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BiotechTracker: NicOx Aspirin Derivative Is Easier on the Stomach   
September 08, 2003  NicOx (Paris: NCOX) has an expansive developmental portfolio featuring compounds related to the biology of nitric oxide (NO). The subject of Nobel prize-winning work, NO’s therapeutic promise is extensive, with opportunities in the management of cancer, infectious and non-infectious inflammation, atherosclerotic cardiovascular disease, pulmonary hypertension, septic shock, respiratory disorders, anticoagulation, and cognitive impairment. NicOx’s NCX-4016, an NO-releasing aspirin derivative, is in phase II clinical trials for the treatment of cardiovascular diseases including thrombosis, complications of endothelium-related diseases such as diabetes, and other vascular disorders such as restenosis. NCX-4016 is featured in the on line editions of Proceedings of the National Academy of Sciences as a promising gut protective agent for patients who regularly use a cyclooxygenase-2 (COX-2) inhibitor. The results also show that the cardioprotective effects of the aspirin component of NCX-4016 require continued investigation in this setting. 

Stefano Fiorucci and colleagues were particularly concerned that COX-2 inhibitors can exacerbate aspirin-induced stomach lining damage. This is particularly important in the every day management of individuals required to take a COX-2 inhibitor for the chronic management of inflammatory disorders such as rheumatoid arthritis and concomitant aspirin for cardiovascular event risk reduction. Preclinical and early clinical trial work had demonstrated that NCX-4016 has the antiplatelet activity of a cardiovascular protectant without the degree of gut damage risk associated with aspirin. The research team studied 32 healthy volunteers given 2 weeks of either NCX-4016 800 mg twice daily or aspirin 100 mg daily, alone or in combination with Pfizer’s (NYSE: PHE) Celebrex 200 mg twice daily. 

The mean gut mucosal injury score was 5.8 ± 1.8 in aspirin recipients, and 2.4 ± 0.7 in NCX-4016 recipients. Celebrex administration raised the gut injury score of aspirin recipients (9.9 ± 1.9) but not of NCX-4016 recipients (1.5 ± 0.8). Gut injury scores averaged 5.8 for aspirin monotherapy recipients and 2.4 for NCX-4016 recipients. Aspirin plus Celebrex co-administration was associated with a significantly higher average gut injury score of 9.9, but for NCX-4016 plus Celebrex, the score did not differ significantly from that associated with NCX-4016 monotherapy. Specific biochemical profiles and correlations to therapeutic response added significant biological confirmation that the tested hypothesis was appropriately investigated. 

In addition to NicOx, companies with compelling therapeutic NO programs include Schering (NYSE: SHR), Aventis (NYSE: AVE), AstraZeneca (NYSE: AZN), Medinox (privately held), NitroMed (privately held), Pfizer (NYSE: PFE), Eli Lilly (NYSE: LLY), ICOS (NASDAQ: ICOS), Bayer (NYSE: BAY), and GlaxoSmithKline (NYSE: GSK).   
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