U.S. BIOSCIENCE NEUTREXIN APPROVAL AS SECOND-LINE THERAPY FOR PCP GIVES FIRM SECOND MARKETED PRODUCT; OVER 500 PATIENTS RECEIVED DRUG UNDER TREATMENT IND

U.S. Bioscience's methotrexate analog NeuTrexin is indicated as a second-line treatment for Pneumocystis carinii pneumonia, FDA states in the Dec. 17 approval letter. The NeuTrexin approval follows an accelerated review process at the agency that lasted about 10-1/2 months. Joining the advanced ovarian cancer treatment Hexalen, NeuTrexin becomes the second U.S. Bioscience product cleared for U.S. marketing. FDA approved NeuTrexin (trimetrexate glucuronate inj.) for use with concurrent leucovorin administration "as an alternative therapy for the treatment of moderate-to-severe [PCP] in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS), who are intolerant of, or are refractory to, trimethoprim-sulfamethoxazole therapy or for whom [TMP/SMX] is contraindicated." PCP is an opportunistic infection that affects about 80% of people with AIDS. As with Burroughs Wellcome's Mepron (atovaquone), approved last November as a second-line treatment for PCP ("The Pink Sheet" Dec. 7, 1992, T&G-4), NeuTrexin studies have shown it to be better tolerated than TMP/SMX by PCP patients. However, both drugs require more patients to discontinue therapy because of lack of efficacy. West Conshohocken, Penn.-based U.S. Bioscience submitted its NDA (20-326) for NeuTrexin Feb. 1. FDA cleared the orphan product without requiring U.S. Bioscience to make any postmarketing commitments. FDA designated NeuTrexin as a "1PAAVE" drug, meaning a new molecular entity (1) given priority review (P) by the agency as a therapy for AIDS (AA), which has an orphan designation (V) and received expedited review (E). U.S. Bioscience describes NeuTrexin as a "lipophilic antifolate" which, unlike methotrexate, "can penetrate both normal cells and the cells of organisms such as Pneumocystis carinii." Concurrent administration of leucovorin (folinic acid) protects normal organs from the toxic effects of NeuTrexin, by entering normal cells via the reduced folate transport carrier located in the membrane of healthy cells, but not in Pneumocystis carinii pneumonia. NeuTrexin has been available to PCP patients under a Treatment IND. More than 500 patients received NeuTrexin under the Treatment IND, which was sponsored by the National Institutes of Health, until U.S. Bioscience announced in June that it was taking over sponsorship from NIH. NeuTrexin was originally developed as an anticancer agent, and U.S. Bioscience plans further development focusing on patients with lung cancer, prostate cancer and colorectal cancer. The company is also looking at both topical and oral formulations of the drug. U.S. Bioscience obtained exclusive license to manufacture and market NeuTrexin in countries other than Japan from Warner- Lambert, and is required to pay Warner-Lambert royalties based on net NeuTrexin sales, the company explained in its 1992 10-K filing. The agreement would terminate with regard to other countries if commercial sales do not begin within three years after U.S. sales begin. U.S. Bioscience agreed to supply NeuTrexin to Warner-Lambert's Japanese licensee for reimbursement of costs.