Q & A
'ADAPT': A Regulatory Pathway to Develop Antibiotics and Fight Drug Resistant Infections
For more information on approving new antibiotics for limited populations of patients, see this updated information.
On Dec. 12, 2013, a bipartisan bill was introduced in the U.S. House of Representatives to encourage development of antibiotics for patients with serious or life-threatening bacterial infections. The new legislation would direct the U.S. Food and Drug Administration, or FDA, to approve new antibiotics and antifungal drugs for specific, limited populations of patients who have infections for which few or no suitable options exist.
The Antibiotic Development to Advance Patient Treatment—or ADAPT Act (H.R. 3742)—was introduced by 10 members of the House Energy and Commerce Committee: Representatives Phil Gingrey (R-GA), Gene Green (D-TX), John Shimkus (R-IL), Anna Eshoo (D-CA), Ed Whitfield (R-KY), Diana DeGette (D-CO), Marsha Blackburn (R-TN), Eliot Engel (D-NY), Morgan Griffith (R-VA), and G.K. Butterfield (D-NC).
Why is an alternate regulatory pathway for limited-population antibacterial drugs needed?
Antibiotic resistance is on the rise. More than half of infectious disease doctors surveyed have cared for a patient with an infection resistant to all available antibiotics.1
The Centers for Disease Control and Prevention, or CDC, recently emphasized the risk of losing effective antibiotics—which would not only limit the ability to fight routine infections, but would also erode the ability to safely perform surgery, treat cancer and rheumatoid arthritis, and provide kidney dialysis and organ transplants.2
As FDA acknowledges, it is difficult to identify and enroll patients with highly resistant bacterial infections in sufficient numbers for traditional, large-scale clinical trials because of the small number of patients with these serious conditions. ADAPT's limited-population approval pathway should help make antibiotic development more feasible—scientifically and financially—by allowing for smaller clinical studies.
What would the ADAPT Act do?
ADAPT would direct FDA to approve new antibiotics and antifungal drugs that address unmet medical needs for specific, limited populations of patients. Antibiotics approved under this pathway would be intended for serious or life-threatening infections for which few or no suitable options currently exist, and would be studied for use in smaller populations than antibiotics used for broader indications or conditions.
To ensure that drugs approved under ADAPT are used only for the intended patients, these drugs would bear labels alerting health care providers to the limited population for whom they are indicated. ADAPT also would give FDA the authority to review promotional materials before a drug developer could use them for marketing, and would mandate evaluation of how antibiotics approved under this pathway were prescribed.
What types of studies would be required for the approval of antibiotics under this pathway?
ADAPT would give FDA the flexibility to consider a variety of evidence in determining whether to approve antibiotics for limited populations, but it would not mandate that particular data be submitted. In general, FDA regulations do not specify the level of evidence needed to support the approval of a drug. Rather the agency develops, publishes, and updates these standards in the form of guidance documents that assist drugmakers in planning clinical development programs for new antibiotics. The agency recently issued draft guidance on the development of antibacterial therapies for patients with unmet medical needs.
Is ADAPT an expedited pathway or accelerated approval?
While products developed under ADAPT would still be eligible for existing expedited FDA pathways (such as fast track, breakthrough therapy, accelerated approval, and priority review), ADAPT would not guarantee a shorter review time by the agency. Nor does ADAPT specify use of a “surrogate endpoint” as a proxy for a patient's clinical response as under the accelerated approval pathway described under 506(c) of the Federal Food, Drug, and Cosmetic Act. However, as previously noted, drugs approved under this pathway may take less time to develop because clinical studies would likely be smaller than those conducted for approval of broader indications.
Would the ADAPT Act lower the safety and efficacy standards needed for FDA approval?
ADAPT clearly specifies that drugs approved under the pathway would have to meet the same safety and efficacy standards as any other drug under existing law.
Every approved drug is meant to treat a specific population, and the benefit-risk calculation for patients who lack other treatment options is different from that of broader populations with easily treatable infections.
Under ADAPT, FDA would consider benefits and risks for the sickest patients with few or no available treatment options. The level of acceptable risk for these patients is different from those with readily available treatment options. The labeling and marketing provisions in ADAPT would help reduce the likelihood that the drug would be used indiscriminately in populations that could be adequately treated with a therapy approved for a broader population.
Why is the ADAPT Act needed in addition to the Generating Antibiotic Incentives Now, or GAIN, Act?
The two approaches are complementary. GAIN is a 2012 law that provides an economic incentive to drugmakers that bring new antibiotics for serious infections to market. In contrast, ADAPT helps streamline the regulatory process for antibiotics and make it more feasible for drugmakers to test antibiotics for the patients that need them most and to obtain FDA approval.
Is the ADAPT Act limited to antibiotics?
In addition to antibiotics, ADAPT also addresses antifungal drugs, both of which pose urgent and unique challenges that require special attention. While antibiotic resistance has increased, few new antibiotics have reached the market over the past decade, and there is currently an unmet medical need for new therapies to treat some serious infections—particularly those caused by resistant Gram-negative pathogens.
What ensures that ADAPT drugs would be used as intended?
ADAPT would not limit a physician's ability to choose the most appropriate drug, but the bill contains several important provisions that would reduce the likelihood that limited-population drugs would be used in broader populations. The designation as a limited-population drug and mandatory labeling would communicate to physicians and other health care providers that these antibiotics were demonstrated to be safe and effective only in limited populations.
ADAPT would also give FDA the authority to review promotional materials prior to distribution and require monitoring of the usage of antibiotics approved under this pathway.
In addition to the designation requirements already in the bill, Pew is advocating for labeling with prominent language or other visual elements making the approved use of these drugs immediately clear.
1 A.L. Hersh et al., “Unmet Medical Need in Infectious Diseases,” Clinical Infectious Diseases (April 2, 2012), doi:10.1093/cid/cis275.
2 Centers for Disease Control and Prevention, Antibiotic Resistance Threats to the United States, 2013, http://www.cdc.gov/drugresistance/threat-report-2013/index.html.