Press Release: Results for NicOx's ABPM Trial

NicOx ABPM Trial Shows Favorable Blood Pressure Profile For Naproxcinod; Drug Misses Study Goal SOPHIA-ANTIPOLIS, France, Dec. 8 /PRNewswire-FirstCall/ -- NicOx S.A. (Eurolist: NICOX) today announced top-line results from a pharmacodynamic clinical study utilizing Ambulatory Blood Pressure Monitoring (ABPM), which demonstrated a differentiated and favorable 24 hour blood pressure profile for naproxcinod, compared to naproxen, in hypertensive subjects after two weeks. The trial results showed a 2 mmHg difference in both the average systolic and diastolic blood pressure in favor of naproxcinod, in terms of the mean change from baseline as measured by ABPM. This difference did not reach statistical significance for systolic blood pressure, the primary endpoint of the trial (p=0.101). However statistical significance was achieved for diastolic blood pressure, which was an important secondary endpoint (p=0.007). Naproxcinod is a proprietary, first in class, COX-Inhibiting Nitric Oxide-Donator (CINOD), which is currently in phase 3 clinical development for the treatment of the signs and symptoms of osteoarthritis. The magnitude of the blood pressure differentiation seen for naproxcinod in this ABPM trial is consistent with that observed after 2 weeks in the recently announced successful pivotal phase 3 efficacy trial in osteoarthritis patients (301 study, see press release of October 27, 2006). The Office Blood Pressure Measurements (OBPM) collected in the 301 trial showed a reduction in systolic and diastolic blood pressure versus baseline and naproxen, which was sustained over the full 13 weeks of the study, although the maximal difference for systolic blood pressure was only reached at the 6 and 13 week time points. The results announced today were from a non-pivotal, exploratory, pharmacodynamic study, which was designed to provide complementary blood pressure data to the phase 3 program by using an ABPM device (see NOTE 1) to assess the 24 hour blood pressure profile of naproxcinod and naproxen in stable hypertensive subjects at 2 weeks. "We are encouraged that this study has shown a clear and positive differentiation in the blood pressure curves for naproxcinod compared to naproxen when viewed over 24 hours," said Maarten Beekman, Vice President of Clinical Development at NicOx. "These results are in line with the difference in systolic and diastolic blood pressure that we observed for naproxcinod at two weeks in the recently announced results from the 301 phase 3 trial. We will continue to analyze the data, with a view to increasing our understanding of naproxcinod's potentially beneficial blood pressure effect." The ABPM trial was a phase 1 study, in which 131 volunteer subjects with stable essential hypertension were enrolled at 15 active clinical centers in the United States. The subjects were not osteoarthritis patients but were between 50 and 75 years old, in order to be representative of the osteoarthritis population (see NOTE 2). Subjects were randomized to one of two groups: around half were administered with 750 mg of naproxcinod, twice-daily, for 14-days, followed by 500 mg of naproxen, twice-daily, for 14 days and the other half received the compounds in the opposite order. Placebo was administered during wash-out periods. The primary endpoint of the trial was the mean change from baseline in the average systolic blood pressure recorded during a 24-hour ABPM, following a 14 day administration of naproxcinod or naproxen. On this primary endpoint, a non-statistically significant difference of 2 mmHg was observed, between naproxcinod and naproxen, although the p value of 0.101 indicates a strong trend in favor of naproxcinod. An important secondary endpoint of the trial was the mean change from baseline in the average 24-hour diastolic blood pressure at 14 days, where naproxcinod showed a 2 mmHg difference in favor of naproxcinod, which was statistically significant compared to naproxen (p=0.007). The analysis of additional secondary endpoints is currently ongoing. The number of adverse events was low across both active treatment periods. "The results of this two week trial suggest that nitric oxide donation from naproxcinod has a beneficial effect on both systolic and diastolic blood pressure," said Raymond Townsend, Professor of Medicine at the University of Pennsylvania, who advised NicOx on the design and analysis of the study. "The potential chronic effect of nitric oxide donation on systolic measurements deserves further investigation, as it may represent a long-term correction of physiological systems that control blood pressure, which are known to malfunction when nitric oxide levels are deficient." Non steroidal anti-inflammatory drugs (NSAIDs), such as naproxen, represent the major established symptomatic treatment for the millions of patients who suffer from osteoarthritis. Despite the established efficacy of these agents, they are known to raise blood pressure and interfere with the treatment of hypertension. With at least 40% of osteoarthritis patients estimated to be hypertensive, NicOx aims to demonstrate that naproxcinod has a beneficial and differentiated blood pressure profile compared to existing NSAIDs. NOTE 1: - Ambulatory blood pressure monitoring (ABPM) involves using a portable device to independently measure and record blood pressure at frequent intervals over a 24-hour period with minimal disruption of the subject's daily activity. It is known that blood pressure follows a circadian cycle which fluctuates over the day and the night and that the ABPM technique therefore provides important data regarding the overall blood pressure profile of pharmaceutical products in development. The frequency of blood pressure measurements in this study was every 20 minutes, during the day, and every hour during the night. - Office blood pressure measurements (OBPM) are made by a health care professional during a subject's visit to their treatment center using standard equipment (i.e. a sphygmomanometer). - Systolic blood pressure is the maximum pressure in the arteries when the heart is contracting, while diastolic pressure is the lowest pressure between heart beats. NOTE 2: Eligible subjects were receiving stable antihypertensive treatment at screening. This was defined as no change in the type of drug they had received, or no change in dose of 50% or more, due to disease worsening or lack of efficacy in the 3 months before screening. Antihypertensive treatment was limited to a maximum of two different classes of antihypertensive agents, at no more than their recommended dose. People with uncontrolled hypertension were excluded from the study, as were those using chronic analgesic or anti-inflammatory therapy, or which were expected to do so during the trial. 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 de reference. Source: NicOx S.A.