NicOx Gets Positive Phase III Naproxcinod Results
NicOx S.A. today announced that results from the first pivotal phase 3 trial for naproxcinod in patients with osteoarthritis of the knee (the 301 study) were presented on November 10, 2007 at the 71st annual meeting of the American College of Rheumatology (ACR), in Boston, Massachusetts (see NOTE). Naproxcinod is NicOx' lead investigational drug product and the first compound in the COX-Inhibiting Nitric Oxide Donator (CINOD) class. The presentation contained additional efficacy data to the top-line results announced in 2006 (see press release of October 27, 2006) which showed that naproxcinod met all three co-primary endpoints of the trial. The data showed that both doses of naproxcinod (750 mg and 375 mg bid) had superior efficacy to placebo at all time points (2, 6 and 13 weeks). This presentation also contained additional safety and tolerability information, including the gastro-intestinal adverse event rates and blood pressure measurements reported for each of the treatment groups.
Detailed clinical data from the 301 study were presented, including data for each of the three co-primary efficacy endpoints: WOMACTM pain subscale, WOMACTM function subscale and patients' overall rating of disease status. Each of the active treatments (naproxcinod 750 mg, naproxcinod 375 mg and naproxen 500 mg bid) were statistically significantly superior to placebo (p < < > =0.0002) at 2, 6 and 13 weeks. In addition, standard quality of life scores showed a functional improvement for both naproxcinod doses, as well as for the naproxen group.
At week 13, both doses of naproxcinod (750 mg and 375 mg bid) showed a slight decrease in systolic blood pressure in terms of the mean change from baseline compared to placebo (0.8 and 0.2 mmHg respectively), while a 2 mmHg increase was observed for naproxen compared to placebo. Patients' blood pressure was measured by a health care professional using office blood pressure measurements (OBPM) with standard equipment (i.e. a mercury sphygmomanometer or aneroid device) during each study visit.
Both doses of naproxcinod were shown to be safe and well tolerated, with 46.7% and 40.8% of patients experiencing at least one adverse event at 750 mg and 375 mg bid, respectively. In the naproxen and placebo bid groups, 56.4% and 38.7% of patients experienced at least one adverse event respectively. In terms of gastro-intestinal adverse events, the naproxcinod 750 mg and 375 mg bid treatment groups reported event rates of 17.0% and 12.9% respectively and the naproxen and placebo bid groups reported event rates of 23.6% and 12.2% respectively. The number of serious adverse events was low and evenly spread among the treatment groups.
"I am very pleased to be presenting these phase 3 data for naproxcinod at the ACR meeting, which is considered to be one of the leading events for the scientific and medical community in rheumatology", declared Thomas J. Schnitzer, MD, PhD, Professor of Medicine at Northwestern University Feinberg School of Medicine, Principal Investigator on the 301 study. "Naproxcinod exerts its therapeutic effect through the well-described inhibition of the cyclo-oxygenase system and a sustained donation of nitric oxide. In this clinical setting, nitric oxide may exert a protective effect in the gastro-intestinal tract and play a homeostatic role in blood pressure control. These phase 3 results suggest that naproxcinod may offer a promising clinical and pharmacological profile for the treatment of the signs and symptoms of osteoarthritis. These findings will need to be confirmed by the ongoing 302 and 303 studies."
Details of the 301 study design and patient characteristics
A total of 918 patients were randomized at 120 clinical sites in the United States to receive either naproxcinod 375 mg bid, naproxcinod 750 mg bid, naproxen 500 mg bid or placebo bid for 13 weeks. Eligible patients were at least 40 years old, with a clinical diagnosis of primary osteoarthritis of the knee of at least 3 months duration, confirmed by radiographs, and diagnosed according to the ACR guidelines (patients must qualify as ACR global functional status I, II or III). Eligible patients were also current users of Non-Steroidal Anti-inflammatory Drugs (NSAIDs) or acetaminophen (paracetamol) for their osteoarthritis pain and these analgesics were withdrawn before treatment with study-drug. The study enrolled both hypertensive and non-hypertensive patients (50.3% of enrolled patients were hypertensive at baseline). There were no statistically significant differences among the four treatment groups for any baseline variables, including hypertension medical history.
Naproxcinod is in phase 3 clinical development for the treatment of the signs and symptoms of osteoarthritis. Two remaining pivotal phase 3 trials for naproxcinod (the 302 and 303 studies) are currently ongoing and efficacy results are expected to be reported in mid-2008. The Company will conduct a statistical analysis according to a predefined plan 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: Within the framework of the ACR annual meeting held in Boston from November 6 to 11, 2007, NicOx had a corporate booth to introduce the Company and its technology to the scientific and medical community in the United-States.
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 Euronextâ„¢ 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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