CGRP Inhibitors

Products

Erenumab (Aimovig) was the first agent from the group of CGRP inhibitors to be approved in 2018. Fremanezumab (Ajovy) and galcanezumab (Emgality) followed.

Structure and properties

CGRP inhibitors are humanized or human monoclonal IgG antibodies directed against calcitonin gene-related peptide (CGRP). Low-molecular-weight CGRP receptor antagonists (so-called Gepante) are in clinical development. Some agents have demonstrated liver toxicity.

Effects

CGRP inhibitors reduce the number of migraine attacks. The effects are due to the binding of the antibodies to CGRP, the calcitonin gene-related peptide. CGRP is a neuropeptide that plays an important role in triggering migraine attacks. It consists of 37 amino acids and is expressed in the peripheral and central nervous systems. Two isoforms exist, CGRP-α (Figure) and CGRP-β, which differ in three amino acids. Both are agonists at the CGRP receptor. CGRP has potent vasodilatory properties and plays a central role in pain initiation as well as neurogenic inflammation. Migraineurs have been found to have elevated levels of CGRP during an attack, and intravenous administration of the peptide can induce attacks in migraineurs. Triptans, which are administered for the treatment of migraine attacks, also inhibit the release of CGRP.

Indications

  • For the prevention of attacks in chronic or episodic migraine.
  • For the prevention of cluster headache (galcanezumab).

Dosage

According to the professional information. The antibodies have a long half-life and therefore need to be injected subcutaneously only once a month or even once a quarter, for example. Eptinezumab is administered intravenously. The long dosing interval is an advantage for treatment adherence.

Agents

  • Erenumab (Aimovig) does not bind to CGRP but to the CGRP receptor. It is therefore referred to as a CGRPR inhibitor.
  • Fremanezumab (Ajovy).
  • Galcanezumab (Emgality)

Still without approval:

  • Eptinezumab (ALD403)

Contraindications

Full precautions can be found in the drug label.

Interactions

The risk for drug-drug interactions is much lower with antibodies than with traditional migraine medications and pain relievers.

Adverse effects

The most common potential adverse effects include injection site reactions such as pain, itching, and redness. Effective migraine prophylaxis can prevent adverse effects from pain relievers and migraine medications, which are often overused by migraine sufferers. Unlike CGRP receptor antagonists, the antibodies are not hepatotoxic.