Further monthly injectable migraine prophylactic launched

With the launch of Emgality (galcanezumab), prescribers can now choose from three injectable CGRP antagonists as prophylactic options for people who experience 4 or more migraines a month.

CGRP antagonists are a new class of migraine prophylactics. | THE PRINCESS MARGARET MIGRAINE CLINIC CHARING CROSS HOSPITAL/SPL
CGRP antagonists are a new class of migraine prophylactics. | THE PRINCESS MARGARET MIGRAINE CLINIC CHARING CROSS HOSPITAL/SPL

Galcanezumab is a humanised monoclonal antibody that binds and inhibits the activity of calcitonin gene-related peptide (CGRP). Elevated blood concentrations of CGRP have been associated with migraine attacks. Galcanezumab is the third CGRP antagonist to be launched in the UK after erenumab (Aimovig) and fremanezumab (Ajovy).

The efficacy and safety of galcanezumab were studied in 3 phase III, randomised, placebo-controlled, double-blind studies in a total of 2886 adults. The episodic migraine studies (EVOLVE-1 and EVOLVE-2) enrolled patients who met International Classification of Headache Disorders (ICHD) criteria for a diagnosis of migraine with or without aura with 4-14 migraine headache days per month. The chronic migraine study (REGAIN) enrolled patients who met ICHD criteria for chronic migraine with ≥15 headache days per month, of which at least 8 had the features of migraine.

Patients received monthly doses of placebo, galcanezumab 120mg (with an initial loading dose of 240mg) or galcanezumab 240mg and were allowed to use medication for the acute treatment of migraine.

Participants were predominantly female (>83%) with a mean age of 41 years, and an average migraine history of 20 to 21 years. Approximately one-third of patients across the studies had failed to respond to at least 1 prior migraine prophylactic.

In all 3 studies, the overall mean change from baseline in number of monthly Migraine Headache Days (MHDs) was the primary efficacy measure. The impact of migraine on functioning was assessed by the Role Function-Restrictive domain of the Migraine-Specific Quality of Life Questionnaire (MSQ) version 2.1, and by the Migraine Disability Assessment (MIDAS) Questionnaire. 

Patients with recent acute cardiovascular events (including MI, unstable angina, CABG, stroke, DVT) and those deemed to be at serious cardiovascular risk were excluded from all the trials. 

Episodic migraine

In EVOLVE-1 and EVOLVE-2 both galcanezumab 120mg and 240mg groups showed significant and clinically meaningful improvements from baseline compared to placebo in mean change in MHD (EVOLVE-1: reductions of -4.7 days and -4.6 days, respectively, vs 2.8 days for placebo; EVOLVE-2: reductions of -4.3 and -4.2 days, respectively, vs 2.3 days for placebo; p < 0.001 for all comparisons). Patients treated with galcanezumab had greater response rates and greater reductions in the number of monthly MHDs requiring acute medication compared with placebo-treated patients.

Galcanezumab-treated also patients had a greater improvement in functioning (as measured by the MSQ Role Function-Restrictive domain score) compared with placebo-treated patients, beginning at month 1. More patients treated with galcanezumab achieved clinically meaningful levels of improvement in functioning (responder rate based on MSQ Role Function Restrictive domain) compared with those treated with placebo. Galcanezumab was associated with a significant reduction in disability over placebo.

Chronic migraine

Participants in REGAIN entered a 3-month, double-blind, placebo-controlled treatment period followed by a 9-month open-label extension. Approximately 15% of patients continued concurrent prophylactic treatment with topiramate or propranolol, as allowed by the protocol.

Both galcanezumab 120mg and 240mg groups showed significant and clinically meaningful improvements from baseline compared to placebo in mean change in MHD (reductions of −4.8 and −4.6, respectively, vs −2.7 for placebo; p < 0.001 for both comparisons). Patients treated with galcanezumab had greater response rates and greater reductions in the number of monthly MHDs requiring acute medication compared with placebo-treated patients.

Galcanezumab-treated patients again had a greater improvement in functioning (as measured by the MSQ Role Function-Restrictive domain score) compared with placebo-treated patients, beginning at month 1. More patients treated with galcanezumab achieved clinically meaningful levels of improvement in functioning (responder rate based on MSQ Role Function Restrictive domain) compared with those treated with placebo. The 120mg dose was associated with a significant reduction in disability over placebo.

Long term efficacy

Efficacy was sustained for up to 1 year in an open-label study in which patients with either episodic or chronic migraine (with an average baseline of 10.6 monthly MHDs) received galcanezumab 120mg monthly (with an initial loading dose of 240mg for the first month) or galcanezumab 240mg monthly.

Among the 77.8% of patients completing the treatment period, the overall mean reduction from baseline in the number of monthly MHDs averaged over the treatment phase was 5.6 days for the 120mg dose group and 6.5 days for the 240mg dose group. Over 72% of patients completing the study reported a 50% reduction in MHDs at month 12. 

Safety and tolerability

In clinical trials the most commonly reported adverse drug reactions to galcanezumab were injection site reactions, vertigo, constipation, pruritus and urticaria. Most of the reactions were mild or moderate in severity and less than 2.5% of patients discontinued treatment as a result of adverse events.

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