WASHINGTON - The third time was the charm for U.S. BioSciencewhen the Oncologic Drugs Advisory Committee (ODAC) on Fridayunanimously recommended FDA approval of Ethyol (amifostine), aselective cytoprotective agent.

Twice before U.S. BioScience failed to convince ODAC of the meritsof Ethyol. The panel in December 1994 and January 1992 rejectedU.S. BioScience's previous applications. (See BioWorld Today, Dec.13, 1994, p. 1.)

The positive review of Ethyol marked the second drug in as manydays to be recommended by ODAC. On its first day of deliberations,ODAC approved NeXstar Pharmaceuticals Inc.'s DaunoXome, aliposomal formulation of the anticancer agent daunorubicin as a first-line therapy for treatment of advanced Kaposi's sarcoma.

Approval of Ethyol is expected to open up a $200 million market forU.S. BioScience, a pivotal event for a company about to run out ofcash, Alex Zisson, an analyst with Hambrecht & Quist in New York,said in an interview with BioWorld Today.

"The decision will prove the key to keeping the company viable,"Zisson said. "Right now, Ethyol is the only protective agent available.The potential market for Ethyol, when used as a protective agent forovarian cancer patients receiving cisplatin, is $200 million," saidZisson.

"The market will expand considerably when you count off-label useand that additional markets that will open up when U.S. BioSciencecompletes the studies on Ethyol's potential to improve thechemotherapy treatment outcomes of patients with other types ofcancer," Zisson said.

AMEX suspended trading on U.S. BioScience's stock Fridaymorning. Trading is expected to resume today.

Noting that U.S. BioScience was about to run out of cash, Zisson saidhe expected that the FDA should finish final approval of Ethyol'slabeling, promotional materials and other regulatory issues within sixto nine months.

"U.S. BioScience already has its manufacturing plant approved. Theyare set to hit the ground running," Zisson said.

ODAC Chairman Charles Schiffer, professor of medicine at theUniversity of Maryland Cancer Center in Baltimore, told BioWorldToday that the committee approved U.S. BioScience's thirdsubmission for Ethyol because "the science was better. Companyofficials focused on one point. The confounding issues [ofmultiplicity of effects] were addressed. In their last presentation, theyaddressed three or four issues at once," he said.

"A focused presentation was the key to our success," said PhilipScheine, chairman and CEO of U.S. BioScience. "Unlike theprevious two applications, we focused on the issue of the Ethyol'sprotective effect on the cumulative toxicity of cisplatin."

Scheine said he was not displeased that ODAC had given Ethyol onlyconditional approval when used to treat patients with cancers otherthan ovarian. "We intend to sit down with FDA and work out how westudy the other patient populations."

He added that patient accrual will be difficult for some indications,such as testicular cancer which is much less prevalent than ovariancancer.

During Friday's deliberations, the committee voted 8-0 to placeEthyol on the accelerated drug approval track but asked foradditional studies.

Accelerated review means that new drugs can be brought to marketfaster if they demonstrate meaningful therapeutic benefit overexisting therapies for patients with serious or life-threateningconditions. Fast track drugs are subject to post-marketingsurveillance.

The committee split 4-4 on whether to approve Ethyolunconditionally.

The FDA will make the final decision about whether to put Ethyol onthe fast track or give it unconditional approval.

The two votes now give FDA officials considerable latitude inapproving the product labeling. How the agency writes the labelingof course determines how it will be used by clinicians and affects itspotential markets.

The agency could approve Ethyol unconditionally for use as acytoprotective agent in patients with advanced ovarian cancer treatedwith cisplatin doses of 100mg/m2 for six courses of therapy. Or theagency could approve labeling that says the product wasconditionally approved because additional studies must be completedbefore Ethyol is indicated in treating patients with other types ofcancer.

The second categorization would open up Ethyol to more marketsand perhaps more off-label use, said Zisson.

Schiffer wanted the labeling to be flexible enough to reflect widevariations in physician practice. Oncologists traditionally have reliedon off-label uses of chemotherapy agents.

FDA reviewer Robert Temple at the ODAC meeting noted that thereis considerable disagreement in the medical community on whether100mg/m2 of cisplatin is the standard dose to treat patients withadvanced ovarian cancer. "Taxol used in combination with cisplatinmay become the standard of care," Temple noted.

U.S. BioScience was complimented by several ODAC members forthe quality of its presentation and objectivity of its science. EvenFDA reviewer Robert DeLap in his presentation on Ethyol usedseveral of the manufacturer's slides to illustrate his review. DeLapoffered no substantive criticism of the manufacturer's findings. n

-- Michele L. Robinson Washington Editor

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