Existing treatments for migraines are not always effective. Credit: Fuse/Thinkstock

In June, Teva of Petach Tikva, Israel, paid $200 million in cash and $625 million in future milestones to acquire Labrys Biologics of San Mateo, California. The Israeli drug maker wanted to get its hands on LBR-101, the biotech's preventive treatment for migraines and its only asset. LBR-101, a humanized monoclonal antibody (mAb) that binds and blocks calcitonin gene-related peptide (CGRP), is currently in phase 2b trials for chronic and high-frequency episodic migraines. Also pursuing anti-CGRP antibodies for migraine are Amgen, Arteus and Alder, which is working with Eli Lilly, indicating that companies have finally worked out how to effectively and safely hit this target, long considered a viable mechanism for migraine treatment.

Companies have blockbuster hopes for anti-CGRP blockers. About 1–2% of the population experiences some form of chronic headache, and existing treatments for migraine are not always well tolerated or effective. Anti-CGRPs offer a novel solution, although CGRP, a neuropeptide, has long been known to be active in the pathophysiology of migraine pain. During migraine attacks, CGRP in both central and peripheral nervous systems activates its receptors and facilitates the transmission of pain impulses. By blocking CGRP binding it is possible to stop transmission of pain signals leading to headaches.

We saw Labrys as the best-in-class opportunity

But toxicity has plagued the small-molecule CGRP antagonists developed so far. Telcagepant, developed by Whitehouse Station, New Jersey–based pharma Merck, was pulled in late-stage clinical trials after it caused liver failure. Lars Edvinsson, professor in internal medicine at Lund University, Sweden, says that he hasn't seen signs of liver toxicity with anti-CGRP antibodies, possibly because monoclonal antibodies are not broken down in the liver. Edvinsson worked on LBR-101 with originator Rinat Neuroscience.

A possible drawback to treating migraine with monoclonal antibodies is that they do not cross the blood-brain barrier. This may restrict the use of LBR-101 as an acute medication, but could work for prevention. Systemically administered CGRP has been shown to trigger headaches; and because anti-CGRP antibodies bind and neutralize free CGRP in the periphery, they could prevent the development of migraine. LBR-101 is administered as a single, monthly, subcutaneous injection, an attractive preventive measure for people who experience frequent headache episodes.

Other players pursuing anti-CGRP monoclonal antibodies are Alder Biopharmaceuticals of Bothell, Washington, testing ALD-403; Amgen of Thousand Oaks, California, developing AMG 334 I and Arteaus Therapeutics, of Cambridge, Massachusetts, which is working with Eli Lilly on LY2951742. All the candidates are in phase 2 trials.

“We saw Labrys as the best-in-class opportunity,” says Nina Kjellson of Menlo Park, California–based venture capital company InterWest Partners, which was one of four key investors in the $31-million Labrys Biologics Series A funding in December 2012. Teva and Labrys were unable to comment due to the acquisition. “We have been waiting for a breakthrough in migraine since the triptans,” says Mark Weatherall, consultant neurologist at the London Headache Centre and Charing Cross Hospital, UK, who has not been involved in any of the studies. “These monoclonal antibodies are a vindication of 25–30 years work on this pathway.”