Eli Lilly announce start of a PIV head-to-head study comparing galcanezumab-gnlm (120mg once-monthly with 240mg loading dose) with oral rimegepant 75mg taken every other day. The multi-site, randomised, double-blind, double-dummy, parallel-group study will include pts who meet the International Classification of Headache Disorders (ICHD) criteria for a diagnosis of episodic migraine with or without aura. The primary endpoint is 50% reduction in monthly migraine headache days and enrollment will begin later this year.
In a PIII study by Lily, galcanezumab met primary and all key secondary outcomes for efficacy and safety in patients with previous failures on two to four different standard-of-care migraine preventive medication categories. Galcanezumab cut the number of days patients experienced migraines per month by 4.1. The drug showed a 3.1-day improvement over placebo. 
Four CGRP inhibitors are in development - galcanezumab, erenumab, fremanezumab (TEV-48125) and eptinezumab (ALD403). Data presented at the American Headache Society conference indicates they offer similar activity, so their developers will have to rely on factors other than their clinical profiles if and when they come to market .
Results of EVOLVE-1 (NCT02614183) published in JAMA .
Lilly presents more detail from PIII studies. In EVOLVE-1 and EVOLVE-2, a 50% reduction was seen in around 60% of patients on galcanezumab versus 36%-39% of placebo users, with all migraine attacks eliminated in 12%-15% and 6%, respectively. Similarly, the REGAIN study in chronic migraine saw the drug hit the 50% reduction threshold in around 28% of patients, compared to 15% of the placebo group .
EVOLVE-1 & 2 and REGAIN are on-going but have all completed recruitment with completion expected Q2/3 17 .
In the two six-month PIII trials patients with episodic migraine treated with galcanezumab (120 mg or 240 mg) experienced a greater decrease in the number of monthly migraine headache days compared to those treated with placebo. In EVOLVE-1 there was a mean reduction of 4.7 days for 120 mg and 4.6 days for 240 mg compared to an average reduction of 2.8 days for placebo, (p < 0.001, both groups). In EVOLVE-2: there was a mean reduction of 4.3 days, 4.2 days for the two doses and 2.3 days for placebo (p < 0.001). In the REGAIN study the figures were 4.8, 4.6 and 2.7 days respectively .
PIII EVOLVE-2 study (NCT026141960 starts. The main purpose of this study is to evaluate the efficacy of LY2951742 in 825 adults with episodic migraine. Patients will be recruited in Argentina, Brazil, Czech Republic, Germany, Spain, UK, Israel, South Korea, Mexico, Netherlands, Taiwan & US. Collection of primary outcome data (change in number of monthly migraine headache days) is expected to complete in Jun 17 .
A PIII safety study (NCT02614287) begins, & will involve 250 adults. Collection of data should be complete Sep 17 .
PIII EVOLVE-1 study (NCT02614183) starts. The main purpose of this study is to evaluate the efficacy of LY2951742 in 825 participants with episodic migraine, recruited in the US & Canada. The primary outcome is change in number of monthly migraine headache days; collection of these data should complete Feb 17 .
PIII REGAIN study (NCT02614261) begins. The main purpose of this study is to evaluate the efficacy of LY2951742 in 825 adults with chronic migraine. Patients will be recruited in US, Argentina, Brazil, Canada, Czech Republic, Germany, Italy, UK, Israel, Mexico, Netherlands, Taiwan & Spain. Collection of primary outcome data (change in number of monthly migraine headache days) is expected to complete in Feb 17 .
LY2951742, a CGRP neutralizing antibody, for prevention of migraine met the primary endpoint in a PIIb study to prevent episodic migraine (4-14 headache days/month). The randomised, double-blind, placebo-controlled study (NCT02163993) evaluated the efficacy and safety of four doses of LY2951742 or placebo given in a once-monthly as a SC injection to 402 pts in the US with episodic migraine for 3 months. The study is objective was to assess superiority over placebo and the primary endpoint will be the mean change from baseline in the number of migraine days during the last 28-day period of the 3 month treatment phase. Eli Lilly and Company announced that LY2951742 met the primary endpoint in episodic migraine. LY2951742 demonstrated a statistically significant reduction in migraine headache days and a good safety and tolerability profile. Lilly will present data from this trial in a late-breaking session at the 57th Annual American Headache Society meeting on June 20th 2015. Full results are expected after August 2015 [1-3].