SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.
At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.
The panel did not vote specifically on whether to recommend approval of fidaxomicin.
Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."
In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)
The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.
In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.
The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.
The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.