Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced today that new Phase III data showed that patients with open-angle glaucoma or ocular hypertension, who were dosed once-daily with tafluprost, Merck's investigational, preservative-free prostaglandin analogue ophthalmic solution, experienced a reduction in intraocular pressure (IOP) comparable to patients taking twice-daily preservative-free timolol maleate, a beta-adrenergic antagonist. These findings were presented for the first time at the Association for Research in Vision and Ophthalmology (ARVO) 2011 Annual Meeting, held in Fort Lauderdale, FL.
"These results provide important insight into the efficacy and tolerability profile of this investigational medicine," said Tony Ho, section head of neurology and ophthalmology, Merck. "Merck recognizes the importance in developing new ophthalmic therapies. Tafluprost, if approved, will provide an additional treatment option for patients with open-angle glaucoma or ocular hypertension."
The New Drug Application (NDA) for tafluprost is under review by the U.S. Food & Drug Administration (FDA) for the proposed use in the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension. On April 15, 2009, Merck and Santen Pharmaceutical Co., Ltd. entered into a worldwide licensing agreement for tafluprost. Merck has exclusive commercial rights to tafluprost in Western Europe (excluding Germany), North America, South America, Africa, the Middle East, India and Australia. Santen retains commercial rights to tafluprost in Germany, most countries in Eastern Europe, northern Europe and in countries in the Asia Pacific region, including Japan. Merck provides promotion support to Santen in Germany. Santen will have the option to co-promote tafluprost in the U.S., if approved.
Phase III study design
The twelve-week multi-center, double-masked, randomized, active-controlled non-inferiority Phase III study of 643 patients with open-angle glaucoma or ocular hypertension was designed to evaluate the safety and efficacy of preservative-free (PF) tafluprost once-dailys primary endpoint was mean IOP change from baseline at nine time points: three times during the day (08:00 hours, 10:00 hours and 16:00 hours) at weeks two, six and 12. A secondary endpoint of the study was the proportion of patients with ≥25 percent reduction in diurnal IOP from baseline to week 12.
Efficacy results
At the beginning of the study, baseline IOPs ranged from 23.8 to 26.1 mmHg in patients treated with PF tafluprost and 23.5 to 26.0 mmHg in those treated with PF timolol. At the 12-week end of the study visit, IOPs ranged from 17.4 to 18.6 mmHg in patients treated with PF tafluprost and 17.9 to 18.5 mmHg in those treated with PF timolol. The IOP-lowering effect of treatment in patients receiving PF tafluprost and PF timolol was achieved by week two and sustained through the end of the study (week 12).
The primary endpoint of the study was measured using the Analysis of Covariance (ANCOVA) statistical method, which tests for significant differences between means taking into consideration baseline IOP and ocular diagnosis. For the primary endpoint, at all nine time points, the difference between treatments in lowering IOP was less than the prespecified 1.5 mmHg non-inferiority margin, demonstrating a comparable IOP-lowering effect in patients treated with PF tafluprost and PF timolol. In four of nine time points the difference between treatments in lowering IOP favored PF tafluprost, based on an upper 95 percent confidence interval limit of less than zero.
In addition, for a secondary endpoint the proportion of patients treated with PF tafluprost and PF timolol with ≥25 percent reduction in diurnal IOP from baseline was 56.7 percent vs. 50.5 percent at week two, 58.7 percent vs. 52.6 percent at week six, and 59.7 percent vs. 55.4 percent at week 12, respectively.
Safety results
The adverse event (AE) profiles of PF tafluprost and PF timolol were assessed over the 12-week study period. Drug-related AEs, as determined by the investigators, were experienced by 12.2 percent of patients treated with PF tafluprost and 11.1 percent of patients treated with PF timolol. Ocular AEs of special interest assessed for PF tafluprost and PF timolol, respectively, were conjunctival hyperemia (4.4 percent vs. 1.2 percent); ocular pain, stinging, and/or irritation (4.4 percent vs. 4.6 percent); and ocular pruritus (2.5 percent vs. 1.5 percent). The incidence of conjunctival hyperemia, a known prostaglandin-associated adverse event, was higher>
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