Merck Updates Status of Clinical Development Programs for Investigational CGRP Receptor Antagonist Treatments for Acute Migraine; MK-3207 Clinical Development Discontinued
Company Presenting New Safety and Efficacy Data for Telcagepant at the 14th International Headache Congress
PHILADELPHIA, Sept. 10, 2009 - Merck & Co., Inc. today updated the status of the clinical development programs for telcagepant (MK-0974) and MK-3207, the Company's investigational oral calcitonin gene-related peptide (CGRP) receptor antagonists for the intermittent treatment of acute migraine. The Company provided this update in conjunction with poster presentations of new data from two Phase III clinical studies of telcagepant at the 14th International Headache Congress.
Merck is currently reviewing available clinical data for telcagepant, which is currently in Phase III of clinical development, in preparation for discussions that the Company plans to have with regulatory agencies later this year.
Separately, Merck is discontinuing the clinical development program for MK-3207, the company's other investigational CGRP receptor antagonist, and will not start confirmatory Phase IIb/III studies. While efficacy was demonstrated in a Phase II study with MK-3207, some subjects in extended Phase I clinical pharmacology studies were found to have experienced delayed, asymptomatic liver test abnormalities, generally following discontinuation of drug administration. This information led to the decision to discontinue development of MK-3207.
"Merck believes that the blocking of CGRP receptors remains an exciting pathway to address the underlying pathophysiology of migraine," said David Michelson, M.D., vice president of clinical neurosciences, Merck Research Laboratories. "We are continuing our efforts to offer patients a new treatment approach."
New long-term data for telcagepant presented at International Headache Congress
In a long-term, randomized, double-blind clinical trial, the safety and tolerability of telcagepant for the acute treatment of migraine with and without aura was assessed in patients who took either 280 mg telcagepant tablets, bioequivalent 300 mg oral soft elastic telcagepant capsule, or rizatriptan 10 mg. The primary endpoint of the study was the proportion of patients with at least one pre-specified adverse event (chest pain, chest tightness, asthenia, paraesthesia, dysaesthesia or hyperaesthesia). Patients intermittently treated up to eight acute migraine attacks per month for a period of up to 18 months. An average of 31 and 35 attacks were treated with telcagepant and rizatriptan, respectively.
Significantly fewer patients treated with telcagepant reported at least one pre-specified adverse event compared with those treated with rizatriptan (5.0 percent vs. 11.2 percent; p<0.001). The most common clinical adverse events (reported with a frequency of greater than 3 percent in either treatment group) included dry mouth, somnolence, nausea, dizziness, fatigue, nasopharyngitis, vomiting, upper abdominal pain, diarrhea, upper respiratory tract infection, asthenia and paraesthesia. Of these events, nausea (9.0 percent vs. 6.4 percent), nasopharyngitis (3.4 percent vs. 3.2 percent), vomiting (3.3 percent vs. 3.2 percent) and upper abdominal pain (3.1 percent vs. 2.2 percent) were slightly higher in the telcagepant group compared with the rizatriptan group, respectively. The other events (dry mouth, somnolence, dizziness, fatigue, diarrhea, upper respiratory tract infection, asthenia and paraesthesia) were slightly higher in the rizatriptan group compared to the telcagepant group.
In the study, three patients treated with telcagepant experienced greater than three-fold elevations in liver enzymes (without accompanying elevations in total bilirubin). All events were clinically asymptomatic, transient and deemed by the investigator to be not drug-related (one patient had a co-occurring musculoskeletal injury, one event occurred two months after the last dosing, and one event occurred in a patient who continued to treat with telcagepant without further enzyme elevations).
Study of telcagepant in acute treatment of multiple migraine attacks
The second Phase III study of telcagepant presented at the International Headache Congress showed that telcagepant was superior to placebo for acute treatment of multiple migraine attacks.
This randomized, double-blind, placebo-controlled trial assessed the consistency of response across multiple migraine attacks. A total of 1,677 adult patients who experienced at least one moderate or severe migraine attack, as defined by the International Headache Society criteria, treated up to four acute migraine attacks with either telcagepant tablets at doses of either 140 mg or 280 mg or placebo. Overall treatment effect was assessed by analyzing pain freedom, pain relief (a reduction to mild or none) and absence of migraine-associated symptoms (nausea and sensitivity to light and sound) two hours after treatment and sustained pain freedom from two to 24 hours after treatment. Both 140 mg and 280 mg doses of telcagepant were significantly more effective than placebo at all four endpoints.
Consistency of treatment effect was defined as at least three successful treatments out of four migraine attacks. When compared to placebo, a significantly greater percentage (p<0.001) of patients treated with either dose of telcagepant (140 mg or 280 mg) experienced consistency in pain freedom at two hours (9.3 percent - 140 mg, 14.1 percent - 280 mg, 2.7 percent - placebo) and consistency in pain relief at two hours (41.8 percent - 140 mg, 46.8 percent - 280 mg, 22.3 percent - placebo).
In this study, the most common adverse event with an incidence greater than two percent and at least twice that of the placebo group within 14 days of telcagepant treatment was somnolence (6.1 percent - 140 mg, 5.9 percent - 280 mg, 2.3 percent - placebo).
Telcagepant is a novel oral CGRP receptor antagonist in development for the intermittent treatment of acute migraine, which does not constrict blood vessels and works via a mechanism that does not affect serotonin. The compound is an antagonist of the receptor for CGRP, a potent neuropeptide thought to play a prominent 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, helping to transmit pain impulses. Telcagepant blocks CGRP from binding to its receptors within the nervous system and is believed thereby to inhibit the transmission of the pain signals that lead to migraine headaches.
Merck announced in April 2009 that the Company would not file a New Drug Application for telcagepant with the U.S. Food and Drug Administration in 2009 based on findings from a Phase IIa exploratory study in which a small number of patients taking telcagepant twice daily for three months for the prevention of migraine were found to have marked elevations in liver transaminases. The daily dosing regimen in the prevention study was different than the dosing regimen used in Phase III studies in which telcagepant was intermittently administered in one or two doses to treat individual migraine attacks as they occurred.
Migraines affect 1 in 10 Americans
Migraine is a disabling disorder of the brain that affects approximately 28 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.
MAXALT® (rizatriptan benzoate) is a selective 5HT1B/1D receptor agonist indicated for the acute treatment of migraine attacks with or without aura in adults. MAXALT is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and effectiveness of MAXALT have not been established for cluster headache, which is present in an older, predominantly male population. MAXALT should not be given to patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal's variant angina, or other significant underlying cardiovascular disease. Because MAXALT may increase blood pressure, it should not be given to patients with uncontrolled hypertension.
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 www.merck.com.
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, 2008, 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.