The FDA says a single, well-controlled trial may be used to support a drug candidate for treatment of pulmonary tuberculosis (TB) if additional confirmatory evidence is available, in a revised draft guidance released last week.

The 23-page document, which replaces a November 2013 draft, includes detailed recommendations for nonclinical models, early phase studies and trial design considerations, including how to demonstrate efficacy using superiority or noninferiority trial designs.

For demonstrating efficacy, the agency suggests that a “single adequate and well-controlled trial in subjects with pulmonary TB,” supported by other confirmatory evidence, such as evidence of antimycobacterial activity from nonclinical data or phase 2 trials, “may provide evidence of effectiveness when the single trial demonstrates a clinically meaningful and statistically robust treatment effect.”

The revised draft also includes additional information on the inclusion of children in studies, safety considerations and labeling. The draft does not deal with drug development for latent TB infection or for extrapulmonary TB.

The FDA noted that treatment of TB includes more than one drug in a treatment regimen and that sponsors may be developing more than one investigational drug as part of a new combination regimen, adding that they should consult with the FDA early during development of their plans to develop TB drugs as part of a combination regimen.

Sponsors should also assess potential drug-drug interactions that may occur during coadministration with other antimycobacterial drugs, such as antiretrovirals, because many TB patients have comorbidities and receive medications for those conditions.

The deadline for comment on the draft is Feb. 13, 2023.

Read the FDA draft guidance here: https://bit.ly/3huXSSD.