Experimental Agent Boosts Hope for Monoclonal Antibody Treatment of Migraine

Once researchers were able to isolate CGRP, experiments were conducted in which the peptide was injected into human volunteers. If the volunteers had a history of migraine, the investigators found that all of the subjects would develop a migraine attack within one to two hours. “The CGRP therapy, if you inject peripherally, does not cross the blood-brain barrier, does not enter the brain,” Dr. Bigal said. “They were inducing migraine, full-blown migraine, without ever getting into the brain. And if they injected CGRP therapy in nonmigraineurs, [the subjects] would not develop migraine. They would develop some sort of mild, nonspecific pain.”

From there, it was a short leap to the concept of developing CGRP receptor antagonists, and companies such as Merck and Boehringer Ingelheim developed agents—all of which failed to reach market despite proven efficacy. “To my knowledge, there has never been a CGRP receptor antagonist that got into efficacy studies that failed on efficacy,” Dr. Bigal said. “Nonetheless, we still do not have a CGRP [drug] approved for migraine therapy because we were never able to manage the safety … in this small-molecule scenario. And that’s why we are switching to antibodies.”

Besides Labrys, three companies—Amgen, Alder Biopharmaceuticals, and Eli Lilly (owing to its recent acquisition from Arteaus Therapeutics)—are developing their own anti-CGRP monoclonal antibodies, each of which is in phase IIa or IIb trials. Dr. Bigal reported that Labrys has initiated two phase IIb studies—one testing two doses of medication for the prevention of chronic migraine, the other testing two different doses for high-frequency episodic migraine.

“If we succeed, we’re going to have top-line data by the end of the year or early next year ... from a phase IIb perspective,” he said. “We’re going to be starting phase III in a dual environment for high-frequency and for chronic migraine.”

—Fred Balzac