Potential Drug LY2951742 to Prevent Migraines?

Internal Medicine World Report, September 2014,

Physicians have few effective weapons to treat a migraine, an ailment that accounts for more than half of disability with a neurological cause. Chronic migraine is said to affect 2% of the world's population.

Physicians have few effective weapons to treat a migraine, an ailment that accounts for more than half of disability with a neurological cause. Chronic migraine is said to affect 2% of the world’s population.

In a report in The Lancet, David Dodick, MD and colleagues track the effectiveness of LY2951742 in preventing migraine. Dodick is a professor in department of neurology at the Mayo Clinic in Phoenix, Arizona. The team reported on the results of a Phase 2 trial, registered at Clinical Trials.gov as NCT01625988. No serious adverse events were attributed to the drug.

The drug LY2951742 is a monoclonal antibody to calcitonin gene-relate peptide, and the research appears to show this peptide plays a role in the pathogenesis of migraines. The study looked at 227 patients who either got LY2951742 (107 patients) or placebo (110). Over a 12-week period, the group getting the drug reported 4.2 fewer days of headache and the placebo group reported 3.0 fewer headache days. In each group 13 patients either dropped out or were lost to follow-up.

Dodick and colleagues concluded that LY2951742 “might be beneficial in migraine prevention and provide support for the role of calcitonin gene-related peptide (CGRP) antibodies for the preventive treatment of migraine.”

The study subjects were men and women ages 18 to 65 with a history of migraines. They got 150 mg by subcutaneous injection once every 2 weeks for 12 weeks. All were patients who had between 4 and 14 migraine headaches a month.

Though the placebo response rate was high, “exaggerated placebo response rates in migraine treatment trials are well known and the high rates in this trial might be due in part to the heightened expectations of patients being enrolled into a trial with a new compound developed specifically for migraine prevention,” Dodick wrote. But he said that the fact that the group receiving the drug had an increased response rate was significant.

Exactly how LY2951742 may work is unclear. “Blocking CGRP-induced neurogenic vasodilation or inhibition of central trigeminal nociceptive pathways are each possible sites and mechanisms of action,” commented Dodick. He was also not sure whether LY2951742 crossed the blood-brain barrier, which would be unusual for a monoclonal antibody. “The blood-brain barrier might be more permeable during migraine attacks ad there might be sufficient access to central sites of action,” he said.

He expressed hope that the drug will give patients relief, since “safe, effective, and well tolerated treatment for the prevention of migraine represents an enormous unmet medical need,” with current remedies showing too many adverse effects, modest efficacy, and because patients tend not to adhere to regimens involving them.

Dodick has served on advisory boards or consulted for 23 drug or medical devices companies. He also disclosed remuneration from 20 entities for editorial work, speaking fees, and travel fees. The study was funded by Arteaus Therapeutics, a company that has paid consulting fees to Dodick and one co-author and employs a third co-author.