Clinical Trials

Date: 2018-06-27

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the American Headache Society (AHS) annual meeting

Company: Eli Lilly (USA - IN)

Product: Emgality™ (galcanezumab-gnlm - LY2951742)

Action mechanism:

monoclonal antibody. Galcanezumab (LY2951742) is a once-monthly subcutaneously injected calcitonin gene-related peptide (CGRP) antibody currently being studied as a potential treatment for the prevention of chronic and episodic migraine and cluster headache. Lilly\'s CGRP antibody is a biologic entity that binds and inhibits the activity of CGRP, a sensory neuropeptide thought to be associated with vasodilation, pro-inflammatory effects and pain signaling, all thought to be implicated in the pathophysiology of migraine and cluster headache.

Disease: episodic migraine, chronic migraine

Therapeutic area: CNS diseases - Neurological diseases

Country: Canada, Puerto Rico, USA (EVOLVE-1) Brazil, Czech Republic (EVOLVE-2) Brazil, Czech Republic, Republic of Korea (REGAIN)

Trial details:

EVOLVE-1 (NCT02614183) and EVOLVE-2 (NCT02614196) are six-month Phase 3, randomized, double-blind, placebo-controlled global trials evaluating the safety and efficacy of two doses of galcanezumab administered subcutaneously (120 mg or 240 mg once-monthly, following a 240 mg starting dose) compared with placebo in 1,773 patients with episodic migraine (858 patients in EVOLVE-1 and 915 patients in EVOLVE-2). To be eligible for the trials, patients must have experienced between four and 14 migraine headache days per month. Patients that participated in these trials had an average of 9.1 migraine headache days per month at baseline. The primary endpoint was the mean change from baseline in monthly migraine headache days over the six-month, double-blind treatment phase.
REGAIN (NCT02614261) is a three-month Phase 3, randomized, double-blind, placebo-controlled global trial evaluating the safety and efficacy of two doses of galcanezumab administered subcutaneously (120 mg or 240 mg once-monthly, following a 240 mg starting dose) compared with placebo in 1,113 patients with chronic migraine. To be eligible for the trial, patients must have experienced at least 15 headache days per month, of which at least eight met criteria for migraine. Patients that participated in the trial had an average of 19.4 migraine headache days per month at baseline. The primary endpoint was the mean change from baseline in monthly migraine headache days over the three-month, double-blind treatment phase. In REGAIN, galcanezumab was further evaluated for an additional nine months of an open-label extension phase following the three-month, double-blind treatment phase.

Latest news:

• On June 27, 2018, Eli Lilly announced results from a post-hoc analysis which demonstrated efficacy of Emgality™ (galcanezumab-gnlm) in patients with episodic and chronic migraine who had previously failed preventive treatment with Botox® (onabotulinumtoxinA). Detailed results from a post-hoc analysis of three Phase 3 studies (EVOLVE-1, EVOLVE-2 and REGAIN) have been presented as a late-breaking presentation at the American Headache Society (AHS) annual meeting in San Francisco. This post-hoc analysis evaluated patients treated in the EVOLVE-1 and EVOLVE-2 studies for six months and the REGAIN study for three months. The post-hoc analysis reviewed the mean change from baseline in the number of monthly migraine headache days and the proportion of patients with at least a 50 percent reduction in number of monthly migraine headache days in patients who had previously failed Botox® due to lack of efficacy or tolerability issues, using integrated EVOLVE-1 and EVOLVE-2 results and REGAIN results.
In this subgroup analysis, patients treated with both doses of Emgality™ who previously failed preventive treatment with Botox® experienced a statistically significantly greater reduction in the average number of monthly migraine headache days, and a statistically significantly greater percent (at least a 50 percent) reduction in the number of migraine headache days, compared to patients treated with placebo.
Average reduction in monthly migraine headache days: 3.91 days for 120 mg and 5.27 days for 240 mg compared to 0.88 days for placebo, p?0.03 for both dosing groups compared with placebo.
Mean percentages of patients with at least 50 percent reduction in monthly migraine headache days: 41.3% for 120 mg and 47.5% for 240 mg compared to 9.4% for placebo, p?0.02 for both dosing groups compared with placebo. As previously reported in these Phase 3 studies, the most commonly-reported adverse events were injection site reactions.
In this integrated analysis of patients who had previously failed treatment with Botox®, patients treated with Emgality also had statistically significant improvements in quality of life, as measured by the Migraine-Specific Quality of Life Questionnaire (MSQ) and the Patient Global Impression of Severity (PGI-S) rating.
• On April 24, 2018, Eli Lilly announced results from a post-hoc subgroup analysis which demonstrated efficacy of galcanezumab in patients with episodic and chronic migraine who previously failed to respond to two or more preventive therapies. Detailed results from a new subgroup analysis of three Phase 3 studies (EVOLVE-1, EVOLVE-2 and REGAIN) evaluating galcanezumab have been presented as part of the "Best of Headache" platform session at the American Academy of Neurology (AAN) annual meeting in Los Angeles. As previously reported, in these Phase 3 studies, the most commonly-reported adverse events were injection site reactions.
In this subgroup analysis, patients treated with both doses of galcanezumab who previously failed two or more preventive therapies experienced a statistically significant reduction in the average number of monthly migraine headache days, and at least a 50 percent reduction in the number of migraine headache days, compared to patients treated with placebo. EVOLVE-1/ EVOLVE-2 (as evaluated over six months) for patients who failed at least 2 prior preventive medications (N=172):
Average reduction in monthly migraine headache days: 3.45 days for 120 mg and 3.85 days for 240 mg compared to 0.81 days for placebo, p<0.001 for both dosing groups compared with placebo.
Mean percentages of patients with at least 50 percent reduction in monthly migraine headache days: 54.6% for 120 mg and 61.2% for 240 mg compared to 26.2% for placebo, p<0.001 for both dosing groups compared with placebo. REGAIN (as evaluated over three months) for patients who failed at least 2 prior preventive medications (N=323): Average reduction in monthly migraine headache days: 5.91 days for 120 mg and 3.30 days for 240 mg compared to 1.44 days for placebo, p<0.01 for both dosing groups compared with placebo.
Mean percentages of patients with at least 50 percent reduction in monthly migraine headache days: 30.4% for 120 mg and 18.3% for 240 mg compared to 9.7% for placebo, p<0.05 for both dosing groups compared with placebo. Galcanezumab represents the first of three investigational, non-opioid treatments in development as part of Lilly's overall pain portfolio. The portfolio also includes lasmiditan for the acute treatment of migraine and tanezumab, developed in partnership with Pfizer, for the treatment of osteoarthritis pain, chronic low back pain and cancer pain.
• On June 10, 2017, Eli Lilly announced positive results from three Phase 3 studies of galcanezumab, an investigational treatment for the prevention of episodic and chronic migraine, including late-breaking data on several key secondary endpoints for galcanezumab compared to placebo at both studied doses. Detailed results from these studies (EVOLVE-1, EVOLVE-2 and REGAIN) have been presented at the American Headache Society (AHS) annual scientific meeting in Boston. Based on these results, Lilly will submit a Biologics License Application to the FDA for galcanezumab in the second half of 2017, followed by submissions to other regulatory agencies around the world.
EVOLVE-1 and EVOLVE-2 Study Results: In both studies, over the six-month treatment period, patients with episodic migraine treated with galcanezumab 120 mg and 240 mg doses experienced a statistically significantly greater decrease in the average number of monthly migraine headache days compared to patients treated with placebo, with statistically significant improvements observed at each month starting at one month of treatment. A statistically significantly greater percentage of patients treated with both doses of galcanezumab achieved at least a 50 percent, 75 percent and 100 percent reduction in the number of migraine headache days compared to placebo over the six-month treatment period, in both studies after multiplicity adjustment.
EVOLVE-1: – At least a 50 percent reduction: 62.3% for 120 mg and 60.9% for 240 mg compared to 38.6% for placebo, p < 0.001 for both dosing groups
– At least a 75 percent reduction: 38.8% for 120 mg and 38.5% for 240 mg compared to 19.3% for placebo, p < 0.001 for both dosing groups
– 100 percent reduction: 15.6% for 120 mg and 14.6% for 240 mg compared to 6.2% for placebo, p < 0.001 for both dosing groups EVOLVE-2: – At least a 50 percent reduction: 59.3% for 120 mg and 56.5% for 240 mg compared to 36.0% for placebo, p < 0.001 for both dosing groups
– At least a 75 percent reduction: 33.5% for 120 mg and 34.3% for 240 mg compared to 17.8% for placebo, p < 0.001 for both dosing groups
– 100 percent reduction: 11.5% for 120 mg and 13.8% for 240 mg compared to 5.7% for placebo, p < 0.001 for both dosing groups Patients treated with galcanezumab in both studies also had a statistically significantly greater reduction of monthly migraine headache days with acute medication use compared to placebo over the six-month treatment period after multiplicity adjustment.
EVOLVE-1: An average reduction of 4.0 days for 120 mg and 3.8 days for 240 mg compared to 2.15 days for placebo, p < 0.001 for both dosing groups EVOLVE-2: An average reduction of 3.7 days for 120 mg and 3.6 days for 240 mg compared to 1.85 days for placebo, p < 0.001 for both dosing groups
Patients treated with both doses of galcanezumab also saw statistically significant improvement in physical function compared to placebo over the six-month treatment period, as measured by both the Role Function-Restrictive (RF-R) domain score of the Migraine-Specific Quality of Life Questionnaire (MSQ) and the Patient Global Impression of Severity (PGI-S) rating after multiplicity adjustment.
REGAIN Study Results: Over the three-month treatment period, patients with chronic migraine treated with galcanezumab 120 mg and 240 mg doses experienced a statistically significantly greater decrease in the average number of monthly migraine headache days compared to patients treated with placebo. Statistically significant improvements for both doses of galcanezumab were observed at each month starting at one month of treatment.
A statistically significantly greater percentage of patients also achieved at least a 50 percent reduction in the number of migraine headache days compared to placebo over the three-month treatment period (27.6% for 120 mg and 27.5% for 240 mg compared to 15.4% for placebo, p < 0.001 for both dosing groups) after multiplicity adjustment.
Compared with placebo over the three-month treatment period, a statistically significantly higher percentage of patients treated with the 240 mg dose of galcanezumab achieved at least a 75 percent reduction in the number of migraine headache days (8.8% compared to 4.5% for placebo, p < 0.001) after multiplicity adjustment. Patients treated with the 240 mg dose of galcanezumab also achieved a statistically significantly greater reduction in the number of monthly migraine headache days with acute medication use compared to placebo over the three-month treatment period (an average of 4.3 days compared to 2.2 days for placebo, p < 0.001) after multiplicity adjustment.
Patients treated with 240 mg of galcanezumab also saw statistically significant improvement in physical function compared to placebo over the three-month treatment period, as measured by both the RF-R domain score of the MSQ and PGI-S rating after multiplicity adjustment.

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