Naproxcinod: AZD 3582, HCT 3012, naproxen nitroxybutylester, nitronaproxen, NO-naproxen

Naproxcinod is a derivative of naproxen with similar anti-inflammatory activity, but less gastrointestinal toxicity. It is the first of a new class of analgesic and anti-inflammatory drugs known as cyclo-oxygenase-(COX)-inhibiting nitric oxide donators (CINODs) under development with NicOx in several countries. Naproxcinod is in phase III clinical development in the US for the treatment of osteoarthritis. The improved gastrointestinal tolerability of naproxcinod appears to be due to its release of nitric oxide (NO) and the consequent maintenance of tissue perfusion and integrity. Naproxcinod is available for licensing.AstraZeneca had been a worldwide licensee for naproxcinod and other CINODs. However, the results of phase II clinical trials of naproxcinod did not fulfill AstraZeneca's strategic commercial criteria for further investment and NicOx reacquired rights following AstraZeneca's decision to discontinue its involvement in 2003. NicOx was surprised by AstraZeneca's decision, and remained fully convinced of the potential of naproxcinod. NicOx is seeking new partners for development of compounds of the CINOD class. The second phase III trial (302 study) for naproxcinod in patients with osteoarthritis of the knee was initiated in April 2007. The trial will enrol approximately 1020 patients from 120 clinical sites in the US. The study is designed to confirm naproxcinod's efficacy and provide additional blood pressure data. Efficacy results are expected in mid-2008. The third phase III trial (303 study) is scheduled to start in the first half of 2007 and will assess the efficacy and safety in patients with osteoarthritis (OA) of the hip. Following pooled analysis of all three phase III trials, NicOx hopes to file an NDA in the US during the first quarter of 2009.NicOx is in ongoing discussions with regulatory authorities worldwide regarding the safety of naproxcinod and its COX-inhibiting properties. The company submitted documentation to the US FDA in August 2006 that outlined the long-term safety assessments planned for naproxcinod and has requested scientific advice on naproxcinod from the EMEA in Europe. Pending successful outcomes of the three phase III trials in patients with OA, the company anticipates that regulatory submissions in the US and Europe could be made during Q1 2009. NicOx is planning to validate a proposed development plan for Japan with the Japanese authorities in Q1 2007. Another monitoring trial is being planned by NicOx: the 305 study is a clinical endoscopy study whose objective is to confirm previous clinical findings that treatment with naproxcinod results in less gastrointestinal damage than naproxen. The trial is expected to start in 2007. The STAR Multinational Study Group has conducted a phase II gastrointestinal safety and efficacy study of naproxcinod versus naproxen in 970 patients with osteoarthritis at 80 sites in Argentina, Brazil, Hungary, Mexico, Norway, Poland, South Africa and the UK. The study was completed in November 2002.Previously, AstraZeneca had conducted a randomised, phase II trial evaluating naproxcinod's efficacy and safety among 672 subjects with symptomatic knee osteoarthritis.