A new draft guidance document issued by US regulators looks to expedite and facilitate the clinical development of drug therapies intended to treat community-acquired bacterial pneumonia (CABP).
FDA had last issued a guidance on CABP in 2009, but said feedback prompted it to make significant changes to "attain a greater degree of balance between the practicability of conducting CABP clinical trials and the trial procedures needed for a scientifically sound and interpretable trial."
Similar problems have long presented an issue for sponsors of antimicrobial products. Under normal circumstances, FDA wants a trial to only enroll patients who have not recently received any other treatments. However, while this is feasible for many conditions, it is rare that a patient with an infection would not have received antibiotics or other interventions.
A similar problem was noted in FDA's recent Antibacterial Therapies for Patients with Unmet Medical Need for the Treatment of Serious Bacterial Diseasesguidance, in which the agency conceded that while not ideal, trials could still enroll non-treatment-naïve individuals.
FDA's Community-Acquired Bacterial Pneumonia: Developing Drugs for Treatmentdraft guidance is conceptually similar to the Antibacterial Therapies in many respects-not surprising given that pneumonia is itself a fairly serious infection in many cases.
The draft guidance calls for any drug to be studied to be effective against the "commonly implicated pathogens" which cause CABP, and be studied in those who "most likely have CABP" and would thus stand to benefit from treatment.
Unlike the Antibacterial Therapies guidance, however, FDA states that superiority trials and noninferiority trials will be acceptable. The Antibacterial Therapies guidance had placed a heavy emphasis on superiority trials, much to the chagrin of industry.
Explains FDA: "A single adequate and well-controlled trial in CABP supported by evidence of antibacterial activity accrued during a clinical development program (e.g., efficacy in another indication such as acute bacterial skin and skin structure infection; data from a phase 2 clinical trial in CABP) may provide evidence of effectiveness in CABP. Sponsors should discuss their proposed CABP development program with the FDA as well as the other independent evidence that would be used to support the findings from a single trial."
The guidance calls for a primary efficacy endpoint of improvement between three and five days after the start of treatment (per symptoms defined in the guidance) based on a four-point scale of absent, mild, moderate and severe. Another endpoint is all-cause mortality at day 28, but FDA said sponsors should discuss the use of this endpoint with FDA prior to use.
Comments are due by 10 April 2014.
Community-Acquired Bacterial Pneumonia: Developing Drugs for Treatment