Pfizer may change its enrollment goal for a Zyvox study depending on FDA's modification of its 1999 guidance on catheter-related bloodstream infections (CRBSI).

Pfizer has enrolled approximately 600 patients in its Phase III study of Zyvox (linezolid) for catheter-related infection. The company would like to see enrollment reach 980 patients.

Although Pfizer's enrollment of 600 patients is the largest enrollment to date for the indication, FDA's current guidance calls for two studies with 1,960 patients. At its current enrollment rate of 7.6%, the company would need to screen 25,654 patients to reach to that figure.

The company has been enrolling patients in the 24-center, randomized, controlled Phase III study since early 2002. The study compares the safety and efficacy of linezolid to vancomycin.

If the agency allows companies to present data on catheter-related infections as well as relevant indications for a CRBSI indication, then Pfizer will likely end its study and begin analyzing the data. The company has sufficient complementary data on complicated skin infections.

FDA convened the Anti-Infective Drugs Advisory Committee to discuss altering the guidance due to difficulties in carrying out clinical trials for CRBSI (¹ Also see "FDA Moving Forward On Primary Bacteremia Indication" - Pink Sheet, 1 November, 2004., p. 30). [Editor's Note: To ² watch a webcast or order a video/DVD of this meeting, visit FDAAdvisoryCommittee.com.]

The committee suggested three ways FDA could alter the guidance: randomized trials with active control, non-inferiority margins in the range of 5%-10% and allowing for 48 hours of prior therapy instead of the current 24-hour recommendation to encourage increased enrollment.

Zyvox is currently approved for the treatment of nosocomial and community-acquired pneumonia, and skin and skin structure infections.

Pfizer is still in the process of finalizing the study's primary endpoint. The CRBSI ³ guidance recommends: "A composite endpoint (i.e., clinical and microbiologic response) at the test-of-cure visit will be the primary endpoint in the final regulatory decision, with differences in all-cause and/or infection-related mortality rates also considered."

Vicuron has completed a Phase II study of dalbavancin in CRBSI but believes it cannot advance the drug to a Phase III study under the guidance's current trial design criteria.

The study compared the efficacy and safety of dalbavancin to vancomycin in 67 patients. Patients were randomized to dalbavancin 1 g IV on day 1 and 500 mg IV on day 8 compared to vancomycin 1 g IV b.i.d. for 7-14 days.

The primary endpoint was overall (clinical and microbiological) response at follow-up, 21 days after end of therapy, in the microbiological intent to treat population with a baseline causative pathogen and at least one dose of study drug.

At follow-up, overall response was 87% for the dalbavancin arm compared to 50% for the vancomycin arm. Clinical response was 87% for the dalbavancin arm compared to 50% for the vancomycin arm, and microbiological response was 96% for the dalbavancin arm compared to 79% for the vancomycin arm.

The proportion of patients with adverse events was similar across the arms. Ten patients on the dalbavancin arm experienced adverse events compared to six on the vancomycin arm.

The most common adverse events on the dalbavancin arm were oral candidiasis, diarrhea, constipation and increased body temperature. For the vancomycin arm it was oral candidiasis.

Cubist is not pursuing a CRBSI indication for Cubicin (daptomycin). "The Pink Sheet" incorrectly reported the indication in a previous story (⁴ Also see "Primary Bacteremia Due To S. Aureus Indication Finds Minimal Cmte. Support" - Pink Sheet, 18 October, 2004., p. 31).

Cubist is currently involved in a Phase III study of Cubicin in infective endocarditis/bacteremia due to Staphylococcus aureus. The company has also experienced difficulties related to study enrollment. Of more than 5,000 patients screened, roughly 200 have been enrolled.

Pfizer Zyvox Study Of Catheter-Related Infections May Lower Enrollment Goal

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