Lilly Announces Post-Hoc Analyses of Emgality Phase 3 Trials Demonstrating Significant Improvements in Daily Functioning and Reduction in Disability for Migraine Patients

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Recently, Eli Lilly presented post-hoc analysis data from the pivotal Phase III clinical program of the migraine medication Emgality (galcanezumab-gnlm) at the 61st Annual Scientific Meeting of the American Headache Society. The results demonstrated that treatment with Emgality improved daily functioning and delayed disability progression in patients with chronic migraine and episodic migraine.

Migraine is the second leading cause of disability in the United States and can significantly impact patients’ lives. Treatment with Emgality can effectively reduce the number of migraine days per month. Given the various disabilities and functional limitations caused by migraines, it is crucial to determine whether pharmacological treatments such as Emgality can improve migraine-related disability and alleviate restrictions on daily activities, relationships, productivity, and leisure time.

The post hoc analysis was based on data from three double-blind, placebo-controlled Phase III clinical studies evaluating Emgality for the treatment of chronic migraine (the REGAIN study) and episodic migraine (the EVOLVE-1 and EVOLVE-2 studies). The specific data are as follows:

(1) Based on the results from the Migraine Disability Assessment (MIDAS) questionnaire, a significantly higher proportion of patients treated with Emgality showed a reduction in migraine-related disability compared to those receiving placebo. The questionnaire assessed headache-related disability by measuring time lost from work, study, household chores, and non-work activities due to headaches, with disability categories corresponding to varying degrees of functional limitation and healthcare needs.

(2) In the REGAIN study, after 3 months of treatment, the proportion of patients achieving “little or no disability” was significantly increased by 46.2% in the Emgality group compared with the placebo group (20.3% vs. 13.9%), regardless of baseline disability classification.

(3) In the pooled analysis of the EVOLVE-1 and EVOLVE-2 studies, patients with baseline disability severity classified as “moderate to very severe disability” were 66.1% more likely (44.0% vs. 26.5%) to transition to “mild/no disability” after 6 months of treatment with Emgality compared with placebo, with a statistically significant difference between the two groups.

(4) Compared with placebo, treatment with Emgality was associated with improvements in all seven items of the Role Function-Restrictions (RFR) domain of the Migraine-Specific Quality of Life Questionnaire (MSQ). The MSQ-RFR assesses the extent to which migraine restricts an individual’s daily social and work-related activities, including: feeling more energetic; experiencing less fatigue during work or daily activities; being able to concentrate better on work/daily activities; accomplishing more at work and at home; encountering less difficulty in carrying out work/daily activities; experiencing less interference with leisure activities; and experiencing less interference with interactions with family and friends.

(5) In the REGAIN study, compared with placebo, patients treated with Emgality showed greater improvement in daily functioning across all items of the MSQ-RFR, with differences reaching statistical significance for most items.

(6) In the pooled analysis of the EVOLVE-1 and EVOLVE-2 studies, patients in the Emgality treatment group demonstrated significantly greater improvements in daily functioning across all 7 items of the MSQ-RFR compared to those in the placebo group.

Overall, patients treated with Emgality for the prevention of chronic migraine or episodic migraine demonstrated improvements in migraine-related disability and function, as measured by migraine-specific limitations in daily activities.

Emgality is a monoclonal antibody that selectively binds to calcitonin gene-related peptide (CGRP). CGRP is a neuropeptide that has been shown to be released during migraine attacks and is considered a trigger for migraine episodes. Currently, CGRP and its receptor have become hot targets for the development of migraine medications.

In the United States and the European Union, Emgality was approved in September and November 2018, respectively, for the preventive treatment of migraine in adult patients. This June, Emgality received additional approval from the U.S. FDA for the treatment of episodic cluster headache (ECH) in adults to reduce attack frequency. With this approval, Emgality has become the first and only medication indicated for the treatment of ECH, as well as the first and only CGRP antibody therapy approved by the FDA for two distinct headache disorders.

To date, three antibody-based migraine drugs targeting CGRP and its receptor have been launched, with the other two being Novartis/Amgen’s Aimovig and Teva’s Ajovy. Both Emgality and Aimovig are administered via subcutaneous injection once monthly, while Ajovy can be administered via subcutaneous injection either once monthly or once every three months. Additionally, Alder BioPharmaceuticals’ eptinezumab is under review in the United States; this drug is administered via intravenous infusion once every three months.

Several other companies are developing oral CGRP receptor antagonists, including Allergan’s ubrogepant and Biohaven’s rimegepant. Both drugs are currently under regulatory review in the United States, with ubrogepant expected to receive a decision in the fourth quarter of this year. However, Biohaven has used a priority review voucher purchased for $105 million to accelerate the review of rimegepant. It remains to be seen which company will emerge as the first to market an oral CGRP receptor antagonist.

Reference Source: AHS 2019: Post-Hoc Analyses of Phase 3 Pivotal Studies of Emgality^® (galcanezumab-gnlm) Show Improvements in Daily Functioning and Reductions in Disability in Patients with Chronic and Episodic Migraine