Studies of the first specific mechanism-based treatments may harken a new era of prevention.
Two new studies may harken an era of mechanism-based migraine prevention.
“These 2 phase 2 studies are the first to report a migraine preventive effect from an entirely novel mechanism, calcitonin gene-related peptide (CGRP) blockade. As such they are the first specific mechanism-based preventive treatments for migraine,” co-author of both studies, Peter Goadsby, MD, PhD, Professor of Neurology at the University of California, San Francisco, and King’s College London, told ConsultantLive before his presentation at the American Academy of Neurology annual meeting in Philadelphia.
CGRP is a key transmitter of the chemicals used by nerves and in the brain in the migraine process. This peptide has been thought to be important in migraine, but never have drugs been developed to target the protein specifically.
The first study evaluated the efficacy and safety of ALD403, a genetically engineered humanized anti-CGRP antibody. The randomized, double-blind, placebo-controlled trial involved 163 persons who had migraine from 6 to 14 days each month. They received a placebo or a single intravenous dose of 1000 mg ALD403 and then were monitored for 24 weeks.
Those who received the drug had an average of 5.6 fewer migraine days per month, a 66% decrease, compared with 4.6 fewer days per month for those who received a placebo, a 52% decrease. Of those who received the drug, 16% had no migraine days at 12 weeks; none of those who received the placebo were free from migraine at that point.
There were no differences in adverse effects between those receiving the drug and those receiving the placebo.
“These results support the conduct of larger randomized, placebo-controlled studies and may potentially represent a new era in disease-specific and mechanism-based preventive therapy for migraine,” said Dr Goadsby.
The second study evaluated the efficacy and safety of LY2951742, a fully humanized monoclonal antibody to CGRP. This randomized, double-blind, placebo-controlled trial included 217 persons who had migraine for 4 to 14 days each month. They received biweekly subcutaneous injections of a placebo or 150 mg of LY2951742 for 12 weeks.
Those who received the drug had an average of 4.2 fewer migraine days per month at 12 weeks, or a 63% decrease; those who received placebo had 3 fewer migraine days per month, or a 42% decrease.
Those who received the drug were more likely to have adverse effects, including pain at the injection site, upper respiratory tract infections, and abdominal pain. However, overall the drug was considered to be safe and well-tolerated, Dr Goadsby said, adding that the safety and robust efficacy results are promising and justify the conduct of larger, randomized, placebo-controlled, phase 3 studies.
Dr Goadsby said the patients who would be the best candidates for either of these 2 drugs are “those with troublesome episodic migraine, especially if they have failed more routine preventives or could not take them.”
He pointed out that there is a huge need because migraine remains poorly treated and there are few effective, well-tolerated, approved treatments that prevent attacks from occurring.
“We are seeing a truly generational change with the first mechanism-based preventive treatment for migraine,” Dr Goadsby concluded.