FDA Approves Second Anti-CGRP Treatment for Migraine

New class of therapy designed specifically for migraine prevention, approved by FDA

In more groundbreaking news for the migraine community, the FDA just approved the second of a new class of drugs specifically designed to prevent migraine. Fremanezumab-vfrm (AJOVY™) comes on the heels of erenumab (Aimovig™), approved in May 2018. While both treatments zero in on the same molecular pathway, their target is different (protein versus the protein’s receptor). The good news is that both are effective and carry a low incidence of side effects.

“This is an unprecedented time for people living with Migraine,” says Dr. David Dodick, Chair of the American Migraine Foundation and neurologist at the Mayo Clinic. “This new class of therapy is designed specifically for migraine, reducing the frequency and severity of its expression, rather than chasing individual attacks.”

Fremanezumab may be administered subcutaneously monthly or every 3 months (quarterly). This is a far cry from the convention, up until now, of patients having to take a pill once, twice or even three times daily.

“Since the development of the anti-CGRP treatment class, for the first time, migraine patients have access to medication specifically designed to prevent migraine,” says Nim Lalvani, Director of the American Migraine Foundation. “Those living with migraine have hope for leading a life that is less dramatically impacted by this truly disabling disease.”

It’s important to highlight that while not all patients will respond to this class of treatment, a significant proportion do, at least over the first 3-6 months in clinical trials, and for these patients, their quality of life will improve.

“For those that don’t respond, the pipeline of alternative treatments with different targets is promising, and there is every reason to be very hopeful,” says Dr. Dodick.

So how do they work?

These drugs work by targeting calcitonin gene-related peptide (CGRP), a neuropeptide known to be involved in pathogenesis of a migraine attack.

“When CGRP is released, it is believed to drive pain signaling within the trigeminal sensory nerve resulting in the headache of a migraine attack,” says Dr. Stewart Tepper, a professor of Neurology at the Geisel School of Medicine at Dartmouth and Director of the Dartmouth Headache Center at the Dartmouth-Hitchcock Medical Center.

The new treatments are comprised of monoclonal antibodies that work against CGRP or the receptor to which CGRP binds. These monoclonal antibodies are large molecules, do not cross into the brain to any significant degree, and are not metabolized by the liver. That means off-target organ toxicity and interactions with other drugs should be minimal, and thus far, the side effect profile overall appears comparable to placebo.

In monoclonal antibody clinical trials, the reduction in days lived with migraine was significantly reduced, the proportion of patients experiencing a more than 50% response was substantial, and the onset of effect in some patients occurs within four weeks—even as early as one week in some.

Even in those who don’t experience a significant response within one month, a proportion will experience a response in the subsequent 1-2 months (Read more about the specifics of anti-CGRP treatments here.)

“The American Migraine Foundation will continue to work alongside the migraine community to ensure they have the tools and resources they need to start those vital conversations with their healthcare providers to determine whether these treatments are right for them,” says Lalvani.

This is a pivotal time in migraine research and treatment, but there is always more that can be done to serve those living with migraine. The American Headache Society and the American Migraine Foundation will continue to focus our attention on initiatives that advance research and knowledge while improving the lives and care of those with migraine and other severe headache disorders.