Relief, in the form of a new drug, may be on the horizon for those who have tried in vain to prevent migraine with other treatments, a preliminary study suggests.
Novartis has announced full results from the Phase IIIb LIBERTY trial of Aimovig (erenumab, AMG 334) in episodic migraine patients who had previously failed two to four preventive treatments, due to lack of efficacy or intolerable side effects.
Erenumab, developed by Amgen, belongs to a new class of drugs called fully human monoclonal antibodies that work by blocking the calcitonin gene-related peptide (CGRP) receptor, which plays an important role in migraine activation. Erenumab occupies the nerves to which CGRP would usually bind.
Although low cost, over-the-counter drugs such as ibuprofen help many suffering from migraines, others must turn to stronger prescription medications, such as ergotamine or sumatriptan - these constrict brain blood vessels and are known to cause dizziness and nausea. For some, Botox injections are also used to ease migraines.
But there remains a large portion of sufferers that are not helped by any of these treatments.
“This is the first-ever mechanism specific migraine drug designed for prevention. This will change migraine treatment for those who don’t respond to conventional treatments,"
lead study author Dr. Peter Goadsby was quoted as saying by NBC News. Goadsby is professor of neurology at Kings College London, UK and University of California, San Francisco.
The LIBERTY study is the first to investigate a treatment targeting the CGRP pathway specifically in this challenging patient population. 246 patients who had experienced two to four previous preventive treatment failures were randomized to receive monthly subcutaneous injections of either erenumab 140mg or placebo for 12 weeks.
Patients taking erenumab had nearly three-fold higher odds of having their migraine days cut by at least 50%, with more than twice as many patients taking erenumab achieving this reduction compared to placebo (weeks 9-12: 30.3% with erenumab, 13.7% with placebo, p=0.002, odds ratio 2.73).
“The LIBERTY study distinctively demonstrates the ability of an anti-CGRP receptor antibody to significantly reduce migraine frequency and its associated burden in patients who could not find the relief they need with the currently available preventive treatment options. These compelling data offer new hope of fewer migraine days to those people with migraine who may have cycled through current standard of care unsuccessfully for years due to lack of efficacy and tolerability,"
said Prof. Uwe Reuter, Managing Medical Director at Charité Universitätsmedizin.
Erenumab Study Results
Patients taking erenumab also had statistically significant and clinically meaningful improvements from baseline compared to placebo across all secondary endpoints:
Reduction in monthly migraine days
Decrease in acute migraine-specific drug use
75% or greater reduction in monthly migraine days
100% reduction in monthly migraine days
Improved physical functioning and ability to complete everyday activities as measured by the Migraine Physical Function Impact Diary (MPFID) scales
Over 97% of erenumab patients completed the double-blind phase of the LIBERTY study. There were no adverse events leading to discontinuation of treatment in the erenumab group while 0.8% of those in the placebo group experienced adverse events leading to discontinuation of treatment.
The response rate was considered low, as only 30% of patients receiving the active drug achieved the 50% reduction in migraine days. But, said Reuter:
“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. That reduction in migraine headache frequency can greatly improve a person’s quality of life."
Potential problems relating to vascular conditions and unknown risks of monoclonal antibodies that affect CGRP raise questions that are yet to be answered.
“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. There was a cardiovascular death in a 52-year-old male participant in an interim analysis of a long-term open-label extension study of erenumab."
Elizabeth Loder, MD, MPH, of Brigham and Women’s Faulkner Hospital in Boston, said, speaking to MedPage Today.
Loder was not involved with the study.
Migraine is a distinct neurological disease. It involves recurrent attacks of moderate to severe head pain that is typically pulsating, often unilateral and associated with nausea, vomiting and sensitivity to light, sound and odors.
Migraine is associated with personal pain, disability and reduced quality of life, and financial cost to society. It has a profound and limiting impact on an individual’s abilities to carry out everyday tasks, and was declared by the World Health Organization to be one of the top 10 causes of years lived with disability for men and women.
It remains under-recognized and under-treated,. Existing preventive therapies have been repurposed from other indications and are often associated with poor tolerability and lack of efficacy, with high discontinuation rates among patients.
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 Emerging science abstract presented at AAN, 24 April 2018, Los Angeles
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