The FDA sent NeXstar Pharmaceuticals Inc. an "approvable" letterfor DaunoXome, making the anti-cancer therapy the first liposomal-based product to get a favorable review by the U.S. regulatory agencysince liposome drug delivery technology was discovered in the1980s.

DaunoXome is a liposomal formulation of the chemotherapeuticagent, daunorubicin, and was submitted to the FDA as a first-linetreatment of AIDS-related advanced Kaposi's sarcoma. The FDAnotification, announced this morning, came only a month after theagency's Oncologic Drugs Advisory Committee (ODAC)recommended approval of DaunoXome.

Joseph Alper, corporate communications director for the Boulder,Colo.-based NeXstar, said the letter indicates the FDA will clear thedrug for marketing following certification of the company'smanufacturing facility and some minor labeling changes. Inspectionof the plant is scheduled in September.

NeXstar's stock was up 14 percent by noon today, jumping $1.38 to$11.25.

NeXstar had hoped for FDA action on its DaunoXome submission bythe end of the year, but now an approval could come as early as thefall.

Also waiting for FDA approval is Sequus Pharmaceuticals Inc.'sDOX-SL, which is a liposomal form of the anti-cancer agent,doxorubicin. The Menlo Park, Calif.-based Sequus received anODAC recommendation for accelerated approval in February ofDOX-SL as a second-line therapy for AIDS- related Kaposi'ssarcoma.

Alper said the FDA's signal that it intends to approve DaunoXomedemonstrates that liposome technology has overcome concerns of thepast, particularly the issue of whether an anti-cancer agentencapsulated in a liposome is as effective as the chemotherapeuticdrug by itself.

Liposomes are considered safer than using the chemical therapyalone. NeXstar's liposome is a combination of a phospholipid andcholesterol; it concentrates the anti-cancer drug in the area of thetumor. The liposome also keeps the chemical agent in the patient'scirculation longer. Daunorubicin is a chemotherapeutic drug usedmainly in the treatment of childhood leukemia.

Alper said researchers are not sure what triggers release of the drugfrom the liposome when it gets to the tumors. But he noted NeXstarhas "filmed the liposomes fusing to the tumor cells and releasing thedaunorubicin."

Some of the FDA's past worries about liposomes were generated inpart by DaunoXome, which ODAC rejected in 1993. The problemfocused on a discrepancy in analysis of the data. While the companysaid patients experienced a 53 percent response rate to the drug, theadvisory committee interpreted the response rate at 17 percent. Thatapplication was based on data from an open label Phase II trial.

The current submission, Alper noted, includes results from acontrolled Phase III study comparing DaunoXome to the standardtherapy for AIDS-related Kaposi's sarcoma _ a three-drug regimenof adriamycin, bleomycin and vincristine.

In addition to suggesting the success of liposome technology, Alpersaid the FDA's action on DaunoXome demonstrates that "when youdo a real controlled clinical trial, like the big pharmaceuticalcompanies do, and provide the data the FDA wants, it will approve adrug, whether it's a liposome or not."

David Webber, an analyst with Alex. Brown & Sons Inc. in NewYork, said it may be too early to tell if the FDA's favorable action onDaunoXome has broader implications for liposome drug deliverysystems.

But he noted, "Lipsomes could fill an important need in gene therapyand in delivery of antisense oligonucleotides."

Sequus Promises Close Race

As for the competition among liposome companies to reach themarket first with their product, Webber said that most on Wall Streetbelieved Sequus had the edge based on its ODAC recommendation inFebruary.

But, he said that the approvable letter for DaunoXome suggests it andDOX-SL will get to market at about the same time.

Donald Stewart, Sequus' vice president of finance, said NeXstar hadthe head start with its original submission of DaunoXome.

"We expect our approval or approvable letter in the near future,"Stewart said. "We think we have a better product, so stay tuned.We'll meet them in the marketplace."

Webber said DaunoXome may have an advantage, however, becauseit's listed as a first-line therapy for the disease while DOX-SL wassubmitted as a second-line therapy.

The Liposome Co., of Princeton, N.J., also has a liposomalformulation of an anti-cancer drug in late-stage clinical development.

Webber said the projected market for DaunoXome in the U.S. is $35million to $50 million per year. The drug already has been approvedin Sweden and the U.K. is expected to clear it for marketing later thismonth. European sales of DaunoXome are expected to be about thesame as those in the U.S.

Alper said NeXstar also has Phase II trials under way usingDaunoXome for breast cancer, small cell lung cancer, leukemia andlymphoma. Results of those trials are expected early next year. n

-- Charles Craig

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

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