November 17, 2000
Study Results Published in Journal of Clinical Infectious Diseases Demonstrate That Ambisome® Has an Improved Safety Profile Compared to Abelcet®
- First Head-to-Head, Blinded Safety Comparison of Lipid-Based Amphotericin B Agents -
Deerfield, IL and Foster City, CA -- November 17, 2000
Fujisawa Healthcare, Inc. (FHI) and Gilead Sciences, Inc. (Nasdaq: GILD) today announced the publication of results of a multi-center head-to-head study comparing the use of AmBisome® (amphotericin B) liposome for injection to Abelcet® (amphotericin B) lipid complex in the empirical treatment of patients with febrile neutropenia. AmBisome is co-marketed by Fujisawa Healthcare and Gilead Sciences in the United States, and Abelcet is marketed by Elan Corporation plc. Results of the study indicate that AmBisome demonstrates an improved safety profile in a direct comparison with Abelcet with regard to nephrotoxicity and infusion-related reactions. The study was not designed to draw statistically meaningful conclusions related to comparative efficacy and, in fact, Abelcet is not labeled for the empirical treatment of febrile neutropenia.
“We have known for some time that the liposomal formulation of amphotericin B offers physicians and their patients equivalent efficacy with lower toxicity compared to conventional amphotericin B,” said Donald Buell M.D., Medical Director, Fujisawa Healthcare. “In addition, by conducting a randomized, multi-center, head-to-head trial, we have been able to provide physicians who are treating patients with life-threatening febrile neutropenia with compelling evidence that the liposomal formulation, AmBisome, is a safer therapy than the lipid complex, Abelcet.”
Results of the study, titled “A Randomized, Double-Blind Comparative Trial Evaluating the Safety of Liposomal Amphotericin B Versus Amphotericin B Lipid Complex in the Empirical Treatment of Febrile Neutropenia,” were published in the journal Clinical Infectious Diseases (volume 31, number 5: 1155-63). These data previously were presented at the Focus on Fungal Infections conference in March 1999.
In February 2000, the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application to include data from this study in the AmBisome product label.
Study Design and Results
This study enrolled 244 neutropenic patients at 18 cancer treatment centers in the United States. All patients had neutropenia with unresolved fever after three days of antibacterial therapy. Patients were randomized 1:1:1 to receive double-blind therapy of either AmBisome 3 mg/kg/day (n=85), AmBisome 5 mg/kg/day (n=81) or Abelcet 5 mg/kg/day (n=78) for up to 42 days.
The study demonstrated a significantly better safety profile for AmBisome at either 3 mg/kg/day or 5 mg/kg/day versus Abelcet 5 mg/kg/day. Patients receiving treatment with AmBisome experienced less nephrotoxicity, defined as doubling of the baseline serum creatinine, compared to patients receiving Abelcet (14.1, 14.8 and 42.3 percent, p<0.01). AmBisome was also associated with reduced overall frequency of infusion-related reactions such as chills and rigors (18.8, 23.5 and 79.5 percent on Day 1, p<0.001). Nausea and vomiting were similar across all treatment arms. Fewer toxicity-related discontinuations of therapy (12.9, 12.3 and 32.1 percent, p=0.004) were also seen in AmBisome treated patients compared to the Abelcet group. Despite significantly less nephrotoxicity of AmBisome observed at a dose of either 3 mg/kg/day or 5 mg/kg/day compared with Abelcet at a dose of 5 mg/kg/day, dose-limiting renal toxicity may still be observed.
“Head-to-head comparative trials are among the most important trials undertaken in pharmaceutical research, as they offer physicians the best evidence to help select effective therapy that also provides a better safety margin,” commented Noboru Maeda, chairman and chief executive officer of Fujisawa Healthcare. “We believe the publication of this study in a prestigious peer-reviewed journal is a significant event in the evolution of AmBisome. Since the addition of these data to the AmBisome product label earlier this year, we have already seen a movement in the marketplace by physicians to AmBisome for the treatment of life-threatening fungal infections.”
AmBisome is a unilamellar (single-layer) liposomal formulation of amphotericin B. Available in 42 countries worldwide, AmBisome is the only true liposomal formulation of amphotericin B. Fujisawa Healthcare and Gilead co-market AmBisome in the United States. The drug is marketed exclusively by Fujisawa in Canada and by Gilead or its distributors in Europe and the other remaining 40 countries in which it is approved.
AmBisome labels include indications for empirical therapy for presumed fungal infection in febrile, neutropenic patients; treatment of cryptococcal meningitis in HIV infected patients; Aspergillus species, Candida species and/or Cryptococcus species infections refractory (non-responsive) to conventional amphotericin B; and the treatment of visceral leishmaniasis. Additionally, AmBisome is recommended for the treatment of patients where renal impairment or unacceptable toxicity precludes the use of conventional amphotericin B. The recommended initial dose for empirical therapy of fungal infections is 3 mg/kg/day. Product labeling for AmBisome varies in each of the countries in which it is marketed.
AmBisome has a demonstrated superior safety profile compared to conventional amphotericin B for the empirical treatment of febrile, neutropenic patients and in the treatment of cryptococcal meningitis. In clinical trials, nephrotoxicity and infusion-related reactions were observed. Side effects associated with the use of AmBisome include, but are not limited to, chills, diarrhea, nausea and vomiting. For full prescribing information for AmBisome, please call 1-800-727-7003 or refer to www.ambisome.com.
About Fujisawa and Gilead
Fujisawa Healthcare, Inc., headquartered in Deerfield, IL, develops, manufactures and markets proprietary pharmaceutical products in the United States and abroad. Fujisawa Healthcare, Inc. is a subsidiary of Fujisawa Pharmaceutical Co., Ltd., based in Osaka, Japan. Fujisawa Pharmaceutical Co., Ltd., founded in 1894, is a leading pharmaceutical manufacturer and is actively developing its international operations in North America, Europe, and Asia. Additional information on Fujisawa Healthcare, Inc. and its products can be found on the internet at www.fujisawa.com.
Gilead Sciences, headquartered in Foster City, CA, is an independent biopharmaceutical company that seeks to provide accelerated solutions for patients and the people who care for them. Gilead discovers, develops, manufactures and commercializes proprietary therapeutics for challenging infectious diseases (viral, fungal and bacterial infections) and cancer. Gilead maintains research, development or manufacturing facilities in Foster City, CA, Boulder, CO, San Dimas, CA, Cambridge, UK and Dublin, IR and sales and marketing organizations in the United States, Europe and Australia. For more information about Gilead, visit the company's Web site at www.gilead.com.
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors that could cause actual results to differ materially from those referred to in the forward-looking statements. Such risks and uncertainties include the risk that these data will not be accepted by the medical community and that these data will not be replicated in clinical practice or in other studies. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in the Gilead Annual Report on Form 10-K for the year ended December 31, 1999 and in Gilead’s Quarterly Reports on Form 10-Q, all of which are on file with the U.S. Securities and Exchange Commission.
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