Effect of age on pharmacokinetics, efficacy, and safety of galcanezumab treatment in adult patients with migraine: results from six phase 2 and phase 3 randomized clinical trials

Abstract

Background: Migraine clinical profile may change with age, making it necessary to verify that migraine treatments are equally safe and effective in older patients. These analyses evaluated the effects of patient age on the pharmacokinetics (PK), efficacy, and safety of galcanezumab for prevention of migraine. Methods: Analyses included efficacy data from three double-blind phase 3 clinical trials: two 6-month studies in episodic migraine (EVOLVE-1, EVOLVE-2: N = 1773) and one 3-month study in chronic migraine (REGAIN:N = 1113). Patients were randomized 2:1:1 to placebo, galcanezumab 120 mg, or galcanezumab 240 mg. Safety and PK data included additional phase 2 and phase 3 trials for a larger sample size of patients > 60 years (range = 18-65 for all studies). Subgroup analyses assessed efficacy measures, adverse event (AE) occurrence, and cardiovascular measurement changes by patient age group. Galcanezumab PK were evaluated using a population analysis approach, where age was examined as a potential covariate on apparent clearance (CL/F) and apparent volume of distribution (V/F) of galcanezumab. Results: Numbers of baseline monthly migraine headache days were similar across age groups. There were no statistically significant treatment-by-age group interactions for any efficacy measures, except in episodic migraine studies where older patients appeared to have a larger reduction than younger patients in the number of monthly migraine headache days with acute medication use. Age (18-65) had a minimal effect on CL/F, and no effect on V/ F. Galcanezumab-treated patients ≥60 years experienced no clinically meaningful increases in blood pressure and no increased frequency in treatment-emergent AEs, discontinuations due to AEs, serious adverse events (SAEs) overall, or cardiovascular SAEs, compared to age-matched placebo-treated patients.

A long-term open-label safety study of galcanezumab in Japanese patients with migraine

“…Two global randomized controlled trials (RCTs) in patients with EM [14,15] and one in patients with CM [16], predominantly in Caucasian patients, have demonstrated that once-monthly subcutaneous (SC) injections of 120-mg or 240mg galcanezumab were safe, well tolerated, and effective in reducing the mean number of monthly migraine headache days compared with placebo. Furthermore, galcanezumab was also shown to be safe in a 12-month open-label study in the global population [17] and is safe and effective for patients over a wide range of ages [18]. More recently, a 6-month placebo-controlled RCT (I5Q-JE-CGAN) conducted in Japanese patients with EM reported similar results [19].…”

Indirect Comparison of Topiramate and Monoclonal Antibodies Against CGRP or Its Receptor for the Prophylaxis of Episodic Migraine: A Systematic Review with Meta-Analysis

“…Clinical use led to the impression that CGRP antibody medications have a better tolerability profile than the standard of care (SoC) oral migraine prophylactic agents. However, adverse event (AE) rates in mAbs trials range between 60 and 70% [ 4 – 6 ].…”

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

“…Anti-CGRP monoclonal antibodies are less hepatotoxic than gepants, their metabolism is based on reticuloendothelial uptake. Since monoclonal antibodies are not known to be eliminated via renal pathways or metabolized in the liver, renal and hepatic impairment are not expected to impact their pharmacokinetics [111][112][113][114][115][116][117][118].…”

“…Galcanezumab (EMGALITY, solution for subcutaneous injection, 120 mg in pre-filled pen) is a recombinant humanised monoclonal antibody produced in CHO cells. The FDA and EMA approved the drug; the recommended dosage is one subcutaneous injection at a dose of 120 mg once a month with the first loading dose of 240 mg [113][114][115]. Galcanezumab has been shown to be effective also in prevention of cluster headache attacks [99,105].…”