Fremanezumab Overview

Introduction of Fremanezumab

Fremanezumab is a humanized monoclonal antibody directed against calcitonin gene-related peptides (CDRPs) alpha and beta. It was originated by Rinat Neurosciences, which licensed it to Teva. In 2018 Teva stopped development of fremanezumab for the treatment of chronic cluster headache after the primary endpoint of a Phase III trial was not met; Teva was still developing it for episodic cluster headache and migraine.

Mechanism of Action of Fremanezumab

Migraine headache is associated with activation of trigeminal durovascular nociceptive afferents and release of CGRP. Fremanezumab binds to both α and β isoforms of CGRP and inhibits the interaction between CGRP and its’ receptor, thereby shows efficacy in the treatment of migraine. Indeed, CGRP release has been demonstrated in both triggered and spontaneous migraine attacks, and CGRP levels are reduced by effective treatment with a triptan. Given the short half-life of CGRP (under 10 min) and dilution in the periphery, the observed release of CGRP in the external jugular vein during attacks was not associated with an increase in cubital fossa vein CGRP level. Intravenous infusion of CGRP triggers delayed migraine attacks, at least in a subgroup of migraine patients, indicating CGRP release is not an epiphenomenon of a migraine attack. Migraine is much more prevalent in women than men; this sex difference may be due to fluctuations of ovarian steroid hormones (mainly estrogen) that modulate CGRP in the trigeminovascular system during different reproductive milestones. CGRP is a 37-amino acid neuropeptide that exists in two isoforms that differ by three amino acids in the human and have different tissue distributions. In the peripheral nervous system, α-CGRP is predominantly expressed in the nociceptive Ad and C fibers, with widespread innervation throughout the body, including an extensive perivascular distribution; β-CGRP is the predominant form expressed in the enteric nervous system. The distribution of CGRP and the CGRP receptor in the central nervous system is exquisitely complex and still largely enigmatic. CGRP is also expressed in nonneuronal tissues of which less is known. CGRP belongs to a family of peptides that also includes calcitonin, amylin, adrenomedullin and adrenomedullin 2/intermedin. Amylin was discovered in the b cells of the pancreas and is cosecreted with insulin. Pramlintide, an analog of amylin, is US Food and Drug Administration (FDA) approved for type 1 and type 2 diabetic patients who use insulin. CGRP exerts its action on the CGRP receptor, also called the canonical CGRP receptor. The CGRP receptor is a heterodimer of calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1). In addition, the receptor component protein needs to be present to form a functional CGRP receptor. CGRP also has a high potency at the amylin 1 receptor, a heterodimer of CLR and RAMP2, and may activate it physiologically. The potential overlapping biological action of amylin and CGRP, including in the trigeminovascular system, thus requires clarification. Established biological roles for CGRP are vasodilator activity and (modulation of) nociception. CGRP is the most potent microvascular dilator currently known, and its vasodilator activity is observed in the cerebral, coronary and kidney vascular beds. There are data to support the notion that CGRP may act as a vasodilatory safeguard during cerebral and cardiac ischemia. Additional roles of CGRP in biology and pathophysiology have been discussed, including in hypertension, wound healing and diabetes.

Fig.1 Mechanism of action of fremanezumab

Clinical Projects of Fremanezumab*

What We Provide

Therapeutic Antibody

Fremanezumab

We provide high-quality Fremanezumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Fremanezumab

For research use only. Not intended for any clinical use.