NicOx S.A. announced the results of a US phase II study, conducted by its partner Pfizer Inc, which compared the safety and efficacy of various doses of PF-03187207 to Xalatan (latanoprost) 0.005 per cent 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 0.005 per cent, at all study visits and at all in dividual 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 per cent improvement over Xalatan 0.005 per cent which did not reach statistical significance. However, a statistically significant advantage over Xalatan 0.005 per cent was observed on a number of secondary endpoints.
Pfizer has taken the decision not to launch a global phase III development programme 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 II 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 III programme for this compound, we remain committed to our joint research programme 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 €102 million and industry standard royalties on sales.
Pfizer is currently conducting a phase II 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 per cent of Pfizer's Xalatan. 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 US and European markets, we believe this phase II 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 programme make us confident that a follow-up candidate will be selected by Pfizer with the potential for further improvement over existing treatments".
Maarten Beekman, vice president of clinical development at NicOx, commented, "The advantage of the highest dose of PF-03187207 over Xalatan 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 4 pm time point is particularly interesting, as it suggests nitric oxide donation from PF-03187207 delivers a more sustained IOP lowering effect compared to Xalatan. 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 III study could be realistically powered to demonstrate a benefit of this magnitude".