The landscape for antibiotic drug development has been shaken in recent years by scientific, regulatory and political disputes over the appropriate balance between the desire for scientific certainty in clinical trials and the pragmatic need to increase the reservoir of treatments for increasingly resistant pathogens. Indeed, the Infectious Diseases Society of America (IDSA) has been warning for years that shifting regulatory goalposts and the lack of consistent guidance about approval requirements have created serious impediments to the development of much-needed new antibiotics.
The core question in setting approval standards for antibiotics is whether FDA should require that efficacy claims be rooted in placebo-controlled trials, and several late-stage development programs were crushed last year when FDA closed the door on the use of non-inferiority (NI) trials to support approvals of drugs for self-resolving bacterial infections (see "Moving the Goal Posts," A2).
FDA took an initial step toward mitigating the regulatory uncertainty on Oct. 12 when it released draft guidance on Antibacterial Drug Products: Use of Noninferiority Studies to Support Approval.
As expected, the guidance codifies what FDA has already said about drugs for self-resolving infections: they require either placebo-controlled or superiority trial designs (see BioCentury, Sept. 18, 2006).
What may not have been expected was the proposed guideline's call for sponsors who have conducted or plan to conduct an NI trial to re-evaluate the protocol, and to submit a revised IND with a scientific justification for the non-inferiority design "as soon as possible."
The draft also sweeps off the table any previous agreements for the use of NIs to test any antibacterial agents, including special protocol assessments and other less binding commitments to protocol designs. It states that because "the state of the science has changed, prior commitments from the FDA under an SPA may no longer be valid for some products."
The draft suggests that sponsors "submit a new protocol as part of an SPA, or request a new SPA for a previously reviewed SPA" (see Online Links, A29).