By Lisa Seachrist
WASHINGTON - The Liposome Co. has filed a new drug application for Evacet, its liposomal formulation of the cancer drug doxorubicin, as a first-line therapy for the treatment of metastatic breast cancer.
Princeton, N.J.-based Liposome has requested an expedited review and hopes to see Evacet in the marketplace by the end of 1999. The FDA has yet to decide whether to grant the product expedited review.
Most women who have metastatic breast cancer will receive doxorubicin. However, Lawrence Hoffman, vice president and CFO for Liposome, told BioWorld Today, "Doxorubicin has been around since the 1960s. Our Phase III studies show that Evacet has significantly reduced cardiotoxicity compared to doxorubicin."
Doxorubicin is a derivative of an antibiotic that has anticancer activity. It has been used in the treatment for metastatic breast cancer for 36 years. However, doxorubicin carries with it serious and debilitating side effects, including severe nausea and vomiting, ulcers of the lining of the esophagus and intestines, bone marrow suppression and, most notably, damage to the heart resulting in congestive heart failure.
Patients are most likely to develop congestive heart failure when they have received a cumulative lifetime dose of the drug exceeding 450 milligrams per meter squared.
Evacet is designed to lessen the cardiotoxicity of the drug by encapsulating the drug as a doxorubicin citrate complex in liposomes. As a result, the drug is much less likely to find its way into the heart muscle, where it can do damage. In addition, preclinical studies of the drug show it is more likely to concentrate in tumors.
"The blood vessels that supply tumors aren't as complete as those in the rest of the body," said Andrew Janoff, vice president of research and development at Liposome. "They are fenestrated and the liposomes are more likely to get from the blood vessel to the tumor."
Clinical studies show that Evacet was just as effective as doxorubicin but resulted in much less cardiotoxicity than the older drug whether it was used alone or in combination with the anti-cancer agent cyclophosphamide.
"We showed a statistically significant decrease in cardiotoxicity using Evacet," Hoffman said. "We showed a trend toward lesser side effects; however, those results weren't statistically significant."
As a result, the company is requesting a label for Evacet that would state its improved cardiotoxicity profile. In addition, the company is contemplating postmarketing studies of Evacet in combination with Taxol or Taxotere or, perhaps, Herceptin.
Herceptin, a monoclonal antibody for the treatment of metastatic breast cancer developed by Genentech Inc., of South San Francisco, won FDA marketing approval in September and was on the market in early October. The drug, however, wasn't approved for use in combination with anthracycline drugs, of which doxorubicin is a member, because of increased cardiotoxicity.
The anticancer drug Taxol is marketed by Bristol-Myers Squibb Co., of New York. Taxotere is marketed by the Rhone-Poulenc Group, of Cedex, France.
Should Evacet win FDA approval, Hoffman said the company would build on its existing sales force to market the drug in Canada and the United States while finding marketing partners for other regions of the world. Liposome has been marketing Abelcet, a lipid-based formulation of amphotericin B for the treatment of fungal infections since 1996.
While the company has yet to determine the estimated market for Evacet should it be approved, analysts have estimated that market could be worth approximately $200 million annually.
Liposome's stock (NASDAQ:LIPO) closed at $9.375 a share, up $0.0625.n