FDA Finalizes Guidance on Antibacterial Therapies for Unmet Needs

The US Food and Drug Administration (FDA) on Tuesday finalized guidance first drafted in 2013 to assist sponsors in the development of new antibacterial drugs for the treatment of serious bacterial diseases in patients with an unmet medical need.

"After consideration of comments received in response to the draft guidance, FDA updated the guidance to include clarifications about trial designs for streamlined development programs and statistical approaches," the agency said in Tuesday's Federal Register notice. "In addition, the guidance outlines development approaches for antibacterial drugs that are pathogen-focused (i.e., drugs that are intended to treat a single species or a few species of bacteria) and, accordingly, fulfills the requirements of section 806(a), Title VIII (entitled ‘Generating Antibiotic Incentives Now') of the Food and Drug Administration Safety and Innovation Act."

The agency also notes that some antibacterial drugs that are candidates for streamlined development may also be candidates for a limited population pathway for certain antibacterial and antifungal drugs (LPAD) established in section 3042 of the 21st Century Cures Act.

"FDA intends to issue separate guidance regarding LPAD. Sponsors are encouraged to discuss proposed approaches with the Division of Anti-Infective Products," the guidance says.

Background

While noting that efforts to develop new antibacterial drugs have diminished in the past few decades, the agency also cautions that "bacteria continue to develop resistance to available antibacterial drugs," and situations have occurred in which patients with serious bacterial diseases have limited or in some cases no alternative antibacterial drugs available for treatment.

"To foster new antibacterial drug development that will have the potential to keep pace with continued selective pressures of antibacterial resistance, FDA is exploring approaches to help streamline development programs for new antibacterial drugs. This guidance outlines approaches for streamlined development programs that are consistent with FDA's longstanding commitment to regulatory flexibility regarding the evidence required to support drug approval for patient populations with serious disease and limited or no treatment options, while meeting appropriate standards for safety and effectiveness," FDA says.

Guidance

In the form of 17 questions and answers, the guidance offers perspective on a variety of topics related to streamlined drug development.

At the outset, FDA reveals which types of antibacterial drugs are likely to be appropriate for a streamlined development, including those with: "(1) a new mechanism of action that preserves antibacterial activity against bacteria that have mechanisms of resistance to other available antibacterial drugs; (2) an added inhibitor that neutralizes a mechanism of resistance; (3) an alteration in the structure of the molecule that makes the drug no longer susceptible to the mechanisms of resistance to existing drugs; or (4) some other characteristic that has a potential to lead to enhanced effectiveness. A drug that has slightly greater potency (e.g., more active by 2- to 3-fold dilutions based on in vitro testing) generally would not be considered a drug that addresses an unmet need and should undergo a traditional development program."

In terms of clinical trials and non-clinical considerations, FDA explains what should be provided and says: "To the extent that a streamlined clinical development program involves smaller, shorter, or fewer clinical trials, it is likely that less safety data will be generated, and the nonclinical studies may assume an even more important role in contributing to the evaluation of the safety of an antibacterial drug. Thus, the nonclinical evaluations should not be smaller or streamlined."

The agency also discusses which kinds of adaptive trial designs can be considered, as well as noting that a safety database for a drug that is the subject of a streamlined development program should include about 300 patients at the dose and duration of therapy proposed for marketing.

And FDA also defends itself against the argument that a streamlined development program for antibacterial drugs may result in a lower regulatory standard for drug approval.

Antibacterial Therapies for Patients With an Unmet Medical Need for the Treatment of Serious Bacterial Diseases: Guidance for Industry