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.