Merck & Co., Inc. announced that, in a Phase III clinical trial, telcagepant (formerly MK-0974), its investigational oral calcitonin gene-related peptide (CGRP) receptor antagonist, significantly improved relief of migraine pain and migraine-associated symptoms two hours after dosing compared to placebo. In addition, the efficacy results for telcagepant 300 mg were similar to the highest recommended dose of zolmitriptan,1 an approved migraine therapy, with a lower incidence of adverse events associated with telcagepant in this study. The new data were presented here at the American Headache Society (AHS) annual meeting.

This trial is part of an ongoing Phase III program evaluating telcagepant. While Phase II and Phase III trials have used a liquid-fill capsule (including the study presented here), telcagepant has been successfully reformulated into a solid tablet that is being evaluated in ongoing trials. Merck continues to anticipate filing a New Drug Application (NDA) for telcagepant with the U.S. Food and Drug Administration in 2009.

"These findings provide further support for the development of telcagepant as a potential new acute migraine treatment based on its novel mechanism of action targeting CGRP," said Paul Winner, D.O., F.A.A.N., clinical study investigator and director of both Premiere Research Institute and Palm Beach Headache Center, West Palm Beach, Florida. "Based on this initial large study, the investigational compound telcagepant relieved migraine pain and migraine associated symptoms comparable to a triptan medication but with fewer side effects."

Nearly 1,400 patients treated for migraine attack in this trial

The reported findings are from a randomized, double-blind, placebo- and active-controlled Phase III study in patients with migraine. A total of 1,380 adult patients who experienced a single moderate or severe migraine attack, as defined by the International Headache Society criteria, were treated with either telcagepant (as a liquid-filled soft gel capsule) at doses of either 150 mg (n=333) or 300 mg (n=354) or zolmitriptan 5 mg (n=345) or placebo (348). Patients enrolled were primarily women (85 percent) with an average age of 43 years.

Overall treatment effect was assessed by analyzing five primary endpoints at two hours post-dose: pain relief (reduction to mild or none); pain freedom (reduction to no pain); absence of sensitivity to sound (phonophobia); absence of sensitivity to light (photophobia); and absence of nausea. Sustained pain freedom from two to 24 hours (defined as those with no pain at two hours who remain free of pain during the two-24 hour period with no use of optional second study dose or rescue medication); total migraine freedom (TMF) (defined as no pain and absence of nausea, photophobia and phonophobia) at two hours post-dose; and TMF from two-24 hours were secondary endpoints of the study. The study was not designed to show equivalence or non-inferiority of telcagepant versus zolmitriptan.

Telcagepant relieved migraine pain and migraine associated symptoms in study

The treatment effect of the 300 mg dose of telcagepant was significantly greater than placebo for all five primary endpoints in the study (p=<0.01 for freedom from nausea and p<0.001 for all others) and comparable to zolmitriptan, as follows:

- Two-hour pain relief: 55 percent of patients who received telcagepant reported their pain had been reduced at two hours compared to 56 percent for zolmitriptan and 28 percent for placebo;

- Two-hour pain freedom: 27 percent of patients who received telcagepant reported being pain free at two hours compared to 31 percent for zolmitriptan and 10 percent for placebo;

- Absence of phonophobia: 58 percent of patients who received telcagepant reported they were not experiencing sensitivity to noise at two hours compared to 55 percent for zolmitriptan and 37 percent for placebo;

- Absence of photophobia: 51 percent of patients who received telcagepant reported they were not experiencing sensitivity to light compared to 50 percent for zolmitriptan and 29 percent for placebo; and

- Absence of nausea: 65 percent of patients who received telcagepant reported they were not experiencing nausea compared to 71 percent for zolmitriptan and 55 percent for placebo.

Secondary endpoints also evaluated

For the endpoint sustained pain freedom from two to 24 hours post-dose, the response rate was greater in patients who received telcagepant compared to those receiving placebo and was comparable to those receiving zolmitriptan. A similar pattern was observed for the measures of TMF at two hours and TMF at two-24 hours post-dose. Responses to sustained pain freedom at two-48 hours, an exploratory endpoint, also were reported and showed that more patients who received telcagepant reported being free of migraine pain up to 48 hours compared to those receiving zolmitriptan or placebo.

Telcagepant adverse event rates

In this large trial, rates of overall adverse events observed in patients treated with telcagepant 300 mg (37 percent) were similar to placebo (32 percent) and lower than those treated with zolmitriptan (51 percent). The most common side effects occurring in patients treated with telcagepant were dry mouth (6 percent), dizziness (5 percent), somnolence (5 percent), nausea (5 percent) and fatigue (4 percent). There were no reports of serious adverse events in the telcagepant or zolmitriptan treatment arms.

Additional efficacy and safety data for telcagepant also presented

In addition to the large Phase III study, three additional posters with telcagepant will be presented during the AHS meeting, including:

- a post-hoc analysis of the reported Phase III study evaluating patient-level data using the exploratory endpoint sustained pain freedom and no adverse events (SPFNAE) [Poster #S6];

- a double-blind, randomized, placebo-controlled cross-over study evaluating the effects of telcagepant in patients with stable coronary artery disease [Poster #S1]; and

- a preclinical study evaluating the pharmacologic effects of telcagepant administered with nitroglycerin [Poster #S58].

The safety data presentations [Posters #S1 and S58] are part of a comprehensive evaluation underway to further evaluate the cardiovascular safety profile of telcagepant.

Telcagepant is a CGRP blocker, potentially a new mechanism to treat migraines

Telcagepant is a novel, oral CGRP receptor antagonist without direct vasoconstriction in development for treatment of acute migraine. It is an antagonist of the receptor for CGRP, a potent neuropeptide thought to play a central role in the underlying pathophysiology of migraine. CGRP and its receptors are found in many areas of the brain that are important for the transmission of migraine pain. During migraine attacks, CGRP binds to and activates CGRP receptors, which helps transmit pain impulses. Telcagepant blocks CGRP from binding to its receptors within the nervous system and thereby is believed to inhibit the transmission of the pain signals that lead to migraine headaches.

Migraines affect 1 in 10 Americans

Migraine is a disabling disorder of the brain that affects 35 million Americans, primarily women. Unlike a bad headache, migraines are characterized by attacks of intense, usually one-sided, throbbing head pain that can last from four to 72 hours. The pain associated with migraine is frequently accompanied by other symptoms, including nausea, vomiting and increased sensitivity to light and sound.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit http://www.merck.com.

Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007 and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.

1 ZOMIG is the registered trade name for zolmitriptan, which is marketed by AstraZeneca.

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