Philadelphia, PA—Two investigational monoclonal antibodies against the calcitonin gene-related peptide (CGRP) proved safe and effective at preventing migraine in a pair of phase 2, placebo-controlled, proof-of-concept trials, researchers reported at the 2014 American Academy of Neurology meeting.
These findings warrant “cautious optimism that a new mechanism-based, disease-specific migraine prevention is in sight,” said David W. Dodick, MD, FACP, Professor of Neurology, Mayo Clinic, Phoenix, AZ, and lead investigator of one of the trials.
CGRP is a therapeutic target because this sensory neuropeptide is released during migraine and acts as a trigger for attacks, Dr Dodick said. It is involved in neurogenic inflammation and promotes vasodilation. Levels of CGRP are normalized by triptan drugs. Several CGRP receptor antagonists have demonstrated efficacy in the acute treatment of migraine.
CGRP Receptor LY2951742
Dr Dodick presented a study involving the CGRP receptor LY2951742, which has >10,000-fold selectivity for CGRP compared with related peptides.
A total of 217 patients who had migraines on 4 to 14 days monthly received 150-mg injections of LY2951742 or placebo every 2 weeks for 12 weeks. At baseline, patients had a mean of 7 migraine days monthly.
The mean reduction in monthly migraines was 4.2 days in the LY2951742 group compared with 3 monthly migraines with placebo (P = .003). By month 3, there were 3 times more responders (defined as >50% reduction in migraine days) with LY2951742 than with placebo.
LY2951742 was safe and well tolerated, with no clinically meaningful changes on patients’ electrocardiograms, no prolongation of the QT interval, and no evidence of hepatotoxicity. The adverse events that occurred more often with LY2951742 included injection-site pain, upper respiratory tract infections, and abdominal pain.
CGRP Receptor ALD403
The second study involved the CGRP receptor ALD403 in 163 patients who had 5 to 14 migraine days monthly. They were randomized to a single hour-long infusion of 1000 mg of ALD403 or to placebo and were followed for 3 months. Migraine data were collected electronically from patient diaries.
ALD403 met the primary end point of significantly reducing the mean monthly migraine days compared with placebo (–5.6 days vs –4.6 days) during weeks 5 to 8, reported Peter J. Goadsby, MD, PhD, DSc, King’s College London, England, and Director, Headache Center, University of California, San Francisco. However, the difference was no longer significant at week 12.
Depending on the month of observation, ALD403 resulted in a 100% reduction in migraines in 27% to 41% of patients. Approximately 16% of patients in the ALD403 group were free of migraines for the full 3-month study period compared with none of the patients in the placebo group.
There were no biochemical changes in the ALD403 group and the agent appeared safe—the rates of adverse events were 56% with ALD403 and 50% with placebo.