FDA Wants Advice on Infection Recurrence with Fidaxomicin

The Food and Drug Administration accepts findings by Optimer Pharmaceuticals Inc. that the firm’s Dificid (fidaxomicin) is superior to vancomycin in curing Clostridium difficile–associated diarrhea and preventing its return, but the agency will ask an advisory panel on 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 C. difficile–associated diarrhea or C. difficile infection, and for reducing the risk of recurrence when it’s used for treatment of initial C. difficile infection.

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 who are considered to be at risk for recurrence. 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%-30% of those who respond to the two drugs have a recurrence of the infection within 2 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 the end of treatment and no recurrence by the poststudy visit – Optimer reported superiority for its drug.

In the modified intent-to-treat population, the global cure in Study 003 was 74.4% for fidaxomicin patients and 64.2% for vancomycin recipients (P less than .007); in Study 004, it was 76.7% in the fidaxomicin arm and 63.3% in the vancomycin arm (P less than .001).

The 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 noninferior to vancomycin with regard to clinical cure rates at the end-of-treatment visit – the primary end point – with rates of 88% and 87% in the two studies, compared with 84% and 85% for vancomycin.

The FDA analysis of Optimer’s noninferiority 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 the agency approves fidaxomicin, which has a PDUFA (Prescription Drug User Fee Act) date of May 30, the drug would follow Forest Laboratory Inc.’s Teflaro (ceftaroline) as the second antibiotic to be approved in the last 6 months.

This coverage is provided courtesy of "The Pink Sheet." "The Pink Sheet" and Internal Medicine News Digital Network are both owned by Elsevier.

The Food and Drug Administration accepts findings by Optimer Pharmaceuticals Inc. that the firm’s Dificid (fidaxomicin) is superior to vancomycin in curing Clostridium difficile–associated diarrhea and preventing its return, but the agency will ask an advisory panel on 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 C. difficile–associated diarrhea or C. difficile infection, and for reducing the risk of recurrence when it’s used for treatment of initial C. difficile infection.

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 who are considered to be at risk for recurrence. 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%-30% of those who respond to the two drugs have a recurrence of the infection within 2 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 the end of treatment and no recurrence by the poststudy visit – Optimer reported superiority for its drug.

In the modified intent-to-treat population, the global cure in Study 003 was 74.4% for fidaxomicin patients and 64.2% for vancomycin recipients (P less than .007); in Study 004, it was 76.7% in the fidaxomicin arm and 63.3% in the vancomycin arm (P less than .001).

The 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 noninferior to vancomycin with regard to clinical cure rates at the end-of-treatment visit – the primary end point – with rates of 88% and 87% in the two studies, compared with 84% and 85% for vancomycin.

The FDA analysis of Optimer’s noninferiority 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 the agency approves fidaxomicin, which has a PDUFA (Prescription Drug User Fee Act) date of May 30, the drug would follow Forest Laboratory Inc.’s Teflaro (ceftaroline) as the second antibiotic to be approved in the last 6 months.

This coverage is provided courtesy of "The Pink Sheet." "The Pink Sheet" and Internal Medicine News Digital Network are both owned by Elsevier.

The Food and Drug Administration accepts findings by Optimer Pharmaceuticals Inc. that the firm’s Dificid (fidaxomicin) is superior to vancomycin in curing Clostridium difficile–associated diarrhea and preventing its return, but the agency will ask an advisory panel on 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 C. difficile–associated diarrhea or C. difficile infection, and for reducing the risk of recurrence when it’s used for treatment of initial C. difficile infection.

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 who are considered to be at risk for recurrence. 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%-30% of those who respond to the two drugs have a recurrence of the infection within 2 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 the end of treatment and no recurrence by the poststudy visit – Optimer reported superiority for its drug.

In the modified intent-to-treat population, the global cure in Study 003 was 74.4% for fidaxomicin patients and 64.2% for vancomycin recipients (P less than .007); in Study 004, it was 76.7% in the fidaxomicin arm and 63.3% in the vancomycin arm (P less than .001).

The 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 noninferior to vancomycin with regard to clinical cure rates at the end-of-treatment visit – the primary end point – with rates of 88% and 87% in the two studies, compared with 84% and 85% for vancomycin.

The FDA analysis of Optimer’s noninferiority 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 the agency approves fidaxomicin, which has a PDUFA (Prescription Drug User Fee Act) date of May 30, the drug would follow Forest Laboratory Inc.’s Teflaro (ceftaroline) as the second antibiotic to be approved in the last 6 months.

This coverage is provided courtesy of "The Pink Sheet." "The Pink Sheet" and Internal Medicine News Digital Network are both owned by Elsevier.