Panel okays new agent for C. difficile diarrhea.
SILVER SPRING, MD.--A Food and Drug Administration advisory panel voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium clostridium
Any of the rod-shaped, usually gram-positive bacteria (see gram stain) that make up the genus Clostridium. They are found in soil, water, and the intestinal tracts of humans and other animals. Some species grow only in the complete absence of oxygen. difficile-associated diarrhea in adults, based on clinical trial results.
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 in more than 1,000 patients were rigorous and well done and that rates of leukopenia leukopenia /leu·ko·pe·nia/ (-pe´ne-ah) reduction of the number of leukocytes in the blood below about 5000 per cubic mm.leukope´nic
basophilic leukopenia basophilopenia. , neutropenia Neutropenia Definition
Neutropenia is an abnormally low level of neutrophils in the blood. Neutrophils are white blood cells (WBCs) produced in the bone marrow that ingest bacteria. , 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.
Like other panelists, Dr. Christina Surawicz, professor of medicine at the University of Washington, Seattle, agreed that the two studies were well done. "And results were very positive. I have no reservations," she said.
The panel did not vote specifically on whether to recommend approval.
Fidaxomicin has a narrow spectrum of activity with bactericidal bactericidal /bac·te·ri·ci·dal/ (bak-ter?i-si´d'l) destructive to bacteria.
An agent that destroys bacteria (e.g. activity against C. difficile, and is poorly absorbed and locally active in the GI 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 CDI compact disc interactive: a system for storing a mix of software, data, audio, and compressed video for interactive use under processor control ), 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 diagnosed with mild to severe C. difficile--associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days (the proposed dosing regimen) was 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.) One of the studies was published in February (N. Engl. J. Med. 2011;364:422-31).
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).
A secondary end point, the "global cure" rate (defined as cure at the end of treatment plus no recurrence during 30 days of follow-up), favored fidaxomicin in the two studies, at 74% and 77%, compared with 64% and 63%, respectively, among those on vancomycin, a significant difference.
The rates of adverse events, serious adverse events, and deaths in the two groups were comparable. The rate of leukopenia (1.4% vs. 0.7%) and neutropenia (0.9% vs. 0%) were higher among those on fidaxomicin; most resolved without sequelae sequelae Clinical medicine The consequences of a particular condition or therapeutic intervention and more patients who developed leukopenias had predisposing conditions, such as lupus, or had had a bone marrow transplant bone marrow transplant: see bone marrow. , according to the company.
How the recurrence data will be communicated in the drug label and whether the indication will include the claim that treatment reduces recurrence is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.
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 poten tial 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.
BY ELIZABETH MECHCATIE
FROM THE FDA'S ANTI-INFECTIVE DRUGS ADVISORY COMMITTEE