SOPHIA ANTIPOLIS, France, June 13
NicOx S.A. (Euronext Paris: COX) today announced an additional analysis ofthe blood pressure data from the 301 phase 3 study, showing a statisticallysignificant difference between naproxcinod and naproxen in terms of the meanchange from baseline in systolic and diastolic blood pressure at week 13(p<0.05 for 3 out of 4 comparisons). Commonly used Non-SteroidalAnti-Inflammatory Drugs (NSAIDs), such as naproxen, have the tendency to raiseblood pressure to an extent that may increase the rate of seriouscardiovascular adverse events. The new results are being presented today atthe 2008 European League Against Rheumatism (EULAR) Congress in Paris.Naproxcinod is NicOx' lead investigational drug and the first compound in theCyclooxygenase-Inhibiting Nitric Oxide Donator (CINOD) class, which NicOx isdeveloping for the treatment of the signs and symptoms of osteoarthritis.
Positive top-line efficacy results from the 301 study have been previouslyannounced, showing that both doses of naproxcinod (750 mg and 375 mg bid) weresuperior to placebo on all three co-primary efficacy endpoints (p<0.001).Patients' blood pressure was also measured in the study, with a well definedstandardized approach where investigators took office blood pressuremeasurements (OBPM) at each patient visit to the clinical site. The OBPMchanges from baseline at week 13 were predefined safety endpoints of the studyand the statistical analysis announced today was conducted on a post hocbasis.
Pascal Pfister MD, Chief Scientific Officer and Head of Research andDevelopment at NicOx, said: "We are very pleased to be presenting theseimportant data from our most advanced CINOD at EULAR. We believe the resultsof the post hoc statistical analysis on blood pressure are particularlyencouraging, as the 301 study was not powered to show a significant differencebetween naproxcinod and naproxen on this safety endpoint. The fact thatsignificance has been observed in a single trial supports our confidence thata clear statistical differentiation will be obtained between naproxcinod andnaproxen in the predefined pooled analysis of the OBPM data."
Two remaining phase 3 trials for naproxcinod are currently ongoing (the302 and 303 studies) and their results are anticipated in the second half of2008. Naproxcinod's effect on blood pressure, in comparison to naproxen andplacebo, will also be assessed by OBPM in these trials, allowing NicOx toperform a predefined statistical analysis on the pooled OBPM data. NicOxprojects the filing of a New Drug Application (NDA) for naproxcinod inmid-2009.
Results of the blood pressure analysis
At week 13, naproxcinod showed mean changes from baseline in systolicblood pressure, compared to naproxen, of minus 2.89 mmHg (p<0.05) for the 750mg bid dose and -1.82 mmHg (p=0.12) for the 375 mg bid dose. For diastolicblood pressure, in terms of mean changes from baseline compared to naproxen,naproxcinod 750 mg bid was -1.79 mmHg (p<0.05) and naproxcinod 375 mg bid was-1.55 mmHg (p<0.05). At the week 13 time point, more individual patients onnaproxcinod showed a decrease in blood pressure compared to patients onplacebo and naproxen.
Assessment of efficacy in the trial
The presentation contains additional information on the efficacy outcomemeasures of the study, going beyond the top-line results announced in 2006(see press release of October 27, 2006). The detailed results for the twodoses of naproxcinod, naproxen and placebo on the WOMAC(TM) pain subscale,WOMAC(TM) function subscale and patients' overall rating of disease status, at2, 6 and 13 weeks are being displayed in graphical form. The three co-primaryendpoints of the study assessed these scores at 13 weeks, in comparison tobaseline. Sensitivity and subgroup analyses confirmed the positive result onthese co-primary endpoints. Additional efficacy end