NicOx S.A. announced positive clinical endoscopic results with NCX 4016, in development for the treatment of cardiovascular diseases, demonstrating gastro protection even when co-administered with celecoxib. In contrast, the commonly prescribed combination of low dose aspirin with celecoxib aggravated gastric damage. The results were presented at Digestive Disease Week 2003 (May 17-22, 2003, Orlando, Florida).

Since their launch in 1999, COX-2 selective NSAIDs have become a treatment of choice for pain and inflammation, particularly in arthritis. Subsequent clinical experience suggests a possible link between the use of COX-2 selective NSAIDs and an increased risk of non-fatal myocardial events. Recent evidence has also shown that arthritic patients have a high prevalence of cardiovascular risk factors and low dose aspirin anti-platelet therapy is frequently prescribed to counter this. However, it appears from large multicentre trials that co-administration of celecoxib, the selective COX-2 inhibitor, with low dose aspirin increases gastric damage.

In the study presented, 32 volunteers were randomised to receive two weeks of treatment with NCX 4016 (800 mg bid) or aspirin (100 mg o.a.d.) alone

or in combination with celecoxib (200 mg bid). Gastrointestinal mucosal damage was assessed by endoscopy. The endoscopic results showed that celecoxib almost doubled the gastrointestinal injury caused by aspirin, while gastric protection was maintained with NCX 4016.

These clinical results are supported by preclinical studies also presented at Digestive Disease Week 2003, showing that aspirin interacts with COX-2 selective NSAIDs to aggravate gastric damage and inflammation, in marked contrast to NCX 4016 which did not cause gastric damage alone, or in co-administration with a COX-2 selective NSAID.

Michele Garufi, chairman and CEO of Nicox S.A., commented: "This new clinical study with NCX 4016 is a further proof of concept that our nitric oxide donating technology generates novel drug candidates with excellent gastric safety. These new endoscopic results with NCX 4016 are particularly relevant considering that a significant number of patients taking COX-2 selective NSAIDs could benefit from a cardiovascular drug that can be safely co-administered. NCX 4016 is currently in Phase II clinical development for the treatment of peripheral cardiovascular diseases and this study confirms the broad safety profile of our compound."