FDA releases draft guidance to spur development of CDI drugs

New guidance released by FDA provides advice for sponsors on developing drugs for treating Clostridioides difficile infection (CDI). The draft guidance discusses how to design trials and trial populations, efficacy and safety endpoints, nonclinical studies, and pharmacokinetic studies.

CDC described C. difficile as “threat-level urgent” in its 2019 Antimicrobial Threats Report and estimates that C. difficile causes the hospitalizations of 223,900 individuals per year and 12,800 annual deaths.

The guidance examines the development of CDI treatments consisting of small molecule drugs and biological products and how to reduce the recurrence of CDI, especially in at-risk patients.

Clinical trials should be randomized, double-blinded, and use an active control for both CDI treatment and curbing CDI recurrence, FDA’s guidance document said.

To demonstrate efficacy, sponsors should supply evidence from 2 competent and well-controlled trials, with one trial demonstrating efficacy only for treatment and another trial for preventing CDI. Sponsors are advised to submit safety data from at least 300 individuals exposed to the proposed investigational drug treatment. Clinical programs for drugs developed only for preventing CDI may require a larger safety database.

Sponsors should discuss a suitable size of the premarket safety database with FDA during clinical development. For nonclinical studies, applicants should test the investigational drug in vitro and in animal models prior to submitting an investigational new drug application.

FDA also recommends an I.V. toxicology study in at least one mammalian species to identify possible risks, noting that CDI may increase oral drug absorption because of the disruption of the intestinal barrier.