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Following the positive results from the 301 and 302 studies in patientswith OA of the knee, 303 represents the third phase 3 study for naproxcinodto achieve p<0.001 on all three co-primary efficacy endpoints. The 303 studyis also the final pivotal trial that NicOx plans to include in the submissionof a New Drug Application (NDA) to the US Food and Drug Administration (FDA)in mid-2009.
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"This study has demonstrated clear-cut efficacy for naproxcinod 750 mgbid in hip OA, in addition to providing reassuring blood pressure and safetydata," said Thomas J. Schnitzer, MD, PhD, Professor of Medicine atNorthwestern University Feinberg School of Medicine, who advised NicOx on thedesign and analysis of the trial. "Meeting the primary endpoints of thisstudy is a significant achievement, considering the difficultly incontrolling the symptoms of hip OA patients. Few studies with otheranti-inflammatory agents have focused only on people with hip OA, in partbecause of the increased difficulty in demonstrating efficacy in thispopulation compared to knee OA. Additionally, the fact that the bloodpressure data for naproxcinod and placebo were similar at all time points isalso encouraging, as there is a definite need for new anti-inflammatoryagents that do not increase blood pressure."
Results clearly support naproxcinod's non-detrimental blood pressureprofile
The blood pressure data for naproxcinod 750 mg bid were consistent withthose obtained in the 301 and 302 studies. Blood pressure was measured usingstandardized and controlled office blood pressure measurements (OBPM) atbaseline and at weeks 2, 6 and 13 (see NOTE). At all time points, thepatients treated with naproxcinod 750 mg bid showed a very similar bloodpressure profile to those on placebo. In addition, naproxcinod 750 mg bidshowed a clear reduction in systolic and diastolic blood pressure (SBP andDBP) compared to naproxen 500 mg bid at all time points. No stand alonestatistical analysis of the blood pressure data from the 303 study waspre-specified.
As planned, NicOx will pool the blood pressure data from the three phase3 studies (301, 302 and 303) according to a prospectively designed protocolthat has been submitted to the FDA. The Company will disclose the top-lineresults of the pre-specified statistical analysis on the pooled data in thecoming weeks.
Naproxcinod and placebo show the same gastrointestinal (GI) adverse eventrate
Naproxcinod 750 mg bid showed good overall safety and tolerability. Thepercentage of patients who experienced one or more GI adverse events was thesame for placebo and naproxcinod 750 mg bid at 15.5%, compared to 19.2% fornaproxen 500 mg bid. In terms of the percentage of patients who experiencedat least one adverse event overall, this was lower for naproxcinod 750 mgthan naproxen 500 mg bid. There was not a single serious cardiovascular orserious GI adverse event in the naproxcinod arm during the 13 weeks of the303 study, in contrast to the placebo and naproxen 500 mg bid arms.
Pascal Pfister MD, Chief Scientific Officer and Head of Research andDevelopment at NicOx, commented: "We believe these are extremely goodresults, with naproxcinod demonstrating clear efficacy in this difficult typeof osteoarthritis patients and showing the same GI adverse event rate asplacebo. The blood pressure data are consistent with previous studies and weare keenly awaiting the important results of the pre-defined statisticalanalysis in the next few weeks, following the pooling of the 301, 302 and 303blood pressure data. We are confident that these results will clearlydemonstrate naproxcinod's non-detrimental blood pressure profile, in contrastto naproxen."
Design and results of the 303 study
The 303 study was a 13-week, double-blind, placebo and naproxencontrolled trial in patients with OA of the hip. 810 patients were enrolledat 120 clinical centers in the United States, Canada and Europe. Eligiblepatients had a diagnosis of primary osteoarthritis of the hip of at leastthree months in duration and were randomized on a 2:2:1 basis to receivenaproxcinod 750 mg bid, placebo bid and naproxen 500 mg bid, respectively.
The three co-primary endpoints of the study compared the efficacy ofnaproxcinod 750 mg bid to placebo, in terms of the mean change betweenbaseline and week 13 in the following scores: the WOMAC(TM) pain subscale,the WOMAC(TM) function subscale and the subject's overall rating of diseasestatus. The results demonstrated that naproxcinod was superior to placebowith high statistical significance (p<0.001) on all three of these co-primaryendpoints. These were the same endpoints as those used in the 301 and 302phase 3 studies. No statistical comparison was made between naproxen 500 mgbid and the other two arms on the efficacy endpoints, due to the 2:2:1randomization in the study, although numerical data show that naproxcinod 750mg bid behaved in a similar fashion to naproxen 500 mg bid on these efficacyscores. NicOx entered into a full-service agreement for the conduct of the303 study with Covance Inc., a global contract research organization (CRO).
NOTE: Office Blood Pressure Measurements (OBPMs) were performed by ahealth care professional during a patient's visit to the treatment centerusing a standard technique and equipment (i.e. a sphygmomanometer). OBPMswere performed in the morning and the time between intake of study-drug andmeasurement of OBPM was between 2 and 4 hours.
NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-drivenbiopharmaceutical company dedicated to the development and futurecommercialization of investigational drugs for unmet medical needs. NicOx isapplying its proprietary nitric oxide-donating technology to develop aninternal portfolio of New Chemical Entities (NCEs) in the therapeutic areasof inflammatory and cardio-metabolic disease.
Resources are focused on the development and pre-commercializationactivities for naproxcinod, a proprietary NCE and the first compound in theCyclooxygenase-Inhibiting Nitric Oxide-Donating (CINOD) class ofanti-inflammatory agents for the treatment of the signs and symptoms ofosteoarthritis. Naproxcinod has completed three pivotal phase 3 studies withpositive results and the submission of a New Drug Application (NDA) to the USFood and Drug Administration (FDA) is projected for mid-2009.
Beyond naproxcinod, NicOx has a pipeline containing multiple nitricoxide-donating NCEs, which are in development internally and with partners,including Pfizer Inc and Merck & Co., Inc., for the treatment of prevalentand underserved diseases, such as atherosclerosis, hypertension, widespreadeye diseases and Chronic Obstructive Pulmonary Disease (COPD).
NicOx S.A. is headquartered in France and is listed on the NYSE EuronextParis (Compartment B: Mid Caps).
This press release contains certain forward-looking statements. Althoughthe Company believes its expectations are based on reasonable assumptions,these forward-looking statements are subject to numerous risks anduncertainties, which could cause actual results to differ materially fromthose anticipated in the forward-looking statements.
For a discussion of risks and uncertainties which could cause actualresults, financial condition, performance or achievements of NicOx S.A. todiffer from those contained in the forward-looking statements, please referto the Risk Factors ("Facteurs de Risque") section of the Document deReference 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).
http://www.nicox.com
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