NicOx 4016 / PAOD PIIA results
NCX 4016 Successfully Achieves Primary Efficacy Endpoint In Phase II Clinical Study of Symptomatic Peripheral Arterial Obstructive Disease (PAOD)
Thursday January 8, 1:00 am ET
SOPHIA ANTIPOLIS, France, Jan. 8 /PRNewswire-FirstCall/ -- NicOx SA (Nouveau Marche: NICOX) announces today that NCX 4016 reached its primary efficacy endpoint in a Phase IIa study in patients with symptomatic peripheral arterial obstructive disease (PAOD - see note 1). NCX 4016 is a novel nitric oxide-donating derivative of aspirin in development for the prevention and treatment of cardiovascular diseases.
This Phase IIa clinical study, conducted in Italy by Paolo Gresele, Professor at the University of Perugia, involved 44 PAOD patients, diagnosed with Fontaine Stage II, with limitations in walking capacity due to leg pain (claudicatio intermittens). Patients were treated for 1 month with either NCX 4016 (800 mg bid) or aspirin (100 mg od). At the end of the study, NCX 4016 showed statistical significance on the primary endpoint of the study which was to reverse endothelium dysfunction induced by physical exercise as measured by flow mediated vasodilation (FMD - see note 2) (p= 0.036). In contrast, aspirin had no effect (p = 0.038 vs. aspirin).
Walking capacity, a secondary parameter defined by Initial Claudication Distance (ICD) was evaluated by a standard treadmill exercise test (see note 3) and showed a clinically meaningful increase with NCX 4016 compared to aspirin. Furthermore, the safety and overall tolerability of NCX 4016 were excellent.
Endothelial dysfunction, which results in abnormal vessel functioning and which correlates to atherosclerosis development and long-term cardiovascular risk, is a hallmark of generalized chronic arterial diseases and is well known to be related to nitric oxide-dependent pathways. It is known that therapies that enhance nitric oxide-dependent pathways and that are effective in secondary prevention of cardiovascular events also improve endothelial function. These results suggest that the observed beneficial effects of NCX 4016 on vasculature are likely to be due to nitric oxide donation.
The rationale for development of NCX 4016 in PAOD is based on data from preclinical and Phase I studies involving more than 300 subjects. These data showed that NCX 4016 has a broad range of vascular anti-inflammatory and anti- thrombotic activity acting on multiple targets in the ischemia-reperfusion pathway, coupled with excellent GI and overall safety.
Michele Garufi, Chairman and CEO of NicOx, commented: "The results of this first Phase II study in PAOD provide strong evidence of clinical activity and support the rationale for further development of NCX 4016. As such, PAOD is an attractive first indication in which NicOx intends to pursue a regulatory filing, currently anticipated in 2007. Such a strategy is in line with the Company's focus of resources on the most advanced products in our clinical pipeline. Furthermore these data support the hypothesis that NCX 4016 may be effective in improving endothelium dysfunction by virtue of its nitric oxide- donation creating the potential for the product's future development in a broad range of endothelium dysfunction-related disorders, which we plan to explore in an expanded Phase II programme."
NicOx and Paolo Gresele, Professor of Internal Medicine at the University of Perugia and Principal Investigator for the study, will host a conference call today at 12:00 CET / 11:00 GMT. Accompanying slides will be available on NicOx' web site at www.nicox.com. Please contact Claire Rowell at Financial Dynamics on +44 (0)207 269 7285 for the call in details.
NOTE TO EDITORS:
NOTE (1)
PAOD is due to atherosclerosis of the arteries that supply the lower limbs and affects a significant portion of the overall population. The prevalence of PAOD is increasing with the aging population. It is estimated that more than 14 million subjects are diagnosed with PAOD in the USA and Western Europe. Chronic PAOD is a marker of widespread atherosclerosis, and patients with intermittent claudication must be considered a high-risk population for the development of clinical manifestations of cardiovascular diseases. The principal symptom of PAOD is leg pain during walking (intermittent claudication) due to a reduction of blood flow in lower limb arteries determining cyclic episodes of ischemia during walking followed by reperfusion during rest. This results in platelet and leukocyte activation, microcirculatory impairment and endothelial dysfunction.
The therapeutic goals for the treatment of patients with PAOD, aside pharmacological and general measures to reduce the cardiovascular risk, are to relieve symptoms, primarily to improve walking capacity. Current therapies are few and are limited by modest efficacy and/or significant tolerability issues. Currently, the PAOD market is devoid of therapies that provide effective symptomatic relief in patients with early stage disease and offers few options apart from surgery to patients in the advanced stage of the disease. There is a growing need for new drugs that are both effective in the relief of symptoms and in the secondary prevention of cardiovascular events.
NOTE (2)
The primary endpoint of the study was flow mediated dilation (FMD) measured with a high frequency ultrasound technique at a prespecified point of the brachial artery. Flow mediated dilation actually measures the capacity of arterial vessels to dilate (and hence to increase blood flow) as response to standardized ischemia. The principle is that normal vessels are able to significantly dilate after ischemia to allow the restoration of normal metabolic conditions by providing an increased supply of oxygenated blood to the ischemic area. This event is strictly dependent upon preservation of nitric oxide pathways. Chronic arterial diseases are characterized by impairment of synthesis of nitric oxide from endothelium and by impaired dilation of arterial vessels following the ischemic stimulus. Recent papers show that this non invasive method to evaluate endothelial function is a strong independent predictor of long term cardiovascular risk in patients with PAOD and correlates with the presence of angiographically proven coronary artery disease.(Gokce N, Circulation 2002: 105: 1567-72; Gokce N, JACC 2003;41:1769-75; Brevetti G., Circulation 2003;108:2093-2098 ; Lieberman EH, Am J Cardiol 1996;78:1210-4 ; Corretti MC, JACC 2002;39:257-65; Faulx MD, Am Heart J 2003;145:943-51
NOTE (3)
Standard treadmill exercise protocol (3km/hr at 10 degree incline). Patients who were entered into the trial had ischemic pain before 10 minutes of standard treadmill exercise at the screening test (day -15).
NicOx S.A.(Bloomberg: NICXF, Reuters: NCOX.LN), headquartered in Sophia- Antipolis, France, is a Public company listed on the Nouveau Marche of Euronext Paris (segment: Next Economy). NicOx is targeting several major pharmaceutical markets including pain and inflammation, cardiovascular diseases, respiratory disorders, inflammatory bowel diseases, urinary incontinence, osteoporosis, certain dermatological disorders, certain liver diseases, Alzheimer's disease and colon cancer. |
