NEW YORK (Reuters Health) – Injections of the calcitonin-gene-related peptide (CGRP) monoclonal antibody galcanezumab reduce monthly headache days in patients with episodic migraine, according to results from the EVOLVE-1 phase 3 study.
Galcanezumab prevents the biological activity of CGRP, which has been implicated in the pathophysiology of migraine, without blocking the CGRP receptor. Eli Lilly and Company, which funded the new work, submitted a Biologics License Application for galcanezumab to the U.S. Food and Drug Administration in December 2017.
Dr. David W. Dodick from Male Clinic in Phoenix, Arizona, and colleagues from 90 sites in North America investigated the efficacy of two doses of galcanezumab, given monthly by subcutaneous injection (120 mg and 240 mg), versus placebo in 858 patients with episodic migraine with or without aura.
At baseline, mean monthly migraine headache days (MHDs) were 9.1, mean monthly migraine attacks were 5.7, mean monthly headache hours were 60.6 and mean baseline Migraine Disability Assessment (MIDAS) scores were 33.2.
Mean monthly MHDs, the primary endpoint, decreased to a significantly greater extent with galcanezumab 120 mg (by 4.7 days) and galcanezumab 240 mg (by 4.6 days) than with placebo (by 2.8 days).
A significant benefit of galcanezumab versus placebo was seen as early as the first month, the researchers report in JAMA Neurology, online May 29.
Both doses of galcanezumab were superior to placebo in the proportion of patients who maintained at least 50% response for six consecutive months of treatment (20.5% of those treated with galcanezumab 120 mg; 19.2% of those treated with galcanezumab 240 mg; and 8.9% of those treated with placebo).
Mean monthly headache hours decreased by 29.7 hours with galcanezumab 120 mg, by 29.3 hours with galcanezumab 240 mg and by 15.7 hours with placebo (P<0.001).
Both galcanezumab doses showed improvements superior to those with placebo for Migraine-Specific Quality of Life Questionnaire (MSQ), Patient Global Impression of Severity (PGI-S) and MIDAS scores.
The percentage of patients who reported at least one treatment-emergent adverse event was non-significantly greater in the galcanezumab groups than in the placebo group.
“These data provided consistent, clinically meaningful evidence that treatment with galcanezumab reduced migraine frequency and migraine-related disability and improved patient functioning,” the researchers conclude.
Dr. Philip R. Holland from King’s College London, who recently reviewed the CGRP pathway and its role in migraine, told Reuters Health by email, “The ‘Umabs’ have arrived, and your patients are going to be contacting you looking to get them now.”
“Cost implications will make galcanezumab unlikely to be a general first-level preventative; however, in those who have failed other preventatives (and there are many), this is an important option,” said Dr. Holland, who was not involved in the new work. “The early effect (seen with other Umabs also) will also open the door for a short-term commitment (3 months) and revaluation when efficacy can be better predicted in individual patients.”
Dr. Uwe Reuter from Charite-Universitaetsmedizin Berlin, who also was not involved in the new work, recently reviewed monoclonal antibody therapies and other preventive treatments for migraine. “For now it is too early to recommend a monoclonal antibody as first-line preventive therapy,” he told Reuters Health by email, adding that monoclonal antibodies might be appropriate for “subjects who have failed other first-line preventatives or cannot tolerate these due to adverse effects.”
Eli Lilly employed several of the authors.
Dr. Dodick did not respond to a request for comments.
JAMA Neurol 2018.