SOPHIA ANTIPOLIS, France, May 6 /PRNewswire-FirstCall/ -- NicOx S.A. (Euronext Paris: COX) today announced the results of a U.S. phase 2 study, conducted by its partner Pfizer Inc, which compared the safety and efficacy of various doses of PF-03187207 to Xalatan(R) (latanoprost) 0.005% in patients with primary open-angle glaucoma and ocular hypertension. The higher doses of PF-03187207 demonstrated a clinically significant reduction in diurnal intraocular pressure (IOP) from baseline and the highest dose showed consistently more IOP lowering than Xalatan(R) 0.005%, at all study visits and at all individual time points, suggesting a beneficial effect of nitric oxide donation. PF-03187207 is a nitric oxide-donating prostaglandin analog, which is covered by the companies' August 2004 agreement.
On the primary endpoint at 28 days, PF-03187207 showed a 12% improvement over Xalatan(R) 0.005% which did not reach statistical significance. However, a statistically significant advantage over Xalatan(R) 0.005% was observed on a number of secondary endpoints (p<0.05).
Pfizer has taken the decision not to launch a global phase 3 development program for PF-03187207. Nevertheless, Pfizer has reaffirmed its commitment to the ongoing joint research program with NicOx, which aims to identify the most active nitric oxide-donating prostaglandin analogs for development on a global basis.
David Eveleth, Vice-President, Ophthalmology Development at Pfizer, commented: "We believe this phase 2 study for PF-03187207 has provided interesting data. While the study did not meet its primary clinical endpoint and our criteria for launching a global phase 3 program for this compound, we remain committed to our joint research program with NicOx, where the follow-up compounds to PF-03187207 have produced encouraging results."
The research to identify improved nitric oxide-donating prostaglandin analogs is one of the programs covered by the companies' March 2006 agreement. Several follow-up compounds from this agreement have generated promising results in a validated in vivo model of abnormally high IOP, compared to a commonly used reference drug. Pfizer's option to obtain an exclusive worldwide license to these compounds currently runs until May 2009 and their successful development and launch would result in milestone payments of euro 102 million and industry standard royalties on sales.
Pfizer is currently conducting a phase 2 study for PF-03187207 in Japan and has indicated that it would consider continuing the development of PF-03187207 for potential registration in Asia, including Japan, depending on the results of this study which are expected in Q3 2008. NicOx and Pfizer are currently in discussions regarding the rest-of-world rights to PF-03187207. Asia currently accounts for 20% of Pfizer's Xalatan(R) sales (source: IMS) (see NOTE).
Michele Garufi, Chairman and Chief Executive Officer of NicOx, commented: "We believe these results for PF-03187207 suggest nitric oxide donation can bring therapeutic benefit through improved intraocular pressure lowering. Although Pfizer has decided that PF-03187207 does not meet its specific requirements for the U.S. and European markets, we believe this phase 2 study demonstrates a clear commercial potential for PF-03187207 and we are exploring possible strategies with Pfizer to unlock this value. Moreover, the promising results from our joint research program make us confident that a follow-up candidate will be selected by Pfizer with the potential for further improvement over existing treatments."
Results of the U.S. phase 2 study
The phase 2 dose-finding study for PF-03187207 was initiated in the United States in March 2007 and was designed to compare the safety and efficacy of several doses of PF-03187207 to the marketed dose of Xalatan(R) 0.005%. The randomized, double-masked study enrolled 215 patients with primary open-angle glaucoma or ocular hypertension, in one or both eyes. Patients were randomized to receive 28 days of treatment with either morning or evening doses of Xalatan(R) 0.005%, or various doses of PF-03187207 (five different doses of PF-03187207 were tested, some of which were tested with both morning or evening dosing arms). Patients' IOP was measured at 8am, 10am, 1pm and 4pm, at baseline and on days 7, 14, 21 and 28.
The primary objective of the study was to determine if any PF-03187207 dose was superior to Xalatan(R) 0.005% for the reduction of elevated diurnal IOP (mean over the day, based on the values obtained at 8am, 10am, 1pm and 4pm) and the primary endpoint compared the two treatments in terms of the change in mean IOP from baseline at day 28. On this primary endpoint, evening administration of the highest dose of PF-03187207 showed a 12% (approximately 1 mmHg) greater reduction in diurnal IOP than evening administration of Xalatan(R) 0.005%, although this difference did not reach statistical significance.
On a secondary endpoint of the study (IOP lowering from baseline at 4pm, as an average across all study visits), evening administration of PF-03187207 was statistically significantly better than evening dosing of Xalatan(R) 0.005% by 22%, which was approximately 1.4 mmHg in absolute terms (p<0.05). This difference occurred approximately 20 hours after study drug administration, suggesting a potential clinical advantage for PF-03187207.
Maarten Beekman, Vice President of Clinical Development at NicOx, commented: "The advantage of the highest dose of PF-03187207 over Xalatan(R) was consistent over all time points and all study visits, as well as with morning and evening dosing comparisons, giving us strong confidence in these results. Furthermore, the significant difference observed at the 4pm time point is particularly interesting, as it suggests nitric oxide donation from PF-03187207 delivers a more sustained IOP lowering effect compared to Xalatan(R). The additional 1 mmHg reduction in IOP observed on the primary endpoint is comparable with that obtained by combining existing drugs with different mechanisms of action and a pivotal phase 3 study could be realistically powered to demonstrate a benefit of this magnitude."
Additional secondary endpoints were the reductions in diurnal IOP from baseline on days 7, 14 and 21, as well as the reductions from baseline at 8am, 10am, 1pm and 4pm, as an average across all study visits. Morning administration of the highest PF-03187207 dose demonstrated a statistically significant advantage compared to morning dosing of Xalatan(R) 0.005% on a number of these secondary endpoints, with the difference in IOP lowering ranging from 25% to 35%, which was approximately 1 mmHg to 2 mmHg in absolute terms (p<0.05).
There were no serious adverse events in any of the PF-03187207 and Xalatan(R) arms and most of the treatment emergent adverse events were mild or moderate. No severe conjunctival hyperemia (redness) was observed in the study, although mean hyperemia scores were higher in the PF-03187207 treated groups.
NOTE: Glaucoma is the leading cause of blindness in the United States and Japan. Pfizer's latanoprost (Xalatan(R) and Xalacom(R)) is the world's leading treatment for the disease, with approximately $1.6 billion of franchise sales globally in 2007 (IMS reports sales of Xalatan(R) in Japan of approximately $250 million in 2007).
Glaucoma is frequently associated with an abnormal build-up of fluid within the eye, which results in raised intraocular pressure (IOP) that can lead to optic nerve damage and vision loss if left untreated. Several large government trials (such as the Ocular Hypertension Treatment Study, the Collaborative Initial Glaucoma Treatment Study and the Advanced Glaucoma Intervention Study) have demonstrated that reducing IOP can prevent the progression of glaucoma in both early and late stages of the disease. A significant proportion of patients with elevated IOP require more than one medication to maintain their IOP within target levels, highlighting the need for more effective treatments. Fixed-dose combinations exist of drugs with different mechanisms of action, including Pfizer's Xalacom(R) (timolol and latanoprost).
NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) a product-driven biopharmaceutical company dedicated to the development and future commercialization of investigational drugs for unmet medical needs. NicOx is applying its proprietary nitric oxide-donating technology to develop an internal portfolio of New Chemical Entities (NCEs) in the therapeutic areas of inflammatory and cardio-metabolic disease.
Resources are focused on the development of naproxcinod, a proprietary NCE and the first compound in the Cyclooxygenase-Inhibiting Nitric Oxide-Donating (CINOD) class of anti-inflammatory agents, which is in phase 3 clinical studies for the treatment of the signs and symptoms of osteoarthritis, with final phase 3 results anticipated in Q4 2008.
Beyond naproxcinod, NicOx has a pipeline containing multiple nitric oxide-donating NCEs, which are in development internally and with partners, including Pfizer Inc and Merck & Co., Inc., for the treatment of prevalent and underserved diseases, such as atherosclerosis, hypertension, glaucoma and Chronic Obstructive Pulmonary Disease (COPD).
NicOx S.A. is headquartered in France and is listed on the Euronext Paris Stock Exchange (Compartment B: Mid Caps).
This press release contains certain forward-looking statements. Although the Company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated in the forward-looking statements.
For a discussion of risks and uncertainties which could cause actual results, financial condition, performance or achievements of NicOx S.A. to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference 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).
|SOURCE NicOx S.A.|
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