Data from the EVOLVE-1 and EVOLVE-2 phase 3 clinical trials suggest that galcanezumab (Emgality, Eli Lilly) can maintain ≥50% responder rates equivalent to that of placebo while reducing more monthly migraine days for 5 months after halting treatment.
Virginia L. Stauffer, PharmD, clinical research scientist at Eli Lilly
Virginia L. Stauffer, PharmD
Patients with migraine who were treated with galcanezumab (Emgality, Eli Lilly) maintained a significant reduction in both monthly migraine days and migraine days that resulted in the need for acute medication for up to 5 months after treatment cessation, new study data show.1
The data, from the EVOLVE-1 and EVOLVE-2 phase 3 clinical trials, revealed that there were no statistically significant differences between the treatment groups and placebo groups for the time‐to‐first loss of ≥50% response. All told, the investigators, led by Virginia L. Stauffer, PharmD, found similar changes from baseline for the outcomes measured in the 2 studies.
“As expected, the galcanezumab treatment effects observed for migraine-relevant outcome measures during the treatment periods were reduced during the posttreatment periods,” Stauffer, a clinical research scientist at Eli Lilly, and colleagues detailed. “However, migraine-relevant outcomes did not return to baseline levels.”
Among the patients with ≥50% response at month 6, following treatment cessation, the number of patients losing this response rate increased. Five months posttreatment cessation (month 10), more than half of these patients had lost this response. As well, there were no significant differences between galcanezumab groups and placebo for time-to-first loss of response.
"This assessment was of interest because Emgality has an elimination half-life of 27 days, meaning its effect can persist after the last injection," Stauffer told NeurologyLive®. "The persistence of therapeutic effects is of interest to both patients and clinicians since migraine is a lifelong disease and preventive therapy may need to be stopped and started for various reasons."
In EVOLVE-1, the placebo group had 342 patients with ≥50% response, while the galcanezumab groups had 348 (120 mg, n = 177; 240 mg, n = 171) at month 6 (P ≤.001), while those numbers dropped to 320 and 326, respectively at month 10 (120 mg, n = 169; 240 mg, n = 157). Only the 120-mg group remained significant (P <.05). In EVOLVE-2, the treatment groups had 389 patients responding ≥50% (120 mg, n = 197; 240 mg, n = 192), while the placebo group had 382 at month 6 (P ≤.001). By month 10, those numbers had dropped to 353 for placebo and 377 for the galcanezumab arms (120 mg, n = 194; 240 mg, n = 183), with no significant differences.
“To our knowledge, EVOLVE-1 and EVOLVE-2 are the only phase 3 trials of anti-CGRP antibodies with a posttreatment period immediately following the double-blind treatment period. This provided the advantage of having a placebo comparator group during the 5 months in which patients were not receiving the active treatment,” Stauffer and colleagues wrote.
During the post-treatment periods, 1.6% (EVOLVE‐1; 12 of 739 patients) and 2.3% (EVOLVE‐2; 6 of 372 patients) of patients initiated migraine preventive treatments. In EVOLVE-1, the placebo group also had a rate of 1.6% (6 of 372), as did the individual dose groups (120 mg, 3 of 185; 240 mg, 3 of 182). In EVOLVE-2, the results were slightly lower for the 240- and 120-mg groups (1.4%) than placebo (3.2%).
In EVOLVE-1, the total change in monthly migraine headache days (MHDs) from pre-randomization baseline over the course of the 5 months was 1.1 (Standard Error [SE], 0.4) for the 120-mg dose and 1.5 (SE, 0.4) for the 240-mg dose, while placebo remained stable, only dropping 0.1 (SE, 0.3).
Likewise, the differences between the treatment groups and placebo were significant at each month in the timeframe for both the 120-mg group (Months 1‐6, P <.001; Month 7, P = .007; Month 8, P = .044; Month 9, P = .016; Month 10, P = .042) and the 240-mg group (Months 1—7, P <.001; Month 8, P = .015; Month 9, P = .021; Month 10, P = .238).
In EVOLVE-2, the reduction of monthly MHDs declined from 4.5 days (SE, 0.3) to 3.5 days (SE, 0.3) for the 120-mg dose, and 4.5 days (SE, 0.3) to 3.7 days (SE, 0.3) for the 240-mg dose. The placebo group’s reduction stayed at 2.8 days [SE, 0.2].
As in EVOLVE-1, the differences between the 120-mg and 240-mg groups and placebo in EVOLVE-2 were statistically significant throughout the entire study timeframe (P <.001). Additionally, the 120-mg dose was statistically significant at each month (Months 1—8, P <.001; Month 9, P = .002) with the only exception to this month-by-month significance at month 10 (P = .066). The 240-mg dose maintained statistical significance in all months compared to placebo (Months 1—7, P <.001; Month 8, P = .016; Month 9, P < .001; Month 10, P = .019).
In the phase 3 trials, galcanezumab was halted a month prior to the end of the treatment periods, allowing for time enough for 5 elimination half-lives by study end, Stauffer and colleagues estimated.
“This timeframe provides ample time to examine any treatment-related effects following treatment cessation and informs clinicians that the effects of galcanezumab do continue after cessation of treatment, which may be useful when treatment is stopped for a variety of reasons,” the investigators wrote.
1. Stauffer VL, Wang S, Voulgaropoulos M, Skljarevski V, Koviak A, Aurora SK. Effect of galcanezumab following treatment cessation in patients with migraine: results from 2 randomized phase 3 trials. Headache. Published online April 3, 2019. doi: 10.1111/head.13508.