The CGRP receptor antagonist shows similar benefits for migraine as zolmitriptan, with fewer adverse events. Researchers believe the drug may be a better treatment option than triptans, narcotics, opiates, and barbiturates.
SEATTLE—Telcagepant, a novel, oral calcitonin gene-related peptide (CGRP) receptor antagonist, is comparable in efficacy and safety to zolmitriptan for the acute treatment of migraine with and without aura, researchers reported at the 61st Annual Meeting of the American Academy of Neurology. Tony W. Ho, MD, and colleagues from Merck Research Laboratories in North Wales, Pennsylvania, suggested that CGRP is a preferable alternative to triptans, narcotics, opiates, and barbiturates, which are sometimes associated with adverse side effects, and in the case of triptans, poor long-term patient compliance.
“There’s a great need for a new mechanism for acute migraine therapy,” Dr. Ho stated. “CGRP receptor antagonists block the action of CGRP at multiple sites, both peripheral and in the CNS, and inhibit migraine pain transmission.” Due to CGRP’s presence throughout the CNS, investigators have hypothesized that it has a sensory role in migraine pathophysiology; migraine pain occurs when CGRP levels elevate, causing photophobia and phonophobia.
Achieving Pain Freedom
Two phase III, randomized, double-blind, placebo-controlled trials were reported. In the first study, 333 patients received 150 mg telcagepant, 354 received 300 mg telcagepant, 345 received 5 mg zolmitriptan, and 348 were given placebo. Co-primary end points were pain relief (reduction to mild or none), pain freedom, and reduction of photophobia, phonophobia, and nausea, at two hours postdose. Sustained pain freedom from two to 24 hours postdose was the secondary endpoint.
Efficacy was similar for 300 mg telcagepant and 5 mg zolmitriptan, although 150 mg telcagepant was slightly less effective than zolmitriptan. Telcagepant was more effective in achieving two-hour pain freedom at both doses than placebo, as was zolmitriptan. Telcagepant was also associated with sustained pain freedom, relative to placebo. Zolmitriptan showed similar efficacy to telcagepant at 300 mg. “All doses of telcagepant and zolmitriptan were generally well tolerated,” Dr. Ho and coinvestigators stated. Adverse events rates were 31.4% and 37.2%, respectively, for telcagepant 150 mg and 300 mg, and 50.7% and 32.1%, for zolmitriptan and placebo, respectively.
The second study compared 177 participants taking 50 mg telcagepant, 381 taking 150 mg telcagepant, 371 taking 300 mg telcagepant, and 361 taking placebo. Telcagepant was more effective than placebo at doses of 300 mg and 150 mg. Adverse events rates were 32.2%, 32.0%, and 36.2% for 50 mg, 150 mg, and 300 mg of telcagepant, respectively. The adverse event rate for placebo was comparable to 50 mg of telcagepant.
In a post-hoc analysis, Dr. Ho and colleagues found that participants who described their general response to triptans as good, intermediate, or poor had the same response to zolmitriptan in the trials. However, the efficacy of telcagepant was consistent and did not correlate with participants’ general triptan response.
The efficacy of telcagepant 300 mg and 150 mg for acute migraine was demonstrated in both trials, according to Dr. Ho. “Telcagepant was generally well-tolerated, with overall adverse event rates that were comparable to placebo,” he said.
—Laura Sassano