SOPHIA ANTIPOLIS, France, December 19 NicOxS.A. (Euronext Paris: COX) today announced positive results from the 112clinical pharmacology study in 299 patients with osteoarthritis (OA) andhypertension, which was designed to characterize the 24-hour blood pressureprofile of naproxcinod in comparison to the two most widely usednon-steroidal anti-inflammatory drugs (NSAIDs). At week 13, naproxcinod 750mg bid showed a reduction in systolic blood pressure (SBP) of 2.7 mmHgcompared to naproxen 500 mg bid and 3.8 mmHg compared to ibuprofen 600 mgtid, in the ABPM compliant population. Naproxcinod 375 mg bid showed areduction in SBP of 1.1 mmHg compared to naproxen 250 mg bid and 4.2 mmHgcompared to ibuprofen 600 mg tid.
Naproxcinod is the most advanced compound in the newCyclooxygenase-Inhibiting Nitric Oxide Donator (CINOD) class. COX-2inhibitors and traditional NSAIDs, such as ibuprofen and naproxen, are widelyused as symptomatic treatments for OA. However, there is increasing concernin the medical community over their tendency to raise blood pressure anddestabilize previously controlled hypertensive patients.
William B. White, MD, Professor of Medicine in the Cardiology Center atthe University of Connecticut School of Medicine, Farmington, commented: "Therisks of developing hypertension in patients with OA and the potential fordestabilizing blood pressure control in treated hypertensive patients whoreceive NSAID therapy are of substantial clinical concern. A new drug for thetreatment of OA which is less likely to increase blood pressure would be auseful and welcome therapy for OA patients, particularly those withhypertension."
"The results from the 112 study demonstrate important differentialeffects of naproxcinod's 24-hour ABPM profile at 13 weeks, compared toibuprofen and naproxen, two of the most commonly used NSAIDs," continuedProfessor White. "Both cardiovascular specialists and rheumatologists placegreat importance on the additional level of detail provided by the ABPMtechnique, a method which has become a gold standard in blood pressuremeasurement in clinical trials and practice. Furthermore, these new resultsshould provide support to the findings from the pooled blood pressure datafrom the phase 3 program."
Naproxcinod showed positive efficacy results in a program of threepivotal phase 3 studies in OA patients (301, 302 and 303). Moreover, apre-specified pooled analysis of the Office Blood Pressure Measurements(OBPMs) collected in 2,734 patients in these trials showed a significantreduction in SBP and diastolic blood pressure (DBP) for both doses ofnaproxcinod (375 and 750 mg bid) over the whole 13 week period, compared tonaproxen 500 mg bid. NicOx plans to submit a New Drug Application (NDA) fornaproxcinod to the US Food and Drug Administration (FDA) in mid-2009.
Both doses of naproxcinod showed a blood pressure reduction compared tonaproxen and ibuprofen.
The 112 study was a 16-week clinical pharmacology trial, with adouble-blind, parallel group design, in which 299 OA patients with controlledhypertension were enrolled at 60 clinical sites in the United States (seeNOTE 1). Patients were randomized to receive naproxcinod 375 mg bid,naproxcinod 750 mg bid, naproxen 250 mg bid, naproxen 500 mg bid, oribuprofen 600 mg tid (three times daily) for 13 weeks. The study was notdesigned to show statistical significance between the treatment arms butrather aimed to explore the 24-hour blood pressure profile of the twonaproxcinod doses, in comparison to different NSAIDs. No formal sample sizecomputations were performed in the 112 protocol.
The 24-hour blood pressure monitoring was conducted at baseline and atweek 13 using a validated ABPM device. The primary parameter was the mean24-hour ambulatory SBP as measured by ABPM at week 13. Compared to naproxen500 mg bid, naproxcinod 750 mg bid lowered SBP by 2.7 mmHg and DBP by 1.4mmHg, in terms of the mean change from baseline at week 13. Naproxcinod 375mg bid decreased SBP by 1.1 mmHg and DBP by 0.8 mmHg compared to naproxen 250mg bid.
Naproxcinod 750 mg bid showed a 3.8 mmHg decrease in SBP and a 0.7 mmHgdecrease in DBP compared to ibuprofen 600 mg tid, in terms of the mean changefrom baseline at week 13. Naproxcinod 375 mg bid showed a reduction in SBP of4.2 mmHg and a reduction in DBP of 1.7 mmHg, compared to ibuprofen 600 mg tid.
Naproxcinod 375 mg bid was the treatment with the lowest percentage ofpatients experiencing at least one adverse event. There were notreatment-related serious adverse events in the study. Far more patients inthe ibuprofen arm discontinued due to an adverse event compared to the othertreatments.
The 112 results were consistent with those of previous studies andcomplete an extensive database describing naproxcinod's differentiated bloodpressure profile.
The 112 study is the last in a program of three clinical pharmacologytrials using the ABPM technique in a total of 548 subjects (see NOTE 2 on the111 and 104 studies) and its results complete a detailed picture ofnaproxcinod's 24-hour blood pressure profile. In particular, the 112 resultscomplement and confirm the recently reported data from the 111 study, as the112 study tested corresponding doses of naproxcinod and naproxen in parallelgroups, while the 111 study tested escalating doses of naproxcinod andnaproxen. The extensive blood pressure data from these three ABPM studiessuggest an effect of nitric oxide donation on blood pressure.
Further analyses on the 111 and 112 studies will form the basis ofpresentations at leading medical conferences and peer reviewed scientificpublications during 2009 and 2010.
Pascal Pfister MD, Chief Scientific Officer and Head of Research andDevelopment at NicOx, said: "With these results we have successfullyfinalized our extensive program of clinical studies specifically designed tocharacterize the blood pressure profile of naproxcinod. The 112 resultscomplete a positive and consistent package of OBPM and ABPM data in over3,000 patients. We have great confidence in this robust clinical databasewhich shows naproxcinod's differentiated blood pressure profile across thedose range and at multiple time points up to 26 weeks."
NOTE 1: In the 112 study, eligible patients were 40 years and older andhad been suffering from osteoarthritis for at least three months, with atleast one hip or knee involved. In addition to OA, all patients werediagnosed with controlled essential hypertension (i.e. systolic bloodpressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg) andwere treated with stable doses of up to two different classes ofantihypertensive agents. Patients with uncontrolled hypertension wereexcluded.
NOTE 2: In the 111 ABPM study, 118 OA patients with controlledhypertension were randomized on a 1:1 basis to receive naproxcinod ornaproxen, with escalating doses every three weeks (375, 750 and asupra-therapeutic dose of 1125 mg bid for naproxcinod; 250, 500 and 750 mgbid for naproxen). Naproxcinod showed a statistically significant decrease inSBP of 3.8 mmHg (p=0.011) compared to naproxen over the whole study period.The 104 trial was a cross-over ABPM study in 131 hypertensive volunteers,which was designed to compare the 24-hour blood pressure profiles ofnaproxcinod 750 mg bid and naproxen 500 mg bid following two weeks ofadministration.
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 ofrisks and uncertainties which could cause actual results, financialcondition, performance or achievements of NicOx S.A. to differ from thosecontained in the forward-looking statements, please refer to the Risk Factors("Facteurs de Risque") section of the Document de Reference filed with theAMF, which is available on the AMF website ( http://www.amf-france.org) or onNicOx S.A.'s website (http://www.nicox.com).