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Galcanezumab bested placebo in preventing episodic migraine with or without aura, researchers for the phase III randomized clinical trial reported.

The calcitonin gene-related peptide (CGRP) inhibitor cut monthly migraine headache days significantly relative to placebo with mild to moderate adverse effects that didn't differ substantially between groups, according to David Dodick, MD, of the Mayo Clinic in Phoenix, and colleagues.

Per-month reductions of 4.7 days for 120 mg of galcanezumab and 4.6 days for 240 mg relative to baseline were seen, versus 2.8 days for placebo (P<0.001 for both drug doses relative to placebo).

"The reduction among galcanezumab-treated patients during 6 months of treatment translates to the equivalent of approximately 8 weeks of additional migraine-free days over the course of a year," they wrote in , where they presented full data from EVOLVE-1 (top-line results were released last year). "Galcanezumab demonstrated a rapid onset of effect with a significant effect beginning at month 1 that continued through month 6."

Galcanezumab, a once-monthly, self-administered subcutaneous injection, is a humanized monoclonal antibody that targets CGRP, which is believed to play a role in migraine. The FDA recently approved the first CGRP inhibitor for migraine prevention, erenumab (Aimovig). Two other monoclonal antibodies that target CGRP -- eptinezumab and fremanezumab -- currently are in development besides galcanezumab.

CGRP inhibitors "prevent migraine expressly and specifically," explained Thomas Berk, MD, of New York University Langone Health, who was not involved in the study.

"The side effect profile of the medication [galcanezumab] is nearly equal to placebo, whereas most migraine preventive medications can be difficult to tolerate due to issues with mood, cognitive change, or light-headedness and hypotension," he told 番茄社区.

EVOLVE-1 was a double-blind, randomized, placebo-controlled trial in 90 clinics in North America that compared galcanezumab 120 mg (n=213) and 240 mg (n=212) to placebo (n=433). Patients received injections once monthly for 6 months; no other preventive medications were allowed during the study.

Qualified participants were 18 to 65 years old with at least a 1-year history of migraine, from four to 14 migraine headache days per month, and an average of at least two migraine attacks a month in the past 3 months. A total of 858 patients were included in the intent-to-treat population; their average age was 40.7 years and 83.7% were women. At baseline, they experienced about nine migraine days a month.

More patients treated with galcanezumab (20.5% for 120 mg and 19.2% for 240 mg) maintained at least a 50% reduction in monthly migraine days throughout the 6-month treatment period, versus 8.9 of the placebo group.

Onset of effect -- the earliest point in which patients reached and maintained a statistically significant improvement in migraine days from baseline -- occurred in month 1 for both galcanezumab treatment groups.

Most patients (81.9%) completed treatment; less than 5% discontinued because of adverse effects across all treatment groups. Injection site pain was the most frequently reported treatment-emergent adverse effect among all groups.

"The major limitation of the study is the fact that we simply aren't sure of the long-term effect of CGRP blockade," Berk observed. "Although the short-term side effect profile is impressive, it may be detrimental long term."

Indeed, physicians have that CGRP blockade, with its vasoconstricting effect, over time could raise the risk of myocardial infarction or ischemic stroke.

"Access to the drug may be limited, as well, due to cost and insurance coverage," Berk also pointed out, adding that it's too early to say whether one CGRP inhibitor will be better than others.

Dodick and colleagues noted their results may not apply to people outside of North America. The trial excluded pregnant women, so safety in pregnancy is unknown. And although patients with comorbid cardiovascular conditions and risks have been included in galcanezumab studies, "caution should be used when treating patients with acute cardiovascular events and/or serious cardiovascular risk because these patients have not been studied in galcanezumab clinical trials."

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