The Liposome Company Inc. disclosed data from three Phase III trials confirming that Evacet - its liposomal formulation of the chemotherapeutic agent doxorubicin - is comparable to two other first-line treatments of metastatic breast cancer but significantly less cardiotoxic than the non-liposomal form of doxorubicin.
Lily Lee, vice president of biostatistics and regulatory affairs for the Princeton, N.J.-based company, said the trial "was to determine if Evacet was statistically significantly less cardiotoxic than doxorubicin without sacrificing efficacy. These trials show overwhelmingly that it is."
The company intends to prepare a new drug application (NDA) next month with the FDA, and will request expedited review status.
Although doxorubicin has been used against metastatic breast cancer for 36 years, it carries serious side effects, most notably damage to the heart, including congestive heart failure. Other potential side effects are severe nausea and vomiting; ulcers in the lining of the mouth, esophagus and intestines; and bone marrow suppression.
Three Trials Conducted, Two With Other Agents
Three trials were conducted: a single-agent trial, in which Evacet was compared directly to doxorubicin; a combination trial in which Evacet was compared to doxorubicin when each was administered in combination with cyclophosphamide; and a European combination trial in which Evacet was compared to Epirubicin when each was administered in combination with cyclophosphamide.
Cytoxan (cyclophosphamide) is a cytotoxic chemotherapeutic agent marketed by Bristol-Myers Squibb Co., of New York.
Epirubicin (pharmorubicin), a conventional therapy in Europe, is marketed by Pharmacia & Upjohn, of Berkshire, U.K., but is not available in the United States, although the company intends to file a marketing application with the FDA early next year.
Cardiotoxicity in the single-agent and the doxorubicin combination studies was measured by MUGA scanning - a sensitive, radioisotopic method for evaluating cardiac performance. Twenty-six percent of the patients enrolled in the single-agent study receiving doxorubicin experienced a cardiac event, as compared to 12 percent receiving Evacet. Twenty-six percent in the combination study experienced a cardiac event, compared to 9 percent receiving Evacet plus cyclophosphamide.
In the single-agent study, eight patients receiving doxorubicin developed congestive heart failure while only one taking Evacet did. In the combination study, five receiving doxorubicin plus cyclophosphamide developed congestive heart failure, compared to no patients receiving Evacet plus cyclophosmamide.
There were less severe nausea and vomiting to a statistically significant degree in the single-agent Evacet trial compared to doxorubicin patients, and a trend to less severe ulceration of the lining of the gullet.
The Liposome Company also is considering Phase IV trials that would begin next year and would use Evacet in combination with Taxol (paclitaxel) or Taxotere.
"Herceptin, which was recently approved by the FDA, was not approved for use with anthracyclines [a class of chemotherapeutic drugs], because of additional cardiotoxicities," Lee said. "This is a niche that we can move into."
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 anticancer drug Taxol is marketed by Bristol-Myers Squibb. Taxotere is marketed by the Rhone-Poulenc Group, of Cedex, France.
The Liposome Company also is considering studies of Evacet for use in the elderly population, Lee said. "We have a rich program planned for Evacet, and we are in the process of identifying key centers and sites," she added.
Doug Farrell, director of investor relations for the company, said it "has not made a final decision to market Evacet ourselves or to partner with someone else."
The new data were reported at a meeting of the European Society of Medical Oncology, in Athens, Greece.
The Liposome Company's stock (NASDAQ: LIPO) closed Tuesday at $7.75, down $0.218. n