"There is mounting evidence that statins exert numerous positive effects, beyond cholesterol-lowering, through stimulating nitric oxide production," commented Ennio Ongini, Vice President of Research at NicOx. "Restoring deficient nitric oxide signaling is known to reduce endothelial dysfunction, atherosclerosis and thrombosis, which represent the key processes underlying the most common cardiovascular diseases. We have demonstrated that nitric oxide donation can boost the non-lipid activities of statins in preclinical studies, suggesting that NCX 6560 could represent a new statin with broadened and increased efficacy, suitable for the preventive treatment of high risk cardiovascular patients."
Statins represent the most effective and best tolerated drugs for lowering abnormally raised cholesterol and have consequently become the world's best selling class of pharmaceuticals, with combined global sales of $20.1 billion in 2005.
"The tremendous success of the statin drugs has been built on the simple premise that lowering abnormally high cholesterol saves lives," added Maarten Beekman, Vice President of Clinical Development at NicOx. "The results of several large clinical trials support this theory, while some data suggest that statins have activities which bring clinical benefit beyond cholesterol-lowering, although these effects appear limited.
Despite the fact that statins provide some protection against cardiovascular disease, there is still a large need for new treatments capable of further reducing mortality. From this prospective, NCX 6560 represents an intriguing compound, due to the apparent ability of nitric oxide donation to augment the non-cholesterol effects of statins, and we look forward to advancing this compound into man as soon as possible."
Atherosclerotic plaques are believed to be the root cause underlying the majority of cardiovascular diseases and their development is a complicated, multi-step process, which is believed to involve both raised cholesterol levels and deficient nitric oxide signaling. The process starts with the formation of fat-containing lesions on blood vessel walls, due to abnormally high plasma cholesterol levels, which has a number of detrimental effects. These include infiltration of immune cells, inflammation and abnormal proliferation of smooth muscle cells, which are all processes which have been linked to abnormally low nitric oxide release from the endothelium. Furthermore, nitric oxide is involved in regulating vascular function and platelet activation and malfunction of these two systems can lead to disruption of the atherosclerotic plaque, clotting and an acute cardiovascular event.
NCX 6560 has the potential to become a new statin with broadened and increased clinical benefit, due to its ability to target atherosclerosis and endothelial dysfunction through a multipathway approach. The ability of the nitric oxide-donating moiety to counteract vascular inflammation and endothelial dysfunction should act in concert with the cholesterol lowering activity of the statin portion, to favorably influence the composition, structure and stability of atherosclerotic plaques.
Following its decision to move NCX 6560 into development, NicOx is presenting a series of preclinical results which support the rationale for using NicOx' nitric oxide-donating technology to develop the next generation statins. Interestingly, the nitric oxide released from NCX 6560 appears to markedly increase the non-cholesterol lowering activities of statins in each of the experimental systems tested. In each experiment, NCX 6560 is compared to the reference compound, which is a widely used statin drug:
* Superior anti-platelet and anti-thrombotic activity: Oral administration of NCX 6560 for 5 weeks was shown to be significantly better than an equivalent dose of the reference statin at inhibiting the adhesion of platelets to collagen, at a high shear rate, in two different in vivo models of hypercholesterolemia (p<0.05 compared to the reference for both models).
* Superior anti-inflammatory activity: NCX 6560 showed superior anti-inflammatory activity, compared to the reference statin, in terms of inhibition of TNF-alpha release from LPS-stimulated RAW264.7 macrophages in vitro (p<0.05 for NCX 6560 compared to vehicle, while the reference compound showed no effect).
* Superior improvement in endothelial function: Five days of NCX 6560 treatment resulted in significantly greater acetylcholine-induced relaxation of isolated aorta, as compared to an equivalent dose of the reference statin (p<0.05 compared to the reference), in an in vivo model of hypertension.
* Gold standard cholesterol lowering activity: NCX 6560 demonstrated a similar serum cholesterol lowering effect as an equivalent dose of the reference statin, in two in vivo models of hypercholesterolemia, and revealed a superior cholesterol lowering effect in a third model.
NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-driven biopharmaceutical company dedicated to the development of nitric oxide-donating drugs to meet unmet medical needs. NicOx is targeting the therapeutic areas of pain and inflammation and cardio-metabolic disease. Resources are focused on two lead compounds, naproxcinod (formerly HCT 3012), in phase 3 development for the treatment of osteoarthritis, and NCX 4016, in phase 2 for type 2 diabetes. NicOx has strategic partnerships with some of the world's leading pharmaceutical companies, including Pfizer Inc. and Merck and Co., Inc.
NicOx S.A. is headquartered in Sophia-Antipolis, France, and is a public company listed on the Eurolist of Euronext Paris (segment: Next Economy).
The elements included in this communication may contain forward-looking statements subject to certain risks and uncertainties. Actual results of the company may differ materially from those indicated in the forward-looking statements because of different risks factors described in the company's document of reference.
Source: NicOx S.A.
