Fidaxomicin Advisory Committee: FDA Wants Advice On The Meaningfulness Of Infection Recurrence

Approval of Optimer's antibiotic for C. difficile seems assured, but strength of label remains a question.

FDA accepts findings by Optimer Pharmaceuticals that the firm's Dificid (fidaxomicin) is superior to vancomycin in curing Clostridium difficile-associated diarrhea and preventing its return, but will ask an advisory panel April 5 whether the lower recurrence is clinically significant and should be discussed in labeling.

The company is seeking an indication for the first-in-class macrolide antibacterial for treating CDAD, or C. difficile infection, and for reducing the risk of recurrence when used for treatment of initial CDI.

Failure of the Anti-Infective Drugs Advisory Committee to support language about fidaxomicin's impact on recurrence could undercut Optimer's plans to position the antibiotic as first-line treatment for patients considered to be at-risk for recurrence (Also see "Emboldened By Strong Data, Optimer Licenses Antibiotic Candidate To Astellas" - Pink Sheet, 7 Feb, 2011.).

Currently, vancomycin and metronidazole are the most common therapies for C. difficile infection, although only the former is approved for that use. But about 20% to 30% of those who respond to the two drugs have a recurrence of the infection within two months post-therapy, Optimer pointed out when it outlined its vision for the drug.

Fidaxomicin has a better profile with regard to preventing recurrence, the firm says in briefing documents for the meeting. Based on two Phase III studies that looked at global cure - a composite of cure at end-of-treatment and no recurrence by the post-study visit - Optimer reported superiority for its drug.

In the modified intent-to-treat population, the global cure was 74.4% for fidaxomicin patients and 64.2% for vancomycin recipients, with a p value of <0.007 in Study 003, and 76.7% in the fidaxomicin arm and 63.3% in the vancomycin arm, with a p value of <0.001, in Study 004.

FDA agreed with that assessment following three sensitivity analyses, which changed the numbers but not the conclusion.

The agency also accepted that the antibiotic is non-inferior to vancomycin with regard to clinical cure rates at the end-of-treatment visit - the primary endpoint - with rates of 88% and 87% in the two studies, compared to 84% and 85% for vancomycin.

FDA's analysis of Optimer's non-inferiority margin, concluded that the "the historical evidence supports the applicant's proposed margin of 10% while still preserving over 60% of the treatment effect based on clinical judgment."

If FDA approves fidaxomicin, which has a PDUFA date of May 30, the drug would follow Forrest's Teflaro (ceftaroline) as the second antibiotic to be approved in the last six months (Also see "FDA Raises Breakpoints In Final Labeling For Forest's Ceftaroline" - Pink Sheet, 8 Nov, 2010.).

- Cathy Dombrowski ([email protected] )