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.