What are CGRPs?

CGRP stands for calcitonin-gene-related peptide. It is a newly identified protein that acts like a neurotransmitter (a chemical messenger) throughout the brain and body. CGRP is present in large numbers in the trigeminal system, the sensory nerves that supply the head and neck. Researchers discovered CGRP is found in high levels in migraine sufferers during an attack, providing a new target for pharmaceutical drugs to focus on. To target CGRP, pharmaceutical researchers have developed monoclonal antibodies, a type of biologic therapy that targets and neutralizes either CGRP or its receptors. These new treatments are actually CGRP antagonists or CGRP blocker medications, as they selectively block one of the receptors CGRP attaches to, but they are commonly referred to as CGRP medications.1,2

Three CGRP blockers – Aimovig™ (erenumab-aooe), developed by Novartis and Amgen3, Ajovy (fremanezumab-vfrm), developed by Teva, and Emgality (galcanezumab-gnlm), developed by Eli Lilly – have been approved by the U.S. Food and Drug Administration (FDA), and several others are currently in development. One has been submitted to the U.S. Food and Drug Administration (FDA) for possible approval, and one more is still in phase III clinical trials. Phase III clinical trials study a particular treatment in large numbers of patients to determine the effectiveness of a drug, as well as understand any potential side effects, and are required before filing for approval from the (FDA). The two anti-CGRP products currently in development are:

  • Eptinezumab (ALD403), developed by Alder Biopharmaceuticals1
  • Ubrogepant, developed by Allergan (still in phase III clinical trials)4

How effective are CGRP blockers?

In addition to the novelty of a new treatment option, CGRP blockers have shown promising results in their ability to reduce the number of migraine days per month or reduce the pain associated with migraines. Four of the CGRP blockers – erenumab, galcanezumab, fremanezumab, and eptinezumab – are preventive migraine medications, given to reduce the frequency and severity of episodic and chronic migraines. Ubrogepant is an acute migraine medication, given when a migraine attack occurs to stop the migraine and provide relief from migraine symptoms.

It is important to note that the results from each of the clinical trials cannot be compared to each other, as each trial was set up differently. There have been no head-to-head studies comparing the CGRP blockers to each other. Some of the findings from clinical trials include:

  • Erenumab demonstrated a reduction of 6.6 fewer migraine days per month5
  • Galcanezumab demonstrated at least a 50% reduction in migraine headache days compared to placebo6
  • Fremanezumab demonstrated a reduction of 3.4 to 3.7 fewer migraine days per month7
  • Eptinezumab demonstrated a reduction of 3.9 to 4.3 fewer migraine days per month8
  • Of patients taking ubrogepant for a migraine attack, 20.7% to 21.8% experienced freedom from pain two hours after their first dose3

How are CGRP blockers administered?

The different CGRP blockers are administered in various ways:

  • Erenumab and galcanezumab are given by subcutaneous (under the skin) injection monthly
  • Fremanezumab is given by subcutaneous injection monthly or once every three months
  • Eptinezumab is administered by intravenous (IV) infusion every 12 weeks
  • Ubrogepant is an oral tablet given as an acute medication to treat a migraine attack

What are common side effects of CGRP blockers?

Each CGRP blocker will have its own unique safety profile, but early results from clinical trials have indicated that these new medications will be more tolerable than other medications currently available for migraine.

Common side effects of CGRP blockers include:

  • Injection site pain (for those that are injected)
  • Upper respiratory tract infection
  • Runny/stuffy nose
  • Back, abdominal, or joint pain
  • Urinary tract infection
  • Fatigue
  • Nausea and vomiting7,9-11
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