LOS ANGELES -- The calcitonin gene-related peptide (CGRP) receptor inhibitor erenumab (Aimovig) surpassed placebo in the phase IIIb LIBERTY trial of patients with episodic migraine for whom two to four previous preventive migraine treatments have failed, researchers reported here.
In the 12-week trial, patients who received erenumab were 2.7 times more likely to have reduced their migraine days by 50% or more than those treated with placebo, reported Uwe Reuter, MD, of the Charite University Medicine Berlin in Germany, and co-authors in from the to be held here next week.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Note that this randomized trial in patients with refractory migraine showed that the CGRP receptor inhibitor erenumab was more efficacious than placebo in terms of reducing migraine frequency by at least 50%.
- Overall response rates were low, with roughly 30% of erenumab-treated patients having at least a 50% reduction in migraine frequency.
By week 12, erenumab patients also had 1.6 fewer migraine days and 1.7 fewer acute migraine-specific medication days per month, on average, than placebo patients.
While the response rate was low -- only 30% of patients receiving the active drug achieved the 50% reduction in migraine days -- "the people we included in our study were considered more difficult to treat -- meaning that up to four other preventative treatments hadn't worked for them," Reuter said in a statement. "That reduction in migraine headache frequency can greatly improve a person's quality of life."
CGRP, a vasodilator found throughout the body, is elevated during a migraine attack. Erenumab, a fully humanized monoclonal antibody, blocks the CGRP receptor that may play a critical role in migraine.
The phase IIIb LIBERTY results add to previous episodic migraine prevention trials of erenumab like STRIVE and ARISE that were presented at last year's AAN meeting. Based on the clinical trials, there is no signal to date for any particular group of side effects up to 1 year of treatment, according to a representative from Novartis, the company that is co-developing erenumab with Amgen.
But questions about potential problems in critical vascular conditions and unknown risks of monoclonal antibodies that affect CGRP remain unanswered.
"The main worries have to do with the unknown long-term effects of CGRP suppression -- particularly concerns that this may increase the risk of ischemic stroke or myocardial infarction," said Elizabeth Loder, MD, MPH, of Brigham and Women's Faulkner Hospital in Boston, who was not involved with the study. "There was a cardiovascular death in a 52-year-old male participant in an of a long-term open-label extension study of erenumab."
"The safety of the antibodies in pregnancy also is unknown," Loder told 番茄社区 -- a particularly important matter since the burden of migraine is highest in . And besides the adverse events that can be anticipated with the known actions of CGRP, unknown side effects or safety concerns may emerge once the treatment is in widespread use, she added.
In this 12-week, double-blind study, Reuter and colleagues randomized 246 episodic migraine patients who had not responded to multiple therapies to receive injections of either 140 mg of erenumab or placebo once a month for 3 months. The primary endpoint was the proportion of patients achieving ≥50% reduction in mean monthly migraine days during weeks 9 through 12.
Of the 246 participants, 38.6% had not responded to two preventive medications, 37.8% had not responded to three, and 22.8% had not responded to four. Patients averaged 9.3 monthly migraine days and 4.6 monthly acute migraine-specific medication days at baseline.
At week 12, the proportion of patients achieving ≥50% reduction in migraines was higher in those treated with erenumab (30.3%) compared with placebo (13.7%) -- OR 2.73 (95% CI 1.43 to 5.19); P=0.002.
No patients in the erenumab group discontinued treatment because of adverse effects, and the safety and tolerability profile of the drug was similar to that of placebo, the researchers reported.
"Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief," Reuter said. "More research is now needed to understand who is most likely to benefit from this new treatment."
Limitations of the analysis, the researchers said, include its short time frame of 3 months. The trial includes an ongoing study, according to Novartis.
The phase III LIBERTY researchers will present their findings at the AAN meeting on Tuesday April 24, 2018, at 5:45 pm PT in the Concourse Hall 152/153 at the Los Angeles Convention Center.
Disclosures
This study was funded by Novartis Pharma.
Primary Source
American Academy of Neurology
Reuter U, et al "Efficacy and safety of erenumab in episodic migraine patients with 2–4 prior preventive treatment failures: Results from the Phase 3b LIBERTY study" AAN 2018.