Erenumab

Erenumab is a human monoclonal antibody that is used for migraine prophylaxis. The migraine antibody is directed against the calcitonin gene-related peptide (CGRP) receptor and is applied subcutaneously. Erenumab is the first representative of a new class of active substances.

The monoclonal antibody erenumab is used for the prophylaxis of episodic and chronic migraine in adults with at least four migraine days per month.

Erenumab is a human monoclonal IgG2 antibody that targets the calcitonin gene-related peptide (CGRP) receptor. By binding to this receptor, the interaction with the natural ligand CGRP is inhibited. CGRP is a neuropeptide that regulates nociceptive signal transmission and has a strong vasodilatory effect. This mechanism is associated with the pathophysiology of migraine. The CGRP level rises significantly during a migraine attack and falls when the symptoms subside.

Erenumab follows non-linear kinetics due to binding to the CGRP receptor. At therapeutically relevant doses, the pharmacokinetics of erenumab are predominantly linear after 4 weeks of subcutaneous administration, as binding to the CGRP receptor leads to saturation. After subcutaneous administration of 70 mg or 140 mg erenumab, maximum serum concentrations were reached after 4 to 6 days. The estimated absolute bioavailability is 82 %.

Erenumab has two elimination phases:

At low concentrations, elimination occurs primarily by binding to the CGRP receptor. At higher concentrations, elimination occurs predominantly via non-specific proteolytic degradation.

The recommended dose is 70 mg every 4 weeks as a single injection.

The following side effects were reported compared to placebo during treatment with 70 mg or 140 mg:

• Reactions at the injection site (5.6 % and 4.5 % respectively),
• constipation (1.3 % and 3.2 % respectively),
• muscle spasms (0.7 % and 2.0 % respectively) and
• pruritus (1.0 % and 1.8 % respectively).
• Most of these side effects were of mild or moderate severity.

Due to the metabolization pathways of monoclonal antibodies, no interactions with concomitantly administered drugs are expected.

It is not known whether erenumab passes into human breast milk. However, human IgGs pass into breast milk in the first few days after birth and their concentration drops to low levels soon afterwards. Accordingly, there could be a risk to the infant during this short phase.

Initial clinical results have been reported regarding efficacy in rosacea. The pathophysiology of rosacea is known to involve both the innate and adaptive immune systems, with signaling neuropeptides such as pituitary adenylate cyclase-activating polypeptide-38 and calcitonin gene-related peptide (CGRP) playing a role. Interestingly, there is a proven epidemiologic overlap between rosacea and migraine, suggesting a possible pathophysiologic link. Both diseases have been associated with elevated plasma CGRP levels (Wienholtz NKF et al. 2024).

Alternative preparations are antibodies that are not directed against the CGRP receptor but against CGRP itself:

• Galcanezumab
• Fremanezumab
• eptinezumab