Merck update on the status of telcagepant clinical development programs

Sep 11 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 14^th 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).

http://www.merck.com/