Efficacy and Safety of Galcanezumab for the Preventive Treatment of Migraine: A Narrative Review

DOI: https://doi.org/10.1007/s12325-020-01319-9

Abstract-Summary People who experience migraine can have substantial disability, impaired function- ing and a decreased quality of life (QoL).

692

4 Treatment

Expert recommendations suggest that people with frequent migraine attacks or

severe impairment related to attacks may benefit from preventive treatment. There is still a substantial unmet need for preventive migraine treatment. The aim of this review is to present a comprehensive overview of the existing short- and long-term efficacy and safety data for galcanezumab in patients with migraine.

Data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2 and REGAIN studies show that galcanezumab treatment for 3 or 6 months results in overall reduction in mean monthly migraine headache days in patients with episodic (EVOLVE-1 and EVOLVE-2) and chronic (REGAIN) migraine.

Greater proportions of patients with episodic migraine receiving galcanezumab versus placebo demonstrated a ≥ 50%, ≥ 75% and 100% response to therapy and reported a lower level of disability and an improvement in functioning and QoL. Similarly, when compared with placebo, greater proportions of patients with chronic migraine treated with galcanezumab demonstrated a ≥ 50% and ≥ 75% response and reported improved functioning.

A 12-month open-label study demonstrated the continued efficacy of galcane-

zumab for up to 12 months.

Data from pivotal studies show that galcanezumab may fulfill an unmet need in

the treatment of patients with migraine who require preventive therapy.

Introduction Individuals with infrequent migraine attacks can often manage them with acute treatments, but preventive treatment may be needed if attacks are more frequent or result in severe impairment [170].

In a more recent survey of 21,143 patients with migraine, around 25% of patients meeting criteria to be offered preventive treatment reported ever taking a preventive medication [171].

This suggests there is still a substantial unmet need for preventive migraine

treatment.

The infusion of CGRP in patients with migraine can induce migraine-like attacks, and CGRP levels have been shown to decrease after administration of acute treat- ments for migraine [172], suggesting a role for CGRP in migraine [173].

It is administered as a once-monthly subcutaneous injection and has been shown to be effective in several short- term (≤6 months) phase 2 [174–176] and phase 3 [177–179] studies in patients with episodic or chronic migraine.

A long-term 12-month open-label study in patients with episodic or chronic migraine has demonstrated the continued safety and efficacy of galcanezumab [180].

Pivotal Studies of Galcanezumab The efficacy and safety of galcanezumab in the prevention of migraine was evalu- ated in four phase 3 clinical trials: EVOLVE-1, EVOLVE-2, REGAIN and a long- term open-label safety study.

REGAIN was also a multicenter, randomized, double-blind, placebo-controlled design and used the same galcanezumab dosage regimens as EVOLVE-1 and -2, but it was a 12-month study (3-month double-blind period plus 9-month open-label

4.2 Preventive Treatment

693

period not reported herein) conducted in patients with chronic migraine (≥15 head- ache days per month of which ≥8 were MHDs) [177].

The long-term, open-label safety study investigated the safety, tolerability and efficacy of galcanezumab using the same dose regimens as the EVOLVE and REGAIN studies for up to 12  months in patients with episodic or chronic migraine [180].

Overview of Key Data from the Evolve-1, Evolve-2 and Regain Studies The EVOLVE studies demonstrated that galcanezumab treatment was superior to placebo in terms of reducing the mean number of monthly MHDs in patients with episodic migraine over a 6-month treatment period [178, 179].

In the EVOLVE studies, MIDAS was measured at baseline, 3 and 6 months, and

MSQ RF-R was measured monthly.

Regarding reductions in mean monthly MHDs with acute medication use, only the reduction in the galcanezumab 240  mg group was significantly greater than placebo (p  <  0.001); the reduction with galcanezumab 120  mg was nominally greater than placebo (nominal p value <0.001).

In REGAIN, the MIDAS score was measured at baseline and 3 months, and the

MSQ RF-R was measured monthly.

A greater number of patients in the galcanezumab groups than the placebo

groups reported TEAEs [177–179].

Overview of Open-Label Safety Study Outcomes We report the results from a 12-month open-label study in patients with chronic and episodic migraine [180].

Patients enrolled in this study were a separate group to those participating in the EVOLVE and REGAIN studies and had no prior exposure to galcanezumab or any other CGRP antibody.

More than 65% of patients receiving galcanezumab had a ≥50% response in this study, and ≥75% and 100% responses were seen in at least 44% and 21% of patients, respectively [180].

Patient-reported outcomes had also improved from baseline to 12 months in both galcanezumab 120 mg and 240 mg groups in this study, with respect to both the MIDAS total score (least squares mean reductions: −33.6 and −32.7) and the MSQ RF-R (least squares mean increases: 31.6 and 33.4) [180].

Discussion Data from the pivotal studies of galcanezumab show that it is effective in patients with episodic or chronic migraine, with improvements in monthly MHDs seen as early as 1 month.

Considering the impact that side effects can have on the long-term use of pre- ventive medications, it is notable that discontinuations due to AEs were not fre- quent in the phase 3 galcanezumab studies, and the study completion rates were high (>80%).

Since preventive treatment discontinuation is associated with loss of efficacy [181], the high rates of completion seen in these galcanezumab studies may also reflect patient satisfaction levels with persistence of effect through 12 months.

694

4 Treatment

An additional factor for the sustained efficacy seen in studies of galcanezumab may be its once-monthly administration schedule which, in the long-term open- label study, included self-administration at home by patients or their caregiv- ers [180].

This shows that prior to galcanezumab treatment, patients included in these stud-

ies were severely disabled by their migraine attacks.

Conclusions Data from pivotal phase 3 studies show that galcanezumab is effective for the pre- ventive treatment of migraine and has an acceptable safety profile.

Galcanezumab provides a new treatment option with a novel mechanism of

action to patients with migraine.

Acknowledgement A machine generated summary based on the work of Martin, Vincent; Samaan, Karen Hamrick; Aurora, Sheena; Pearlman, Eric M.; Zhou, Chunmei; Li, Xiaoping; Pallay, Robert. 2020 in Advances in Therapy.

Calcitonin gene-related peptide (receptor) antibodies: an exciting avenue for migraine treatment