By Brenda Sandburg

U.S. Bioscience is set to launch NeuTrexin (trimetrexate glucuronate for injection)following FDA approval last Friday.

The drug is indicated for use with concurrent leucovorin as a second-line therapy fortreatment of moderate to severe Pneumocystis carinii pneumonia (PCP) inimmunocompromised patients -- including those with AIDS -- who are intolerant of orrefractory to trimethoprim/sulfamethoxazole (TMP-SMX) or for whom TMP-SMX iscontraindicated.

The drug will be available in hospitals by early January. The average price towholesalers is $41.65 for a 25-milligram vial. The average patient required three vialsper day for 21 days for a total cost of $2,600.

U.S. Bioscience has established a patient assistance program for uninsured patients whocannot afford the drug. The company will help patients explore Medicaid and other federalprograms, and if no reimbursement is available, U.S. Bioscience will provide NeuTrexinfree.

U.S. Bioscience noted that as many as 80 percent of patients with AIDS experience oneor more bouts of PCP in the course of their illness. The company estimated that one-thirdto one-half of PCP patients discontinue TMP-SMX because of side effects or lack ofresponse. TMP-SMX is marketed as Bactrim and Septra by Hoffman-La Roche and BurroughsWellcome, respectively.

The only other drug on the market for PCP is pentamidine. The leucovorin used withNeuTrexin acts to protect against potentially serious or life-threatening side effectsfrom NeuTrexin, including bone marrow suppression, oral and gastrointestinal mucosalulceration and renal and hepatic dysfunction.

NDA Submitted Last February

NeuTrexin was approved slightly less than after a new drug application (NDA) wassubmitted to FDA in February. FDA granted the drug a treatment IND in 1988 forHIV-infected patients with PCP who are refractory to or intolerant of TMP-SMX and/orintravenous pentamidine.

In anticipation of FDA approval U.S. Bioscience recently added five people to itsmarketing and sales staff for a total of 16. The company has one product currently on themarket, Hexalen (altretamine), for treatment of advanced ovarian cancer.

An oral formulation of NeuTrexin for use as a second-line treatment for prevention ofPCP is in development. U.S. Bioscience's senior vice president of finance andadministration, Robert Kriebel, told BioWorld that the company plans to begin atrial of NeuTrexin in combination with dapsone next year for first-line treatment ofcancer. In addition, the company plans Phase II trials of NeuTrexin in 1994 for thetreatment of cancer. Kriebel said the drug has shown activity against rheumatoidarthritis and psoriasis in preclinicals and the company plans to out-license the drug forthese indications.

U.S. Bioscience of West Conshohocken, Pa., also reported on its Ethyol NDA pending atFDA for use of the drug to protect healthy cells from chemotherapy. The company said FDAhas requested additional analyses and data from its ovarian cancer trial. U.S. Biosciencenoted that it recently responded to a list of questions from the European Committee onProprietary Medicinal Products concerning its Ethyol application in Europe.

FDA's Oncology Drugs Advisory Committee recommended against approval of the drug inFebruary 1992. FDA subsequently requested additional data showing that Ethyol prevents ordecreases toxicities caused by chemotherapy and does not decrease the anti-tumor effect ofchemotherapeutics. Since that time, the company accrued additional patients beyond theoriginal 120 for a total of more than 200.

U.S. Bioscience's stock (ASE:UBS) was down $1.13 a share on Monday, closing at $9.25.