Galcanezumab in migraine prevention: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Galcanezumab, along with three other monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, represents the latest disease-specific and mechanism-based treatment for the prophylaxis of migraine. Galcanezumab shares data also for the prophylaxis of cluster headache. Objective: To provide a pooled safety and efficacy analysis of all phase III randomized controlled trials of galcanezumab in the preventive therapy of migraine. Methods: A computer-based literature search was conducted on MEDLINE and the US National Institutes of Health Clinical Trials Registry for phase III randomized controlled trials of galcanezumab in migraine prevention. The primary outcome was the mean change in monthly migraine days (MMDs). The proportions of patients who reported at least one adverse event (AE), at least one serious adverse event (SAE) or withdrew from the study were used as safety outcomes. Results: Two trials were included in the efficacy meta-analysis and three in the safety meta-analysis. Migraine preventive treatment with subcutaneous galcanezumab, at both 120 mg and 240 mg dosages, was associated with a significantly greater reduction in the mean number of MMDs versus placebo (120 mg, MD = –1.98, 95% CI = –2.33 to –1.63; p < 0.0001) or (240 mg, MD = –1.86, 95% CI = –2.20 to –1.53; p < 0.0001). Galcanezumab was found to be more efficacious in all key secondary outcomes as well. Regarding safety, most of the adverse events were mild to moderate, while drop-out rates and serious adverse events were low. Conclusions: Galcanezumab is an efficacious and well-tolerated preventive treatment for migraine. Larger clinical trials with longer follow-up periods need to be conducted in order to provide more safety data of the above-mentioned drug.

Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies

“…Prolonged absorption of mAbs from the injection site after s.c. administration is the cause of the flip-flop effect, and the peak concentration usually takes about 5-8 days of drug administration [90,97,98,101,108,111].…”

“…The volume of distribution for antibodies usually does not exceed the volume of the central compartment (3-7 L) [90,97,98,101,108,111].…”

“…Generally, mAbs administered with concomitant medications are not expected to result in clinically relevant pharmacokinetic interactions and are unlikely to affect drug-metabolizing enzymes or transporters because they are metabolized by general proteolytic degradation pathways [90,97,98,101,108,111].…”

“…The time to reach maximum serum concentration of galcanezumab is 5 days (from 7 to 14 days), the apparent volume of distribution is 7.3 L, and the half-life is 27 days [98,100,101]. Galcanezumab exposure increases proportionally with dose.…”

“…The population pharmacokinetic analysis, which included galcanezumab doses from 5 mg to 300 mg, absorption rate, apparent clearance, and apparent volume of distribution, was independent of the dose. No pharmacokinetic drug interactions are expected [98,[100][101][102][103][104]106,107].…”