• Calcitonin gene-related peptides (CGRPs) are proteins that may contribute to migraine headache pain.
• New anti-CGRP drugs represent a new class of medications specifically developed for migraine prevention.
• Anti-CGRP drugs are expensive but promising, especially for people who cannot use other treatment options.

There are new developments in the world of treating migraine, a debilitating condition that affects millions of people in the U.S. and over 1 billion people worldwide. A new class of medications — drugs that target calcitonin gene-related peptides — has shown a lot of promise for treating the condition.

CGRPs are proteins found in the nervous system and are responsible for processing pain, increasing inflammation, and contributing to the development of migraine attacks. Medications that interfere with the activity of the body’s circulating CGRPs have been shown to be effective in reducing migraine attacks. These medications may be referred to as anti-CGRP medications or treatments, CGRP medications, or CGRP inhibitors.

Several members of MyMigraineTeam are unfamiliar with CGRP and anti-CGRP medications, and many are looking for answers. One member questioned, “Is anyone familiar with or has experience with the CGRP family of drugs?” Others have asked, “What are the CGRP injections?” and “Would you please tell me about other CGRP drugs available?

Continue reading for a closer look at the function of CGRP in the brain and body. We’ll discuss the role of CGRP in migraine and the different preventive treatment options that inhibit CGRP activity.

What’s Different About Anti-CGRP Medications?

Traditionally, approaches to migraine prevention have included medications for managing seizures, blood pressure, and antidepressants. Anti-CGRP treatments are the first preventive medications specifically developed for treating migraine.

Anti-CGRP treatments are also well tolerated, meaning they have very few adverse side effects. Reactions tend to be related to where the medication is injected since many of the anti-CGRP medications are given as a shot or infusion.

Some members of MyMigraineTeam claim that anti-CGRP medications work well for them. One member said, “CGRP worked for me immediately. I took it for 18 months, and during those 18 months I had six migraines that were less intense and short-lived.”

Another member said, “No other meds have helped other than CGRP.”

One member encouraged others, “Ask your doctor about one of the new CGRP drugs; they do work.”

What Is CGRP?

Calcitonin gene-related peptide is a protein present in everyone’s body that naturally helps protect the brain. CGRP is a vasodilator, meaning it helps the arteries dilate (widen) to increase blood flow, which is important for healing. CGRP influences the immune system by increasing levels of inflammation. For example, when the body has nerve damage, the body’s levels of CGRP increase. Researchers think that the increase in CGRP may be linked to the release of nerve growth factor, which is important for growing and maintaining nerve health.

CGRP works by activating receptors in the brain and cardiovascular systems. When the receptors are activated, the meninges (tissue surrounding the brain) becomes inflamed, contributing to migraine pain.

CGRP’s Role in Migraine

Over the past decade of research, scientists have found a link between elevated levels of CGRP and migraine. An area in the brain that processes sensory information, the posterior thalamic nuclei, becomes hyper or very sensitive during a migraine attack. Researchers have found evidence that CGRP increases the sensitivity of the posterior thalamic nuclei.

While health experts still don’t understand exactly how migraine attacks happen, they do know that if people prone to migraine attacks are given CGRP intravenously (into a vein), most of them will develop a migraine within four hours.

Overview of Anti-CGRP Drugs

There are two classes of anti-CGRP medications: CGRP receptor antagonists and CGRP monoclonal antibodies (mAbs).

Both types of anti-CGRP medications aim to disrupt the activity of CGRP to prevent migraine attacks. The nice thing about anti-CGRP medications is that they do not constrict blood vessels like conventional migraine medications (e.g., triptans). Rather, anti-CGRP medications prevent blood vessels from dilating.

CGRP Receptor Antagonists

The term “receptor antagonists” means these drugs prevent CGRP from binding to its normal receptors, which decreases its activity. Another term for CGRP receptor antagonists is “gepants.” Gepants bind to the CGRP receptors on the trigeminal ganglion (a group of neurons in the face and neck) and are more often used for acute treatment of migraine rather than prevention.

There are currently four gepants approved by the U.S. Food and Drug Administration (FDA):

• Ubrogepant (Ubrelvy) — An acute migraine treatment taken by tablet, typically given to people with migraine whose headache pain is not relieved by common over-the-counter drugs
• Atogepant (Qulipta) — A drug taken orally for preventive use rather than acute intervention
• Rimegepant (Nurtec ODT) — A drug taken by tablet as an acute or preventive migraine treatment
• Zavegepant (Zavzpret) — A nasal spray taken to treat acute migraine headaches after they’ve started

The most common side effects of gepants are fatigue, upset stomach, and dry mouth. It’s important to discuss symptoms with your doctor and to let them know about any other medications you’re taking in case there are interactions.

CGRP Monoclonal Antibodies

Monoclonal antibodies are a type of biologic therapeutic, meaning they are medicines derived from living cultures. Monoclonal antibodies (mAbs) remain active in a person’s body for several weeks, making the drug especially effective for inhibiting migraine attacks for a longer period of time.

As of 2024, the FDA has approved four CGRP monoclonal antibody medications for preventive migraine treatments. One of them, called erenumab-aooe (Aimovig), targets the CGRP receptor and is self-injected once per month. The other three target the CGRP protein itself:

• Eptinezumab-jjmr (Vyepti) — Administered intravenously once every three months
• Fremanezumab-vfrm (Ajovy) — Self-injected every one or three months
• Galcanezumab-gnlm (Emgality) — Self-injected once per month

CGRP mAb drugs need to be injected because they’re very large molecules. They do not cross the blood-brain barrier, nor are they broken down in the liver.

Is Anti-CGRP Therapy Right for You?

CGRP therapy may be especially beneficial for people who can’t tolerate other medications or for whom no other migraine treatments are working. However, more research needs to be done in some populations. Doctors don’t recommend CGRP drugs for people who are pregnant or who are already taking vasoconstrictive medication.

Unfortunately, the costs of CGRP medications are very high, which can be a significant barrier to newer treatments for people with migraine. One member of MyMigraineTeam commented, “I have been trying to get the new CGRP drugs. The problem is Medicare won’t cover them and my supplemental insurance only covers half.”

Another member said, “I might hold out for the CGRP injections. Should be available by June and hope insurance covers it.”

The National Headache Foundation offers a list of patient assistance programs (PAPs), which help people in need of financial assistance for purchasing necessary medications and devices. Drug companies, government agencies, and nonprofits can help provide those who qualify with free or lower-cost treatment.

Talk With Others Who Understand

MyMigraineTeam is the social network for people with migraine and their loved ones. On MyMigraineTeam, over 81,000 members come together to ask questions, give advice, and share their stories with others who understand life with migraine.

Are you living with chronic migraine and want to know more about anti-CGRP treatment? Have you tried anti-CGRP medication? Share your experience in the comments below, or start a conversation by posting on your Activities page.