OT: Anidulafungin (Eraxis) As Effective As Fluconazole (Diflucan)

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Anidulafungin (Eraxis) As Effective As Fluconazole (Diflucan)

MedPage Today - Little Falls,NJ

By , Senior Staff Writer, MedPage Today

Reviewed by Jasmer, MD; Associate Clinical Professor of

Medicine, University of California, San Francisco

June 14, 2007

http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDiseas

e/tb/5935

CAMDEN, N.J., June 14 -- In a head-to-head trial, anidulafungin

(Eraxis) was at least as effective in treating invasive candidiasis

as fluconazole (Diflucan), researchers here said. Action Points

Explain to interested patients that available treatments for fungal

infections have expanded well beyond amphotericin in recent years,

first with the addition of the azole drugs and more recently with

the echinocandins.

Note that it remains unclear if there are treatment advantages that

would persuade physicians to choose one or the other.

Explain that this study shows that one of the echinocandins is at

least as effective as one of the mainstays of antifungal therapy,

fluconazole.

In another placebo-controlled randomized trial, Italian researchers

found that prophylactic fluconazole reduced the incidence of

invasive Candida infection in low-birth-weight babies.

The industry-sponsored randomized trial also found that adverse

events were similar after treatment with the two drugs, according to

Annette C. Reboli, M.D., of the University of Medicine and Dentistry

of New Jersey, and colleagues.

A successful outcome was seen in 75.6% of the patients in the

anidulafungin group, compared with 60.2% of the patients in the

fluconazole group, they reported in the June 14 issue of the New

England Journal of Medicine.

Although the percentage difference was high enough to suggest that

the anidulafungin actually led to a significantly better response

rate (at P=0.01), the finding should be treated " cautiously, " the

researchers said.

For one thing, they said, removing the study site with the highest

enrollment reduced the difference in response, implying that there

may be heterogeneity in the treatment effects. Also, they said, the

robustness of the findings may be limited by the small size of the

sample -- 245 patients.

The result will be " disappointing to those who sought a clear

winner, " said Jack Sobel, M.D., and Sanjay Revankar, M.D., both of

Wayne State University School of Medicine in Detroit.

Drs. Sobel and Revankar, writing in an accompanying editorial, noted

that there is a " paucity of data " comparing the new echinocandins

and the azole drugs, specifically fluconazole.

What data there are, they said, form " absolutely no justification

for abandoning fluconazole, given its safety, overall efficacy, and

low cost. " The prices of the echincocandins remain " several-fold

higher " than generic fluconazole, they said.

In the study by Dr. Reboli and colleagues, patients with invasive

candidiasis were randomized to intravenous treatment with either

anidulafungin or fluconazole for 10 days, followed by oral

fluconazole if needed.

The primary end point was both a clinical response and a

microbiological response at the end of intravenous therapy and a

successful outcome was achieved in 96 of 127 anidulafungin patients

and in 71 of 118 fluconazole patients.

However, one of the 47 participating sites enrolled 25 patients --

or 10% of the intent-to-treat population -- and saw a 93.3% response

to anidulafungin, compared to a 50% response to fluconazole.

When the data from that site was removed, Dr. Reboli and colleagues

said, anidulafungin was no longer significantly better than

fluconazole, although it remained non-inferior.

Their study is the first of two in the journal that deals with the

treatment of Candida species. In a placebo-controlled randomized

trial, Italian researchers found that prophylactic fluconazole

reduced the incidence of invasive Candida infection in low-birth-

weight babies.

Paolo Manzoni, M.D., of Sant' Hospital in Turin, Italy, and

colleagues of randomized 322 babies whose weight at birth was less

than 1,500 grams to get either a placebo or fluconazole at either

three or six milligrams per kilogram of bodyweight.

Treatment was continued for 30 days from birth or 45 days in the

case of infants born weighing less than 1,000 grams.

The researchers found:

In the fluconazole group, only 9.8% of the infants getting six

milligrams and 7.7% of those getting three milligrams were colonized

by Candida, compared with 29.2% in the placebo group. The difference

was significant at P<0.001 for both groups versus placebo.

Of those in the placebo group, 13.2% had invasive fungal infection,

compared with 2.7% in the six-milligram group and 3.8% in the three-

milligram group. The differences were significant at P=0.005 and

P=0.02, respectively.

On the other hand, the use of the drug did not alter the progression

from colonization to subsequent invasive disease, the researchers

said. Mortality was similar in both groups.

The study confirms previous work, according to editorialists Drs.

Sobel and Revankar, and will probably not result in a change to the

standard " wait and see and treat early " approach now used in

neonatal intensive care units.

The comparison study was supported by grants to participating

institutions from Vicuron Pharmaceuticals (now part of Pfizer),

which makes anidulafungin. Dr. Reboli reported financial links of

various kinds with Vicuron, Pfizer, Astellas, and Merck. Other

authors reported links to Pfizer, Merck, Astellas, Basilea

Pharmaceutica, Schering-Plough, Eli Lilly, Hospira, the Department

of Veterans Affairs, Hoffmann-La Roche, the Canadian Institutes for

Health Research, the Physicians Services Incorporated Foundation,

Vical, Salix Pharmaceuticals, and ViroPharma. Several of the authors

are employees of the sponsor and hold equity or stock options in the

company, including Wible, Beth Goldstein, Ph.D.,

Schranz, M.D., Krause, M.D., and Walsh, M.D.

The prophylaxis study was supported by Pfizer Italia. The authors

reported no potential conflicts.

Dr. Sobel reports financial links of various kinds with Astellas,

Pfizer, Merck, Ortho-McNeil, and Schering-Plough. Dr. Revankar

reports a speaking fee from Astellas.

Additional General Infectious Disease Coverage

Primary source: New England Journal of Medicine

Source reference:

Manzoni P et al. " A Multicenter, Randomized Trial of Prophylactic

Fluconazole in Preterm Neonates. " N Engl J Med 2007;356:2483-95.

Additional source: New England Journal of Medicine

Source reference:

Reboli AC et al. " Anidulafungin versus Fluconazole for Invasive

Candidiasis. " N Engl J Med 2007;356:2472-82.

Additional source: New England Journal of Medicine

Source reference:

Sobel JD and Revankar SG. " Echinocandins -- First-Choice or First-

Line Therapy for Invasive Candidiasis? " N Engl J Med 2007;356:2525-

26.