Summary: An immunotherapy that acts against an inflammatory molecule associated with migraines, has been shown to be successful in reducing the number of headaches people with chronic migraines suffer each month.
Source: Thomas Jefferson University.
A new study of fremanezumab, an immunotherapy that counteracts one of the molecules released during migraine, was found successful in reducing the number of days that chronic migraine sufferers experienced headaches. The results of the phase III clinical trial were published November 29, 2017 in the New England Journal of Medicine.
The World Health Organization estimates that between 127 and 300 million people around the world experience chronic migraine, defined as 15 or more headaches per month for at least three months. The disease can be debilitating and although a number of interventions exist, many only work for a certain time before they fail to prevent or relieve pain.
“This therapeutic approach offers new hope for people whose migraines cannot be treated with existing medicine,” says Stephen D. Silberstein, M.D., principal investigator of the HALO CM trial, Professor of Neurology and Director of the Jefferson Headache Center at the Vicki & Jack Farber Institute for Neuroscience at Thomas Jefferson University Hospital. “Our worldwide effort to evaluate this novel therapeutic approach has shown positive results and was safe in patients.”
Fremanezumab, a monocolonal antibody developed by Teva Pharmaceuticals, is a biological agent that binds to and blocks the action of a migraine-associated protein called calcitonin gene-related peptide (CGRP). Mounting evidence of its importance in migraines has made CGRP a focal point of research and drug development. The peptide is released at high levels during migraine in response to inflammation, and triggers a cascade effect that stimulates more CGRP release. This results in increasing sensitivity of the brain to pain. By blocking this peptide, doctors hope to break the cycle of increasing inflammation and increased pain sensitivity that contributes to migraine headaches.
Researchers from 132 sites across nine countries enrolled 1130 patients and randomly assigned them to one of three groups: one that received quarterly treatments, a group that received one treatment per month, and one that received placebo injections. The trial lasted for 16 weeks, with a 12-week treatment window.
The results of the trial show that treatment with fremanezumab reduced the number of days patients experience headache by an average of 4.3 days with quarterly treatment and 4.6 days with monthly treatment. “We saw some patients with 100 percent reduction in migraine, others with 75 percent reduction,” says Dr. Silberstein. The level of response varied between patients.
The researchers also looked at how well the therapy worked relative to each patient’s headache burden. They calculated the percent of patients who had more than a 50 percent reduction in the number of days they experienced either a severe or moderate headache per month. Using this measure, the researchers saw that 37.6 percent of patients on the monthly regimen, and 40.8 percent on the quarterly regimen had at least a 50 percent reduction in the number of moderate headaches per month, compared to 18.1 percent in the placebo group.
The therapy had a favorable safety profile with the most common adverse event reported as irritation at injection site, which was reported in the placebo group as well.
“If approved, this treatment would provide physicians with an important new tool to help prevent migraine, reduce a patient’s migraine load, and potentially help patients return to normal” says Dr. Silberstein.
Funding: This study was funded by Teva Pharmaceuticals, ClinicalTrials.gov number NCT02621931. A complete list of potential conflicts of interest can be found in the manuscript.
Source: Edyta Zielinska – Thomas Jefferson University
Publisher: Organized by NeuroscienceNews.com.
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Original Research: Abstract for “Fremanezumab for the Preventive Treatment of Chronic Migraine” by Stephen D. Silberstein, M.D., David W. Dodick, M.D., Marcelo E. Bigal, M.D., Ph.D., Paul P. Yeung, M.D., M.P.H., Peter J. Goadsby, M.D., Ph.D., Tricia Blankenbiller, M.A., Melissa Grozinski-Wolff, B.S., Ronghua Yang, Ph.D., Yuju Ma, M.S., and Ernesto Aycardi, M.D. in New England Journal of Medicine. Published online November 30 2017 doi:10.1056/NEJMoa1709038
[cbtabs][cbtab title=”MLA”]Thomas Jefferson University “Phase III Immunotherapy Trial For Migraine Shows Promising Results.” NeuroscienceNews. NeuroscienceNews, 30 November 2017.
<https://neurosciencenews.com/immunotherapy-migraine-8076/>.[/cbtab][cbtab title=”APA”]Thomas Jefferson University (2017, November 30). Phase III Immunotherapy Trial For Migraine Shows Promising Results. NeuroscienceNews. Retrieved November 30, 2017 from https://neurosciencenews.com/immunotherapy-migraine-8076/[/cbtab][cbtab title=”Chicago”]Thomas Jefferson University “Phase III Immunotherapy Trial For Migraine Shows Promising Results.” https://neurosciencenews.com/immunotherapy-migraine-8076/ (accessed November 30, 2017).[/cbtab][/cbtabs]
Abstract
Fremanezumab for the Preventive Treatment of Chronic Migraine
BACKGROUND
Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene–related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine.
METHODS
In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine–specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose.
RESULTS
Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the average number of headache days per month was 4.3±0.3 with fremanezumab quarterly, 4.6±0.3 with fremanezumab monthly, and 2.5±0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each fremanezumab group (1%) and 3 patients in the placebo group (<1%).
CONCLUSIONS
Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT02621931.)
“Fremanezumab for the Preventive Treatment of Chronic Migraine” by Stephen D. Silberstein, M.D., David W. Dodick, M.D., Marcelo E. Bigal, M.D., Ph.D., Paul P. Yeung, M.D., M.P.H., Peter J. Goadsby, M.D., Ph.D., Tricia Blankenbiller, M.A., Melissa Grozinski-Wolff, B.S., Ronghua Yang, Ph.D., Yuju Ma, M.S., and Ernesto Aycardi, M.D. in New England Journal of Medicine. Published online November 30 2017 doi:10.1056/NEJMoa1709038
