A new draft guidance document issued by the US Food and Drug Administration (FDA) is intended to provide clearer expectations for developers of therapies to treat hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP).

The guidance, Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Developing Drugs for Treatment, replaces an earlier 2010 guidance by the same name in the hopes of providing additional and updated details about appropriate clinical endpoints, enrollment criteria and noninferiority margin justifications.

For example, FDA explains in the guidance it is primarily interested a drug showing superiority relative to a control drug, though noninferiority trials may also be acceptable as evidence of effectiveness. A single, well-controlled trial might be sufficient to provide evidence of effectiveness, FDA indicated, but the trial parameters should be discussed with FDA prior to the trial being initiated.

FDA also recommends that companies should assemble a preapproval safety database involving, at a minimum, 500 patients.

The guidance also devotes significant attention to endpoints. FDA explained that sponsors should select one of two potential primary endpoints:

• A primary endpoint based on survival: all-cause mortality can be evaluated at a fixed time point at any time between day 14 and day 28.
• A primary endpoint based on survival and no disease-related complications: all-cause mortality or disease-related complications (e.g., development of empyema; onset of acute respiratory distress syndrome; other complications) can be evaluated at a fixed time point at any time between day 14 and day 28. Sponsors should discuss with the FDA the disease-related complications in advance of trial initiation.

As BioCenturyexplains, the guidance leaves out a primary endpoint of clinical response that was recommended in 2011 by an advisory committee, but retains it as a secondary endpoint.

As with two earlier guidance documents on antibiotic development, FDA also said it would allow the enrollment of patients even if they had been previously treated with antibiotics. However, patients who have received treatment with an antibiotic within the past 24 hours will not be allowed to enroll.

Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Developing Drugs for Treatment (FR)