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NCX 6560
NCX 6560 is an innovative nitric oxide (NO)-donating New Molecular Entity (NME) targeting cardiovascular indications. NicOx is currently evaluating select cardiovascular indications for NCX 6560 where NO donation may bring the greatest therapeutic benefits. A phase 1b study was completed in November 2009 for NCX 6560, an NO-donating atorvastatin, and met its primary and secondary objectives. In November 2010, detailed results
were presented by NicOx in an oral session of the American Heart Association (AHA) 2010 Scientific Sessions being held in Chicago, Illinois1.
NO donation from NCX 6560 is expected to enhance the pleiotropic effects of statins above and beyond lipid lowering. Preclinical studies have shown that
NCX 6560 demonstrated superior anti-thrombotic and anti-inflammatory properties, and greater effects on endothelial function than an equivalent dose of
atorvastatin. Preclinical results suggesting promising anti inflammatory and anti-atherogenic effects were also presented during the AHA 2010 Scientific
Sessions2. Additionnally, preclinical results suggesting that NO may have a beneficial effect in preventing statin-induced myopathy were presented at the European Muscle Conference in September 20113.
Phase 1b study design and results
The objectives of this three-part double-blind first-in-man study were to assess the safety, tolerability, pharmacokinetics and pharmacodynamic profile of
single and repeated escalating doses of NCX 6560. In the first part of the study, 40 healthy male volunteers received a single dose of either NCX 6560 or
placebo. In the second part, 48 male volunteers with high levels of low density lipoprotein (LDL) cholesterol received NCX 6560 (repeated escalating doses),
atorvastatin (40 mg) or placebo once-daily for 14 days.
The study met its primary objectives, as NCX 6560 appeared safe and well tolerated, with the highest tested dose of NCX 6560 (144 mg) showing a similar
safety profile to the marketed dose of atorvastatin (40 mg). The secondary objectives were also met, with single and multiple ascending doses showing a
favorable pharmacokinetic profile.
The preliminary evaluation of the cholesterol-lowering effect in subjects with high LDL-cholesterol at baseline, the most important exploratory objective,
showed strong activity for NCX 6560 with a dose-related LDL-cholesterol decrease. The highest tested dose of NCX 6560 (144 mg) reached a 57% reduction
after two weeks of treatment. No significant increase in liver enzymes was observed, even at the highest dose. NCX 6560 48 mg had the same lipid-lowering
effects as atorvastatin 40 mg despite a lower systemic exposure to atorvastatin and its active metabolites.
The third part of the study enrolled the 10 healthy male volunteers who had received the highest tolerated dose of NCX 6560 in the first part of the study.
The volunteers stayed in the same treatment arm (NCX 6560 or placebo) but the dose was administered following a high-fat breakfast. No apparent food effect
was observed for NCX 6560.
Out-licensing opportunities
NicOx is currently seeking partners to advance the clinical development of NCX 6560 (more information on programs open for
collaboration).
1 Djian JP, Maucci R, Guilmin L, Ferreira T, Pfister P, Abstract 14267: NCX 6560, a Novel Nitric Oxide Donating Atorvastatin With a Promising Safety
and Efficacy Profile: A Randomised, Double Blind Placebo and Active Control Study, Circulation 2010, 122, A14267.
2 Momi S, Falcinelli E, Alberti FP, Monopoli A, Miglietta D, Ongini E, Gresele P, Abstract 15758: Anti-Inflammatory and Anti-Atherogenic Activities
of NCX 6560, a Nitric Oxide (NO)-Donating Statin, in Hypercholesterolemic Mice, Circulation 2010, 122: A15758.
3 D’Antona G, Mascarto A, Monopoli A, Miglietta D, Ongini E, Bottinelli R, Nitric oxide preserves from atorvastatin-induced skeletal muscle damage in mice. J Muscle Res Cell Motil. 2011, in press.
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