ROCKVILLE, Md. -- A Food and Drug Administration advisorycommittee on Friday failed to recommend approval of U.S.Bioscience Inc.'s Ethyol as a treatment to protect healthy cellsfrom chemotherapy.
The Oncology Drugs Advisory Committee made 12recommendations in response to the company's presentation ofdata from preclinical and clinical trials of Ethyol, some of whichare continuing.
The committee action took place after the markets closed. Thestock (AMEX:UBS) closed down $1.50 at $31.50.
The set of decisions "adds up to a recommendation not toapprove the drug at this time, because there aren't two studiesthat support Ethyol's (reduction of) toxicological effects, andthere is insufficient evidence that Ethyol does not decrease theanti-tumor effect of chemotherapy," said Dr. Robert Temple,director of the FDA's Office of Drug Evaluation I.
Apparent confusion between the agency and the companyresulted in the presentation of data that the committee deemedunsuitable for analysis.
U.S. Bioscience sought approval of Ethyol for protection ofchemotherapy patients who are at risk for serious toxicitiesfrom conventional doses of cyclophosphamide (CP) or CP incombination with cisplatinum.
The company failed to resolve doubts about clinical trials dataand study design, said committee Chairman Dr. CraigHenderson, associate professor of medicine at Harvard MedicalSchool. "We certainly feel that additional studies need to bedone," he said.
Dr. Robert Capizzi, executive vice president for research anddevelopment, told BioWorld that the timing for anotherattempt for approval will depend on "dialogue with the FDA."Said Capizzi, "We are continuing our studies of Ethyol, and wehave other studies in the pipeline, preliminary analysis ofwhich looks very promising."
A key reason for the failure was the second use before thecommittee of trial data based on interim end points, Hendersonsaid. "Whenever a drug company terminates the process anddecides they are going to speed it up, they have to have datathat is so overwhelming, even its strongest enemy is convincedby it," he said.
Several months ago, the company presented interim resultsfrom a trial in which CP was used with or without Ethyol totreat 63 patients with ovarian cancer, he said. According toHenderson, U.S. Bioscience claims the FDA recommended that itadd patients to the trial and then allow the FDA to take another"interim look" at its results. However, Henderson told BioWorld,FDA staff members maintain that they recommended that thetrials first be completed.
Committee member Dr. Steven Piantadosi, associate professorof oncology and biostatistics at Johns Hopkins Oncology Center,suggested conducting an entirely new study to verify theovarian cancer trial. "We have analyzed the study using aninterim analysis method whose qualities we don't know andcan't quantify," he said.
The committee unanimously recommended that U.S. Biosciencecomplete its ovarian cancer trial. It also unanimously agreedthat data demonstrated Ethyol's effectiveness in reducinghospitalization for febrile granulocytopenia, but did notdemonstrate effectiveness against neurotoxicity, nephrotoxicityor ototoxicity caused by CP or CP and cisplatinum. Thecommittee voted 7-1 to recommend additional studies to showwhether Ethyol decreases the toxicities of cisplatinum.
Due to inadequacies in study design, the committee agreedunanimously that it could not draw conclusions from a secondclinical trial of Ethyol's effect on the toxicity of Cytoxan CP, anda third trial of Ethyol administered with cisplatin for thetreatment of melanoma.
-- Kris Herbst BioWorld Washington Bureau
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