there is an unmet medical need.”  In determining whether to grant such approval for a limited population of patients, FDA “may rely on traditional endpoints, alternative endpoints, or a combination of traditional and alternative endpoints; datasets of limited size; pharmacologic or pathophysiologic data; data from phase 2 clinical studies; and such other confirmatory evidence as the [Agency] deems necessary.”  The labeling of products approved under the limited population pathway must include the statement: “This drug is indicated for use in a limited and specific population of patients.”

The bill would also ament the Public Health Service Act (“PHS Act”) to require FDA to use the National Healthcare Safety Network (or another appropriate monitoring system) to monitor the use of antibacterial and antifungal drugs (including limited population drugs under proposed FDC Act § 505(x)), and to monitor changes in bacterial and fungal resistance to drugs.  Data collected by FDA under such monitoring would be made public for the purposes of “improving the monitoring of important trends in antibacterial and antifungal resistance,” and “ensuring appropriate stewardship of antibacterial and antifungal drugs.”  This portion of the ADAPT Act somewhat resembles provisions in H.R. 2285, the Strategies to Address Antimicrobial Resistance Act, which was introduced earlier thie year.

Finally, the ADAPT Act would amend FDC Act § 511, which was added to the statute by the 2007 FDAAA, to require FDA to “identify upon approval and subsequently update susceptibility test interpretive criteria for antibacterial drugs (including biological products intended to treat a bacterial infection and other types of antimicrobial drugs, as deemed appropriate by [FDA]), including qualified infectious disease products.”  Susceptibility test interpretive criteria, which are more commonly known as “breakpoints,” are used to select an appropriate antibacterial drug to treat a patient with a bacterial infection.  A “breakpoint” reflects the concentrations at which bacteria are categorized as susceptible to treatment with a given antibiotic drug and can change over time.  An outdated breakpoint can result in the unknowing selection of ineffective treatments, which can also contribute to antibiotic resistance.  As we previously reported, the Government Accountability Office issued a report in January 2012 saying that FDA has not taken sufficient steps to ensure that antibiotic labels contain up-to-date information.  In October 2013, FDA held an advisory committee meeting to discuss breakpoints.

Immediately after introduction of the ADAPT Act, the Pew Charitable Trusts applauded the action in a letter to Representatives Gingrey and Green.  “Your legislation would help streamline the regulatory pathway for antibiotics that could address [carbapenem-resistant Enterobacteriaceae] and other dangerous pathogens,” wrote the organization.  “Drugs approved under this pathway would be studied for use in smaller populations than other antibiotics.  This will help lower development costs and make clinical trials more feasible.”