November 7, 2007. Sophia Antipolis, France. www.nicox.com
NicOx S.A. (Eurolist: COX) today announced that clinical results of an exploratory pharmacodynamic study for naproxcinod using Ambulatory Blood Pressure Monitoring (ABPM) were presented yesterday at the American Heart Association Scientific Sessions 2007, in Orlando, Florida. Naproxcinod is the first compound in the COX-Inhibiting Nitric Oxide Donator class of anti-inflammatory agents and is in clinical development for the treatment of the signs and symptoms of osteoarthritis. This ABPM study was designed to provide complementary blood pressure data to the ongoing phase 3 program. The data presented at the AHA showed that the blood pressure measurements for naproxcinod over 24 hours were consistently below those observed for naproxen, a currently marketed non-steroidal anti-inflammatory agent (NSAID). NSAIDs are known to have the detrimental effect of raising patients' blood pressure. The top-line results of this trial (the 104 study) were announced last December (see press release of December 8, 2006).
The presentation included line graphs displaying the hourly mean blood pressure measurements over 24 hours following a two week treatment period, during which naproxcinod or naproxen were administered twice daily. These graphs showed that the hourly systolic blood pressure (SBP) and diastolic blood pressure (DBP) values for naproxcinod were consistently below those observed in the naproxen group (see NOTE 1). In addition, the data suggest that the blood pressure effect of naproxcinod lasts for 7 to 8 hours after each administration.
Considering the average of the ABPM measurements over 24 hours the results showed an almost 2 mmHg reduction in SBP and DBP for naproxcinod compared to naproxen, in terms of the mean change from baseline, after a 2 week active treatment period. This difference did not reach statistical significance for SBP (p < > =0.101), the primary endpoint of the study, but did achieve statistical significance for DBP (p < > =0.007).
Blood pressure data were collected in the first phase 3 trial for naproxcinod (the 301 study) using Office Blood Pressure Measurements (OBPM) up to 13 weeks (see NOTE 2). The top-line results of this trial revealed a sustained reduction in blood pressure for naproxcinod, compared to baseline and naproxen. Additional results from this phase 3 trial are due to be presented on November 10, 2007, at the 71st annual meeting of the American College of Rheumatology.
"This ABPM trial was the first clinical study focusing specifically on naproxcinod's 24 hour blood pressure profile and its results reveal a clear difference compared to naproxen, which is one of the best-known cardiovascular NSAIDs", said Raymond Townsend, Professor of Medicine at the University of Pennsylvania, Philadelphia, who advised NicOx on the ABPM study. "The medical community recognizes the importance of blood pressure control in reducing the rate of serious cardiovascular events in elderly patients. These data add to the promising blood pressure results obtained by OBPM in the first 13-week phase 3 study and, if supported by the results of the ongoing 302 and 303 phase 3 studies, should contribute to naproxcinod becoming a valuable alternative to selective and non selective NSAIDs for treating the signs and symptoms of osteoarthritis".
The presentation showed naproxcinod was well tolerated during the study. The number of subjects with at least one treatment related adverse event was low and evenly spread between naproxcinod and naproxen. There were no adverse events suggesting clinically significant hypotensive effects in either group.
Details of study design and ABPM monitoring
The trial was an 8-week, double-blind, randomized, cross-over study in which 131 male and female healthy volunteers were enrolled at 15 US clinical sites to receive either naproxcinod 750 mg bid, followed by naproxen 500 mg bid for 2 weeks, or these compounds in the reverse order. Subjects received a 2 week placebo wash-out before and in between the active treatment periods. Eligible subjects were between 50 and 75 years of age, in order to be representative of the osteoarthritis population, and 71.8% were over 65 years of age. Eligible subjects had controlled hypertension, defined as SBP inferior to 150 mmHg and/or DBP inferior to 95 mmHg and were treated for their hypertension by drugs from no more than 2 different antihypertensive drug classes at stable doses at screening. Eligible patients were not current NSAID users.
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. In this trial, a 24-hour ABPM was performed at the start and following each of the two active treatment periods. During the 24-hour period, blood pressure measurements were taken at 20-minute intervals between 6:00 am and 10:00 pm and every hour from 10:01 pm to 5:59 am. In total four 24-hour ABPM measurements were taken per subject.
About naproxcinod
Naproxcinod, NicOx' lead investigational product, is in phase 3 clinical development for the treatment of the signs and symptoms of osteoarthritis. Results from the first pivotal phase 3 study (the 301 study) showed that naproxcinod has superior efficacy compared to placebo and no detrimental effect on blood pressure, in contrast to the existing anti-inflammatory agent naproxen. The two remaining pivotal phase 3 trials for naproxcinod are currently ongoing (302 and 303) and patients are undergoing standardized blood pressure measurements at each visit to the treatment center in these studies (Office Blood Pressure Measurements, OBPM). The Company expects to report the 302 and 303 efficacy results in mid-2008 and will conduct a predefined statistical analysis on the pooled OBPM data from the three phase 3 studies (301, 302 and 303), following the completion of the 302 and 303 studies. NicOx anticipates filing a New Drug Application for naproxcinod in the United-States during the first quarter of 2009.
NOTE 1: 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: 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).
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 inflammation and cardio-metabolic disease. Resources are focused on two lead compounds, naproxcinod (formerly HCT 3012); in phase 3 development for the treatment of signs and symptoms 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 & Co., Inc.
NicOx S.A. is headquartered in Sophia-Antipolis, France, and is a public company listed on the Eurolist of EuronextTM 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.
CONTACTS: http://www.nicox.com
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