The acceptance of The Liposome Co. Inc.'s new drug application forits amphotericin B lipid complex makes the Princeton, N.J., companythe U.S. front-runner in liposome-related products for systemic fungalinfections.
The Liposome Co.'s (TLC) application, filed in May, was accepted forreview by the FDA Thursday. It marks the first filing in the U.S. of alipid-based amphotericin product. TLC is seeking approval of theproduct, ABLC, specifically for the treatment of aspergillosis inpatients who have failed conventional therapy or who have liverimpairments.
The company already has the drug approved in the U.K. andLuxembourg, under the name Abelcet, and has applications pending ina number of other countries. Aspergillosis represents the second largest(to candidiasis) infection market.
"This is one of the most important events in the company's history[which dates to 1981]," said Brooks Boveroux, TLC's vice president offinance and chief financial officer. "In a very aggressive time framesince we reacquired the product two and a half years ago, we totallychanged the development strategy. We've got significant manufacturingcapacity and we are building a marketing organization. We'retransforming from a research and development company to apharmaceutical manufacturing and marketing organization."
TLC has tested ABLC in other fungal infections, though Boverouxwouldn't reveal its strategy as far as seeking approval in otherindications. He said, however, that data would be submitted forpublication.
Marc Ostro, vice president and biotechnology analyst for New York-based UBS Securities, said he doesn't foresee problems with the filingand expects a fairly quick FDA review. If approved, he said he wouldexpect more off-label use than on-label because of the toxicityproblems associated with generic amphotericin B.
TLC's lipid-based product consists of bound lipids and drug thatseparate, or release, at the point of infection. Boveroux said trials haveshown response rates of 60 percent in refractory aspergillosis patients,and greater response rates in other infections.
Two other lipid- or liposome-based antifungal drugs are in late stagetesting in the U.S.: Boulder, Colo.-based NeXstar PharmaceuticalsInc.'s AmBisome and Amphocil from Sequus Pharmaceuticals Inc.(formerly Liposome Technology Inc.), of Menlo Park, Calif. All threeamphotericin B products are approved in various countries outside theU.S. AmBisome, the first on the market, is the leading seller.
All three also have formulations of anti-cancer drugs in development.Earlier this month an FDA advisory committee recommended approvalof NeXstar's DaunoXome, and in February the panel recommendedSequus' Doxil for accelerated approval.
"The technology is finally coming of age, and there will be products onthe market based on liposomes," Ostro said. "There aren't too manysegments of the biotech industry for which you can say that."
Ostro said TLC's filing in aspergillosis was a good move because ofthe large market, the life threatening nature of the disease, and becausePfizer Inc.'s approved drug, Diflucan, doesn't work for that condition.He said it is likely ABLC will be the first lipid-based antifungal on themarket, which could be a coup for TLC.
"It's going to depend on how well they market the product," Ostrosaid. "If they do a good job they can get a strangle hold on the market."To that end, he said, "They've hired some very good people to runmarketing and sales."
Ostro said the three amphotericin products are different, and"ultimately the winners and losers will be based not just on timing andmarket strategy but how the drugs work." Each of the products isapproved but direct comparisons can only be made through theavailable clinical trial data, since a comparative study has not been run.Ostro would like to see a study offering direct comparisons, and saidhe expects a clinician eventually will do that whether the companieslike it or not.
Ostro sees TLC _ which now has about $80 million in cash _reaching profitability in 1997, and becoming a top-tier biotechnologycompany. NeXstar, he said, will increase sales of AmBisome outsidethe U.S., and probably be profitable sometime in 1997. Sequus' maindraw is Doxil, although indications beyond Kaposi's sarcoma areunclear, Ostro said. "If [Sequus] solves its balance-sheet problems,they will probably make it as well," he said.
One product that differentiates TLC, Ostro said, is TLC C-53, a drugaimed at adult respiratory distress syndrome and other diseases that hashome run potential. Boveroux said TLC is meeting with the FDA thismonth to discuss the protocol and expects to start a pivotal trial by theend of the year. TLC D-99, the company's doxorubicin drug, is inPhase III comparative trials.
TLC's stock (NASDAQ:LIPO) gained 6 cents after Thursday'sannouncement and another 56 cents Friday, closing at $11.93 pershare. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.