BOSTON – Two phase III trials of the investigational monoclonal antibody erenumab show promising results in reducing – but not eliminating – days affected by migraines and related disruptions in daily life with limited side effects, representing “an entirely new way forward” in migraine prevention, according to Peter Goadsby, MD.
In May, shortly after the results were released at the annual meeting of the American Academy of Neurology, Amgen filed regulatory documents for erenumab with the Food and Drug Administration.
Erenumab, also known as AMG 334, “is going to be the first mechanism-specific, migraine-targeted preventive treatment approach ever,” Dr. Goadsby, a University of California, San Francisco, neurologist, predicted at the annual meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that is designed to block the calcitonin gene-related peptide (CGRP) receptor, which is linked to migraine.
Several drug makers are investigating CGRP-modulating treatments for migraine. Results suggest that the medications are “effective for episodic and migraine patients,” said Amaal Starling, MD, of the Mayo Clinic, Scottsdale, Ariz., who spoke about the drugs in a plenary session at the meeting. “They have rapid onset of efficacy, minimal side effects, and infrequent administration. All of these things may improve adherence.”
Dr. Goadsby is the lead author of the study reporting phase III results from the 24-week STRIVE trial, which tested two monthly subcutaneous doses of erenumab (70 mg and 140 mg) against placebo in a 1:1:1 ratio in 955 patients. The patients all had suffered from episodic migraine for at least a year.
“STRIVE has shown that the 70-mg and 140-mg doses are better than placebo at the regulatory endpoint and clinically relevant endpoints,” Dr. Goadsby said, “and there are improvements in function, everyday activities, and physical impairment. The overall frequency of adverse and serious events were comparable, even the same.”
The participants reported an average of 8.3 monthly migraine days (MMDs) at the beginning of the study. At the end, the number declined significantly by an average of 3.2 days (70-mg dose), 3.7 days (140-mg dose), and 1.8 days (placebo; P less than .001).
Half of those in the 140-mg group achieved at least a 50% reduction in MMDs, compared with 43% and 27% for the 70-mg and placebo groups, respectively (P less than .001).
The researchers also examined changes in scores regarding Physical Impairment (PI) and Impact on Everyday Activities (EA) as determined by the Migraine Physical Function Impact Diary. PI scores improved by 4.2, 4.8, and 2.4 points in the 70-mg, 140-mg, and placebo groups, respectively. EA scores improved by 5.5, 5.9, and 3.3 points, respectively (P less than .001).
The study authors reported that tolerability was similar for placebo and the drug. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and sinusitis.
The researchers at the AAN meeting also released the results of a second study known as ARISE, led by David W. Dodick, MD, of the Mayo Clinic, Phoenix, Ariz. This double-blind, 12-week trial randomly assigned 577 adults with episodic migraine to a monthly subcutaneous dose of a placebo or 70 mg of erenumab.
The patients reported an average of 8.3 MMDs at the beginning of the trial. Those who took the medication reported an average 2.9 fewer MMDs while those who took the placebo reported 1.8 fewer MMDs (P less than .001) at 9-12 weeks.
Forty percent of those who took the drug saw a decrease of at least half in MMDs, compared with 30% of those who took placebo (odds ratio, 1.6; P = .010).
The PI levels declined by at least 5 points in 27% of placebo patients and 33% of erenumab patients (P = .13). EA levels declined by at least 5 points in 36% of placebo patients and 40% of erenumab patients (P = .26)
There were similar levels of adverse events in both drug and placebo groups, led by upper respiratory tract infection, injection site pain, and nasopharyngitis.
The Mayo Clinic’s Dr. Starling said anti-CGRP medications may dramatically improve the world of preventive migraine treatments, which are recommended for a third of migraine patients. Only about 3%-13% use them, she said.
In the future, it may be possible to be able to identify and target “super-responders” whose MMDs dip by 75% or more in some cases.
But there are questions, she said. The drugs’ specific mechanism for blocking migraine is not yet clear, and it’s also not clear if the CGRP antagonists could push patients at risk of TIA or cardiac angina to have a stroke instead.
Dr. Starling discussed some of the implications of the CGRP antagonists in development in a video interview.
Both studies were funded by Amgen. Dr. Goadsby reported numerous grants and personal fees from multiple drug makers, including Amgen. Dr. Starling reported support from Amgen, eNeura, and Eli Lilly. Dr. Dodick disclosed many relationships with pharmaceutical companies developing or marketing drugs for headache and migraine, including Amgen.