Merck’s investigational prostaglandin analogue ophthalmic medication tafluprost meets primary endpoint in phase III study

WHITEHOUSE STATION, N.J., May 2, 2011 — 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-daily (n=320) and PF timolol twice-daily (n=323) over a 12-week treatment period. The study’s 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 (p=0.016) in the group receiving PF tafluprost compared to the PF timolol group. Serious AEs were reported in 0.6 percent of patients in the PF tafluprost group and 2.2 percent in the PF timolol group, but none of the AEs reported in either treatment group were assessed by the investigators as drug-related. In the PF tafluprost group, 1.3 percent of patients discontinued because of drug-related AEs, compared with 0.9 percent in the PF timolol group.

Poster presentation


Randomized Clinical Trial of the Efficacy and Safety of Preservative-free Tafluprost and Preservative-free Timolol in Patients with Open-angle Glaucoma (OAG) or Ocular Hypertension (OHT) (Poster # A520).

About Merck

Today’s Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com.

About Santen

Santen Pharmaceutical is a pharmaceutical company based in Osaka, Japan, which specializes in ophthalmic and anti-rheumatic fields. Santen contributes to maintaining people’s
eyesight and health. Santen applies its efforts mainly in ophthalmology, in order to contribute to the quality of life of the patient and their loved ones, and society as a whole. For details please access www.santen.com.

Forward-looking statement

This news release includes “forward-looking statements” within the meaning of the safe
harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such
statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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