Galcanezumab shows sustained efficacy, CV safety in migraine

Not only does the CGRP* inhibitor galcanezumab show sustained efficacy in migraine patients, long-term treatment does not come with excess cardiovascular (CV) risk, according to studies presented at the AAN 2021 Annual Meeting.

In a post hoc analysis of four phase III studies on adults with chronic migraine or high frequency episodic migraine (HFEM), the researchers found no wearing off of galcanezumab efficacy compared with that of placebo at the end of the monthly treatment cycle. [AAN 2021, abstract P10.020]

“Anecdotal clinical reports suggest that some patients with HFEM or chronic migraine may experience an increase in migraine headache frequency (wearing-off) towards the end of their CGRP monoclonal antibody treatment cycle,” the researchers noted.

Based on findings of the post hoc analysis, the rates of wearing off were comparable between the galcanezumab and the placebo groups, regardless of whether patients had HFEM or chronic migraine.

Among HFEM patients, the rates of wearing off were 5.8 and 5.1 percent vs 7.0 percent for galcanezumab 120 mg and 240 mg vs placebo, respectively, in the EVOLVE-1/-2 studies. Similarly, the corresponding rates were 5.0 percent vs 4.3 percent for galcanezumab 120 mg vs placebo, respectively, in the CONQUER study.    

While the rates of wearing off were slightly higher among patients with chronic migraine, they were, again, comparable between the galcanezumab and the placebo groups (5.8 and 5.4 percent vs 3.2 percent, respectively, in REGAIN; and 9.0 percent vs 3.2 percent in CONQUER).  

Patients were randomized to monthly subcutaneous galcaneumab 120 mg, 240 mg, or placebo for 6 months in EVOLVE-1/2 (n=1176) or 3 months in REGAIN (n=1113) and CONQUER (n=391). Wearing off was defined as increase in headache frequency by of at least two headache days/week from weeks 2 to 4, during ≥2 months of months 4 to 6 in EVOLVE-1/2 and in both months 2 and 3 in REGAIN and CONQUER.

Safe for the heart

In a separate pooled analysis of five phase III placebo-controlled trials (573.41 patient-years of exposure) and nine controlled phase II and non-controlled phase III studies (1799.4 patient-years of exposure) on adults with migraine or cluster headache, researchers looked at whether long-term exposure (at least 6 months) affects the risk of CV-related adverse events (AEs). [AAN 2021, abstract P10.117]

There was no evidence of excess CV risk with long-term galcanezumab exposure — with similar proportion of patients experiencing ≥1 CV treatment-emergent AE (TEAE) in the galcanezumab vs the placebo groups (3.1 percent vs 3.3 percent) and <1 percent with a serious CV AE in both groups.

Use of CV-related medications was also similar between the two groups in the placebo-controlled studies.  

In addition, galcanezumab did not lead to excess haemodynamic changes in terms of blood pressure, pulse, and QTcF compared with placebo.

“The incidence of CV [AEs], use of CV-related concomitant medications, or haemodynamic changes did not increase with longer treatment duration, nor were there clinically meaningful differences observed between patients treated with galcanezumab or placebo,” the researchers concluded.

*CGRP: Calcitonin gene-related peptide