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CGRP doesn't trigger migraine, but it "dials up the volume" on headache pain. "It makes the nerve cells more sensitive to pain input. It's as if you have a radio and you turn the volume up and up and up," says Stephen Silberstein, MD, director of the Jefferson University Headache Center in Philadelphia. "If you block CGRP, you turn the volume down."

Following close on Aimovig's heels are three other drugs that target CGRP: fremanezumab, galcanezumab, and eptinezumab (which is given by IV).

  • Fremanezumab has completed phase III trials and is under review by the FDA to prevent migraine and cluster headaches. Approval is expected later this year.
  • Galcanezumab has finished phase III trials for episodic migraine prevention and is also being studied as a treatment for cluster headaches. Approval is also expected later this year.
  • Eptinezumab is in phase III trials. Its maker plans to submit an application with the FDA later this year. It is for chronic migraine prevention.

How Monoclonal Antibodies Prevent Migraine

While all of the drugs work on CGRP, they don’t all work the same way. Three of them target the CGRP molecule itself. Aimovig goes after CGRP's receptor in the brain.

"You can think of the CGRP molecule as a key that unlocks a door to activate a particular brain mechanism, and you can think of the receptor as the lock the key fits into," says Lipton, who's also the Edwin S. Lowe professor and vice chairman of neurology at Albert Einstein College of Medicine. It's possible that if a CGRP-targeting drug doesn't work for someone, a drug that targets the receptor might, he says.

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