LOS ANGELES — The experimental drug telcagepant for acute migraine therapy appears to be tolerated by patients with stable coronary artery disease and to be consistently effective in various subgroups of patients, according to several analyses of randomized, double-blind, placebo- or active-controlled studies.
Previous studies have shown that telcagepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, is effective in acute treatment of migraine (Neurology 2009;73:970-7; Lancet 2008;372:2115-23; Neurology 2008;70:1304-12).
The new analyses were led by employees of Merck, which is developing telcagepant and which funded the studies. Merck also had been developing the drug for migraine prophylaxis, but stopped those trials when some patients taking twice-daily doses for 3 months developed elevated liver enzyme levels, a company spokeswoman said in an e-mail interview after the meeting. Following discussions with the Food and Drug Administration at the end of 2009, Merck is conducting an additional safety study this year before regulators consider the drug further—a 6-month study of 4,500 females with menstrually associated migraine who will take 140 mg of telcagepant or placebo once daily for 7 consecutive days on a monthly basis.
No Cardiovascular Problems Noted
A double-blind, crossover study randomized patients with migraines and stable coronary artery disease to one of two treatment groups. Patients in the first group treated up to 12 moderate to severe migraines with telcagepant in a 280-mg tablet plus a 300-mg capsule during a 6-week period, then treated 12 more migraines in the next 6-week period with acetaminophen 1,000 mg. Patients in the second group got placebo for the first moderate to severe migraine attack, then acetaminophen for up to 11 more migraines in the first 6-week period; in the second 6 weeks, up to 12 migraines were treated with the telcagepant regimen.
Final data were available to analyze safety in 184 patients and efficacy in 105 patients.
Adverse events were reported within 48 hours of treatment by 17 of 98 patients on telcagepant (17%) and 9 of 86 patients on acetaminophen (10%), reported Dr. Tony Ho, senior director of clinical research at Merck Research Laboratories, North Wales, Penn., and his associates. Drug-related adverse events were reported by eight patients (8%) on telcagepant and four (5%) on acetaminophen. No patients stopped treatment because of adverse events.
Three serious vascular events—two reports of chest pain after telcagepant and one report of renal artery stenosis after acetaminophen—were sent for adjudication by a blinded independent expert committee. The committee declared all to be non-thromboembolic events, and each occurred longer than 48 hours after migraine treatment. No patients had transaminase elevations three times the upper limit of normal or higher.
The study did not find significant differences in efficacy, perhaps because of the small number of patients, the investigators suggested. No pain was reported in 13 (25%) of 52 patients 2 hours after taking telcagepant, compared with 10 (19%) of 53 patients on placebo.
The apparent lack of a significant risk of using telcagepant in patients with coronary artery disease is a huge plus. The drug could be an alternative for patients who can't take triptans, Dr. Leslie Kelman, medical director of the private practice Headache Center of Atlanta, said in an interview. He was not involved in the telcagepant studies.
Efficacy in Migraine Subgroups
A pooled analysis of single-attack data from three randomized, double-blind, placebo-controlled studies involving a total of 3,829 patients compared the efficacy of 140 mg or 150 mg of telcagepant, 280 mg or 300 mg of the drug, or placebo.
For migraine with aura, 21% of 230 patients on the lower doses of telcagepant and 28% of 222 patients on the higher doses were pain-free 2 hours after treatment, compared with 10% of 233 patients on placebo. For migraine without aura, 21% of 1,020 patients on lower-dose telcagepant, 24% of 1,019 patients on higher doses, and 10% of 996 patients on placebo were pain-free after 2 hours. Rates were higher for pain relief at 2 hours but similar between aura and no-aura subgroups.
For menstrually associated migraines, 52% of 216 patients on lower doses and 56% of 209 on higher doses were pain-free after 2 hours, compared with 29% of 221 patients on placebo. For non-menstrual migraines, 54% of 571 patients on lower doses, 60% of 557 on higher doses, and 33% of 557 on placebo were pain-free at 2 hours, Dr. Ho and his associates reported.
Among patients who reported that previous migraine treatment with a triptan was of “no use,” 62% of 343 patients on the lower doses of telcagepant and 56% of 339 on the higher doses were pain-free after 2 hours, compared with 39% of 346 patients on placebo.