October 27, 2006. Sophia Antipolis, France. www.nicox.com
NicOx S.A. (Eurolist: NICOX) today announced successful top-line results from a phase 3 trial for naproxcinod (HCT 3012) in patients with osteoarthritis of the knee (the 301 study). Both doses of naproxcinod (750 mg and 375 mg bid) were shown to be superior to placebo on all three co-primary efficacy endpoints of the study, with these results being highly statistically significant (p < 0.001). Blood pressure data for both naproxcinod doses showed a sustained reduction versus baseline and naproxen, at all time points, confirming earlier published clinical data. Naproxcinod is the first compound in the COX-Inhibiting Nitric Oxide-Donating (CINOD) class, which NicOx aims to establish as the drug-of-choice for the treatment of osteoarthritis.
"The positive outcome of this pivotal trial for naproxcinod is an important step towards making this an efficacious and potentially safer treatment option for osteoarthritis patients," said Thomas J. Schnitzer, MD, PhD, Professor and Assistant Dean for Clinical Research at Northwestern University and Principal Investigator on the trial. "The blood pressure data showing a clear improvement against naproxen and from baseline is also extremely encouraging, in the light of the considerable need for a non-steroidal anti-inflammatory drug with an improved blood pressure profile."
In terms of the co-primary endpoints of the study, both of the naproxcinod doses (375 mg bid and 750 mg bid) were shown to be superior to placebo, with this being highly statistically significant in terms of the mean change from baseline at week-13 in the following scores: the WOMAC(TM) pain subscale, the WOMAC(TM) function subscale and patients' overall rating of disease status. Superiority comparisons vs. placebo on these three co-primary endpoints conforms with FDA guidance for demonstrating the efficacy of new drugs for treating the signs and symptoms of osteoarthritis.
During the trial, patients' blood pressure was measured using office blood pressure measurements (OBPM) at each visit. Pre-specified analyses of the difference between the blood pressure at baseline and the measurements at week 2, 6 and 13, demonstrated that both naproxcinod 750 mg bid and 375 mg bid decreased systolic and diastolic blood pressure. This effect was sustained until the 13-week time point and clearly differentiated naproxcinod from naproxen.
Naproxcinod showed good overall safety; 46.7% of the patients treated with naproxcinod 750 mg bid and 40.8% on naproxcinod 375 mg bid experienced at least one adverse event, compared to 56.4% on naproxen 500 mg bid and 38.7% on placebo. The number of serious adverse events was low and evenly spread among treatment groups. The number of adverse hypotensive events was low across all groups.
Michele Garufi, Chairman and CEO of NicOx, commented: "We are extremely pleased with the top-line results from this phase 3 trial of naproxcinod which have shown unequivocal efficacy and good safety and tolerability. Additionally, these data have considerably increased our confidence that we can establish naproxcinod's non-detrimental blood pressure effect, which will be a key factor in building a blockbuster profile for naproxcinod."
NOTE 1: The 301 study is the first of three phase 3 trials in NicOx global registration plan for naproxcinod. This study is a 13-week, double-blind, placebo and naproxen-controlled trial, in patients with osteoarthritis of the knee. Eligible patients were randomized to one of four treatment groups: naproxcinod 375 mg bid, naproxcinod 750 mg bid, naproxen 500 mg bid or placebo bid, with approximately 230 patients enrolled per treatment group. Naproxcinod and placebo will be compared on three co-primary endpoints, based on the mean change between baseline and week-13 in the following scores: the WOMAC(TM) pain subscale, the WOMAC function subscale and patients' overall rating of disease status, which are the standard end-points used to demonstrate the efficacy of a drug for treating the signs and symptoms of osteoarthritis. A non-inferiority comparison of naproxcinod and naproxen will be a secondary endpoint of the study.
Office blood pressure measurements (OBPM) were performed at each visit. The key blood pressure endpoint will be based on the difference between the systolic blood pressure measurements at baseline and the mean of the measurements at week 2, 6 and 13 in the overall patient population. A number of additional endpoints will compare the blood pressure effect of naproxcinod to naproxen and placebo, in the overall population and the subpopulation of patients with hypertension, in addition to the number of patients who need to initiate, switch or increase the dose of their antihypertensive medication.
The 301 trial is expected to be followed by the initiation of two additional studies in knee and hip osteoarthritis during 2007 (the 302 and 303 studies). These studies are designed to confirm that naproxcinod is as effective as existing anti-inflammatory agents in treating the signs and symptoms of osteoarthritis. In addition to confirming the efficacy of naproxcinod, the phase 3 program is designed to show it has no detrimental effect on blood pressure, in contrast to existing anti-inflammatory agents. Patients' blood pressure is being assessed during each of the phase 3 trials using controlled office blood pressure measurements (OBPMs) during each visit to the treatment center. NicOx plans to conduct a predefined statistical analysis on the pooled OBPM data from the three studies following the completion of the last 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.
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