More phase II success for CGRP migraine prevention strategy

Feb 18 2016

By Eleanor McDermid

Another antibody targeting the calcitonin gene-related peptide (CGRP) pathway has proved successful against episodic migraine in a phase II trial.

The antibody, AMG 334, is a fully human immunoglobulin G2 monoclonal antibody that directly binds to the CGRP receptor, in contrast with previously tested antibodies that bind to the ligand.

The physiological role of CGRP is to dilate arteries, increasing blood flow to vital organs. So in theory an antibody that blocks the receptor rather than the ligand "could translate to improved safety in situations of cardiovascular stress, although this is something which remains to be tested", say Marta Ramos (Hospital Occidente de Kennedy and University La Sabana, Bogotá, Colombia) and Julio Pascual (University Hospital Marqués de Valdecilla and IDIVAL, Santander, Spain) in a commentary accompanying the study.

The 466 patients were aged around 40 years, on average, and had between 4 and 15 migraine days, averaging nearly 9 days. They received AMG 334 or placebo as a monthly subcutaneous injection.

The randomised trial, which is published in The Lancet Neurology, demonstrated a dose-response for AMG 334; the 2.2- and 2.4-day reductions in monthly migraine days achieved with the lower 7 and 21 mg doses were not significant versus placebo. The 70 mg dose achieved a 3.4-day reduction in monthly migraine days over 12 weeks of use, resulting in a significant 1.1-day reduction relative to the 2.3-day reduction seen in the placebo group.

The reduction achieved was in line with that reported in phase II trials of other antibodies targeting the CGRP pathway, but Ramos and Pascual ask whether a reduction of 1.1 days for a patient with 8-9 migraine days at baseline is "clinically meaningful", and suggest that further exploration of higher doses is needed.

Thirty percent of patients in the placebo group achieved a 50% reduction in the number of migraines per month compared with 29% and 34% in the 7 and 21 mg groups, respectively, and a significantly better 46% in the 70 mg group, report researcher Robert Lenz (Amgen, Thousand Oaks, California, USA) and team.

"Interestingly, in all clinical trials with the different antibodies, at least 15% of participants noticed complete relief, which could mean that the antibodies could be very efficacious in a subset of migraine patients in whom CGRP plays a crucial part", say Ramos and Pascual.

Adverse event rates were similar between the groups and were low, with the most common events of nasopharyngitis occurring in between 5% and 9% of patients. Ten percent of patients who received AMG 334 developed antibodies against the medication.

The commentators say: "Although this proportion seems low, this is a short-term trial and it is fair to speculate that the development of these antibodies could be an obstacle in some patients needing prolonged treatment, such as those with high-frequency or chronic migraine."

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