Dr. Eric Hastriter practices pediatric headache medicine in Mesa, Arizona. Dr. Hastriter studies, evaluates, diagnoses, and treats conditions that affect the nervous system, specifically relating to head pain. Headache specialist are trained to fully understand and treat such conditions as Chronic Migraine, Chronic Tension... more
Thursday, June 15, 2017
BY RICHARD ROBINSON
BOSTON—In patients with chronic migraine, the monoclonal antibody erenumab reduced monthly migraine days by 6.6 days, while a single injection of fremanezumab appeared to reduce migraine up to three months, according to abstracts presented here at the American Headache Society annual meeting held June 8-11.
Erenumab, which is being developed by Amgen, binds to the calcitonin gene-related peptide (CGRP) receptor, and is one of four monoclonals in development for migraine treatment targeting the CGRP system. The results of the trial were published this month in The Lancet Neurology.
To test the potential of erenumab in chronic migraine, defined as headache for 15 or more days per month, and migraine for eight or more days per month, investigators enrolled 667 patients, randomized 3:2:2 to monthly placebo, erenumab 70 mg, or erenumab 140 mg, administered subcutaneously. The primary endpoint was the change from baseline in monthly migraine days over three months of treatment. The researchers used the mean of the three months, rather than the reduction in the final month, because experience has shown that the response rate fluctuates somewhat from month to month, said the lead investigator, Stewart J. Tepper, MD, FAHS, professor of neurology at the Geisel School of Medicine at Dartmouth in Hanover, NH.
At baseline, patients in each group had a mean of 18 monthly migraine days. Both doses of erenumab reduced that by a mean of 6.6 days, versus 4.2 days for placebo (p<0.001 for both). Active treatment was also associated with a greater response rate: 40 percent and 41 percent in the low- and high-dose groups, respectively, experienced a 50 percent or greater reduction in monthly migraine days, versus 23 percent for placebo (p<0.001 for both). Adverse event profiles were similar for active treatment and placebo, except for a small increase in injection-site pain in those receiving erenumab.
Based on these results, and the results of previous trials in episodic migraine, the company has submitted data to the US Food and Drug Administration for an indication for both episodic and chronic migraine, Dr. Tepper said.
In a phase 3, randomized placebo-controlled study, a single injection of fremanezumab appeared to work within one week of administration and provided significant reduction in migraine for up to three months compared to placebo. A total of 1,130 patients were randomized to each of three arms: placebo injections once a month for three months; a single 675 mg subcutaneous injection of fremanezumab, followed by two monthly placebo injections; and one 675 mg injection of fremanezumab followed by two monthly injections of 225 mg fremanezumab. The primary endpoint was the change from baseline in the number of monthly headache days of at least moderate severity over three months.
Placebo-treated patients experienced an average of 2.5 fewer headache days per month during the study. Monthly headache days declined by 4.6 days in patients receiving monthly fremanezumab, and by 4.3 days in those receiving the single dose (both results p<0.001 versus placebo).
Active treatment was associated with at least a 50 percent reduction in headache days in 41 percent of those on monthly treatment and 38 percent of those on quarterly treatment, versus 18 percent on placebo (both results p<0.001 versus placebo), according to Ernesto Aycardi, MD, vice president and therapeutical area head of headache and migraine at Teva Pharmaceuticals, which is developing the drug.
Benefits emerged within one week of initial treatment, Dr. Aycardi noted. "This is unique for preventive treatment. Usually preventive treatment of migraine takes months to begin to have an effect."
Stephen D. Silberstein, MD, FAAN, professor of neurology and director of the Headache Center at Jefferson University Hospital at Thomas Jefferson University in Philadelphia, who was not involved in the trial, commented that the results of these trials and those of the other CGRP system monoclonals "are exciting. These are the first drugs in 20 years specifically designed to treat migraine."
While erenumab binds the receptor and is a fully human antibody, and the others bind CGRP and are humanized, "I would look at them all as a group," Dr. Silberstein said, adding that they are all effective and appear safe and tolerable.
Absent head-to-head studies, it is difficult to determine what nuances there may be between these drugs, he said. "Instead, the global message from these trials is that we have a new series of drugs that are powerful and effective, and have a side-effect profile similar to placebo. For one of the most disabling of disorders, which affects millions of people in their most productive years, this allows hope."
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Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: A randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017;16(6):425-434.