MedKoo product information:

OSI-7904L

GW1843 (1843U89) is a potent, 3-methyl-substituted benzoquinazoline folate analog very specific for thymidylate synthase. GW1843 was in  in clinical development. 

Gilead licensed the compound GW1843 from GlaxoWellcome and Glaxo Group Limited (now GlaxoSmithKline) in December 2000 and reformulated the product into a liposome (now re-named GS7904L) with the goal of enhancing its antitumor activity. Both GW1843 and its liposomal formulation GS7904L have demonstrated activity in human tumor cells in vitro and antitumor activity in human tumor xenografts in mice. In the xenograft studies, the liposomal formulation showed superior efficacy. Under the terms of the agreement with GlaxoWellcome, Gilead acquired exclusive, worldwide development and commercialization rights to the compound. GS7904L is a thymidylate synthase inhibitor and belongs to the same class of agents as the anticancer drug 5-fluorouracil (5-FU). 5-FU is one of the most prescribed chemotherapeutic drugs in the world and is used for the treatment of patients with colon, breast, head and neck, stomach and pancreatic cancers. GS7904L has demonstrated potent activity in a variety of preclinical cancer models including colorectal, ileocecal and ovarian cancers. [source: http://www.allbusiness.com/medicine-health/medical-science-medical-research/6190724-1.html].

On Monday, November 26, 2001, Gilead and OSI Pharmaceuticals (Nasdaq:OSIP) announced the signing of an agreement for OSI to acquire Gilead's pipeline of clinical candidates in oncology and Gilead's Boulder, Colorado operations, including clinical research and drug development personnel and infrastructure. In consideration of these assets, OSI will pay to Gilead $130 million in cash and $40 million in shares of OSI common stock upon the closing of the transaction. OSI will also pay to Gilead up to an additional $30 million in either cash or a combination of cash and OSI common stock upon the achievement of certain milestones. The transaction is expected to close by year-end.

Interim clinical trial results: Twenty-seven patients were treated with 101 total courses of CDDP/OSI-7904L. Dose-limiting toxicity was observed in 2 patients in the CDDP/OSI-7904L 60/12 mg/m2 cohort. One patient experienced rash, stomatitis, dehydration, renal failure, hyperbilirubinemia, and fatal neutropenic sepsis, whereas the other patient experienced grade 3 nausea, vomiting, and ileus. Therefore, the CDDP/OSI-7904L 60/9 mg/m2 cohort was expanded, with 2 of 6 patients reporting significant fatigue. Other toxicities were mild or moderate. Intermediate dose levels of 60/7.5 and 75/7.5 mg/m2 were evaluated, and the latter was identified as the recommended dose for phase II studies. No major pharmacokinetic interactions between CDDP and OSI-7904L were observed. Three patients had partial responses (gastric adenocarcinoma and heavily pretreated breast cancer). There was no significant relationship between baseline homocysteine and toxicity. CONCLUSIONS: The recommended doses for CDDP and OSI-7904L administered once every 3 weeks are 75 and 7.5 mg/m2, respectively. Pharmacokinetic interaction between the agents was not apparent. Preliminary clinical activity was observed in breast and gastric cancer. [source: Clin Cancer Res. 2008 Dec 1;14(23):7947-55.]

Current developer: GlaxoWellcome, Gilead Sciences, Inc. and  OSI Pharmaceuticals

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