The Liposome Co. Inc. said Wednesday that it started Phase III trialsof its liposomal doxorubicin product, TLC D-99, in metastatic breastcancer patients.

One of the pivotal trials will compare D-99 with conventionaldoxorubicin, a chemotherapy drug. The other will compare acombination of D-99 and cyclophosphamide to that drug andconventional doxorubicin. Each trial will be conducted at about 20sites and each will involve about 300 patients, said Brook Boveroux,vice president, finance, and chief financial officer of the Princeton,N.J., company.

"The focus of the trials is to demonstrate that D-99, either alone or incombination, has equivalent efficacy and a better safety profile" thanthe regimen with which it's being compared, Boveroux toldBioWorld. Enrollment is expected to take 18 months, he said, andthe trial will assess response rates, duration of response and otherendpoints.

Pfizer Inc., of New York, acquired worldwide marketing andmanufacturing rights to the product in 1990. The companies have ajoint development program in which Pfizer is picking up Liposome'sshare of development costs. Liposome will get a royalty on sales andundisclosed milestone payments. Boveroux said no milestone wasreached with the start of the Phase III trials.

"Clearly," he said, "we think it's going to be an important drug. It'ssignificant that Pfizer has taken this with us and started Phase III.They don't make those decisions lightly."

Doxorubicin is one of the world's most widely usedchemotherapeutic agents, but its use is limited by its side effects,including irreversible cardiotoxicity. Liposome hopes to treat thetumor as effectively while minimizing damage to the heart.

A Phase II study of TLC D-99, conducted at the M.D. AndersonCancer Center and presented last spring, evaluated 41 patientstreated with D-99, cyclophosphamide and fluorouracil. Of the first23 evaluable metastatic breast cancer patients, 16 had a partialresponse (tumor reduction of more than 50 percent), four were stableand three had disease progression, Boveroux said.

Investigators reported that the liposomal encapsulation ofdoxorubicin appeared to allow administration of higher cumulativedoses.

Liposome has a Phase II, high-dose program with D-99, comparing itto the highest dose that can be given of doxorubicin. Both are beinggiven with support of granulocyte colony stimulating factor. Theobjective is to demonstrate equivalent safety but better efficacy.

The company also has other Phase II studies ongoing in other solidtumors.

Its lead product, amphotericin B Lipid Complex (ABLC), is in PhaseIII trials in the U.S. for patients with aspergillosis refractory tostandard therapy, and in a comparative study to determine theeffectiveness of ABLC vs. amphotericin B in treating fungalinfections in patients receiving cancer chemotherapy or bone marrowtransplants.

Liposome has filed for marketing approval of ABLC in eightEuropean countries, and plans to seek approval in 10 other countries,Boveroux said. It plans to file for U.S. approval late in 1995. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.