PARIS, September 15 /PRNewswire-FirstCall/ -- NicOx S.A. (Euronext Paris: COX) today announced successful top-line results from the second phase 3 study for naproxcinod in 1020 patients with osteoarthritis of the knee (the 302 study). Both doses of naproxcinod (750 mg and 375 mg bid) met the three co-primary efficacy endpoints at week-13 (p<0.001). The study also comfortably met the main secondary endpoint, demonstrating that naproxcinod 750 mg bid was statistically non-inferior to naproxen 500 mg bid on the WOMAC(TM) pain and function subscales at week-13 and 26. Naproxcinod is the first compound in the new Cyclooxygenase-Inhibiting Nitric Oxide-Donator (CINOD) class of anti-inflammatory agents, which NicOx is developing as a drug for the treatment of the signs and symptoms of osteoarthritis.
NicOx' phase 3 clinical program for naproxcinod consists of three pivotal trials (including the previously completed 301 study in osteoarthritis of the knee and the ongoing 303 study in osteoarthritis of the hip, in addition to the 302 study). Overall, the results of the 302 study support naproxcinod's non-detrimental effect on blood pressure and are consistent with those observed in the 301 study, with naproxcinod 750 mg bid showing a numerical reduction in systolic and diastolic blood pressure at week-13 and 26, compared to baseline and naproxen 500 mg bid. Existing non-steroidal anti-inflammatory agents (NSAIDs) such as ibuprofen and naproxen have the tendency to raise blood pressure, which is a side effect of particular concern in the osteoarthritis population.
A post hoc pooled analysis of the blood pressure data from the 301 and 302 studies showed a statistically significant reduction for naproxcinod 750 mg bid, compared to naproxen 500 mg bid, in terms of the mean change from baseline at week-13, of 2.3 mmHg (p=0.004) for systolic blood pressure and 1.1 mmHg (p=0.034) for diastolic blood pressure. In the planning of the phase 3 program, NicOx had foreseen the pooling of office blood pressure measurements (OBPMs) from more than one study in order to obtain the necessary statistical power to correctly assess the effects of naproxcinod on blood pressure, compared to naproxen. A pre-specified analysis of the pooled blood pressure data from the three phase 3 studies will be conducted following the completion of the third phase 3 trial (the 303 study) in the fourth quarter of 2008.
Michele Garufi, Chairman and CEO of NicOx, commented: "We are impressed by the strong efficacy results observed in this study, which have replicated the positive results of the 301 trial and clearly demonstrated non-inferiority to naproxen at 26 weeks. The results of these two pivotal studies give us increasing confidence that naproxcinod will meet regulatory requirements for approval in the United States and Europe. Moreover, based on the results of the pooled analysis on blood pressure from these studies, we firmly believe that naproxcinod has the potential to fulfill the current medical need for an efficacious anti-inflammatory agent with no detrimental impact on blood pressure."
Positive efficacy results in comparison to placebo and naproxen
As in the 301 study, both naproxcinod doses (375 mg bid and 750 mg bid) were shown to be superior to placebo on the three co-primary efficacy endpoints of the 302 trial, the WOMAC(TM) pain subscale, the WOMAC(TM) function subscale and patients' overall rating of disease status, with these being highly statistically significant (p<0.001) in terms of the mean change from baseline at week-13. Superiority comparisons versus placebo on these three co-primary endpoints in two well designed, well controlled trials conform to U.S. Food and Drug Administration (FDA) guidance for demonstrating the efficacy of new drugs for the treatment of the signs and symptoms of osteoarthritis.
The main secondary endpoint of the trial assessed the efficacy of naproxcinod 750 mg bid to naproxen 500 mg bid at week-13 and 26 in terms of the mean change from baseline in the WOMAC(TM) pain and function subscales. Naproxcinod 750 mg bid comfortably met the secondary endpoint of being statistically non-inferior to naproxen 500 mg bid on these two parameters. Although not a pre-specified secondary endpoint of the study, a post hoc analysis showed that naproxcinod 375 mg bid was also statistically non-inferior to naproxen 500 mg bid at week-26 on these two parameters. Non-inferiority comparisons to existing products are required by the European Medicines Agency (EMEA) for demonstrating the efficacy of new drugs.
Results support favorable blood pressure profile versus naproxen
During the trial, patients' blood pressure was measured using office blood pressure measurements (OBPM) at each visit to the clinical center, using a standardized, well controlled approach. A pre-specified analysis compared naproxcinod to naproxen, in terms of the mean change from baseline in systolic and diastolic blood pressure at baseline and weeks-2, 6, 13, 15 and 26. The results support naproxcinod's non-detrimental effect on blood pressure and are consistent with those observed in the 301 study with both doses of naproxcinod showing a numerical reduction in systolic and diastolic blood pressure, compared to baseline and naproxen 500 mg bid, which was sustained over the vast majority of the time points.
No safety concerns up to week-26
There were no safety concerns relating to naproxcinod treatment up to week-26 and all the active treatment arms were similar to placebo in terms of the percentage of patients with one or more adverse event at week-13. At week-26, the percentage of patients with one or more adverse event was similar for each of the study drugs. The number of serious adverse events was low and evenly distributed among the treatment groups.
NOTE: NicOx entered into a full-service agreement for the conduct of the 302 study with Premier Research Group Limited, a global CRO specializing in the conduct of clinical trials in pain indications and other important therapeutic areas. The study is a 53-week, randomized, double-blind, efficacy and safety trial in which 1020 patients with osteoarthritis of the knee were enrolled at around 150 clinical sites throughout the United States. Patients were randomized to one of the following treatment groups: naproxcinod 375 mg bid (52 weeks), naproxcinod 750 mg bid (52 weeks), naproxen 500 mg bid (52 weeks) and placebo bid during the first 13 weeks. After week-13, the placebo treated patients were randomized in a blinded fashion to either naproxcinod 375 mg bid or naproxcinod 750 mg bid for the remainder of the trial (39 weeks). Patients had primary osteoarthritis of the knee of at least 3 months duration. The general safety and tolerability of naproxcinod are still being assessed until week-52 and the trial has a 1 week post-treatment safety period. For further details of the 302 study design, see the NicOx press release of April 3, 2007.
NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-driven biopharmaceutical company dedicated to the development and future commercialization of investigational drugs for unmet medical needs. NicOx is applying its proprietary nitric oxide-donating technology to develop an internal portfolio of New Chemical Entities (NCEs) in the therapeutic areas of inflammatory and cardio-metabolic disease.
Resources are focused on the development of naproxcinod, a proprietary NCE and the first compound in the Cyclooxygenase-Inhibiting Nitric Oxide-Donator (CINOD) class of anti-inflammatory agents, which is in phase 3 clinical studies for the treatment of the signs and symptoms of osteoarthritis, with final phase 3 results anticipated in 2008.
Beyond naproxcinod, NicOx has a pipeline containing multiple nitric oxide-donating NCEs, which are in development internally and with partners, including Pfizer Inc. and Merck & Co., Inc., for the treatment of prevalent and underserved diseases, such as atherosclerosis, hypertension, widespread eye diseases and Chronic Obstructive Pulmonary Disease (COPD).
NicOx S.A. is headquartered in France and is listed on the Euronext Paris Stock Exchange (Compartment B: Mid Caps).
This press release contains certain forward-looking statements. Although the Company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated in the forward-looking statements.
For a discussion of risks and uncertainties which could cause actual results, financial condition, performance or achievements of NicOx S.A. to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference filed with the AMF, which is available on the AMF website ( http://www.amf-france.org) or on NicOx S.A.'s website (http://www.nicox.com).
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