Authors: Dodick DW et al., Lancet Neurol 2014 Sep 13:885
A phase II study of a monoclonal antibody shows great promise for the first specific migraine-prevention therapy.
Calcitonin gene-related peptide (CGRP) has been a long-standing therapeutic target of interest in migraine. Small-molecule CGRP receptor antagonists demonstrated effectiveness for the treatment of acute migraine attacks, but hepatotoxicity limited their development. In this phase II, randomized, placebo-controlled, manufacturer-funded study, researchers randomized 218 adult migraineurs: 108 to LY2951742 — a fully humanized monoclonal antibody to CGRP — and 110 to placebo. At baseline, participants had approximately 7 migraine days per 28-day period. The intervention consisted of a subcutaneous injection of either 150 mg of LY2951742 or masked placebo (saline) every 2 weeks for 12 weeks, followed by an additional 12-week monitoring period for tolerability.
In the third month of treatment, the number of migraine days was significantly lower in the CGRP monoclonal antibody group (mean decline, –4.2; standard deviation, 3.1) than in the placebo group (–3.0; 3.0 mean difference, –1.2). Headache days, migraine attacks, and proportion of greater than 50% responders were also better in the CGRP monoclonal antibody group. Adverse events were similar between the two groups, with upper respiratory tract infection being most common. No treatment-related adverse events occurred.
Migraine affects an estimated 36 million Americans, yet a migraine-specific preventive medication has never before been developed. CGRP monoclonal antibodies represent the possibility of an exciting new era wherein clinicians could actually treat migraine patients with migraine-specific therapy. Although a larger, phase III study is needed, this study is reason for optimism. Further bolstering expectations that this class of medications will be a success, in a separate phase II, randomized, double-blind, placebo-controlled, manufacturer-sponsored study, the anti-CGRP antibody ALD403, delivered as a single intravenous dose, was superior to placebo in decreasing migraine frequency by the second month, without safety concerns (Headache 2014; 54 Suppl 1:1420).