Fremanezumab, sold under the brand name Ajovy, is a medication used to prevent

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

s in adults. It is given by injection under the skin. The most common side effect is pain and redness at the site of injection. Other side effects include allergic reactions. It is in the

calcitonin gene-related peptide antagonist Calcitonin gene-related peptide (CGRP) receptor antagonists are a class of drugs that act as antagonists of the calcitonin gene-related peptide receptor (CGRPR). Several monoclonal antibodies which binds to the CGRP receptor or peptide have been ap ...

class of medications. It was approved for medical use in the United States in 2018, the European Union in 2019 and the UK in 2020.

Medical uses

Fremanezumab was shown to be effective in adults with four or more attacks per month.

Adverse effects

The most common adverse effects are reactions at the injection site, which occurred in 43 to 45% of people in studies (as compared to 38% under placebo). Hypersensitivity reactions occurred in fewer than 1% of patients.

Interactions

Fremanezumab does not interact with other antimigraine drugs such as triptans, ergot alkaloids and analgesics. It is expected to generally have a low potential for interactions because it is not metabolized by

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzymes.

Pharmacology

Mechanism of action

Fremanezumab is a fully humanized monoclonal antibody directed against calcitonin gene-related peptides (CGRP) alpha and beta. The precise mechanism of action is unknown. It can be given with a quarterly interval.

Pharmacokinetics

After

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...

, fremanezumab has a bioavailability of 55–66%. Highest concentrations in the body are reached after five to seven days. Like other proteins, the substance is degraded by

proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

to small peptides and amino acids, which are reused or excreted via the kidney. The elimination half-life is estimated to be 30 to 31 days.

History

Fremanezumab was discovered and developed by Rinat Neuroscience, was acquired by Pfizer in 2006, and was then licensed to

Teva Teva is the Hebrew word for nature ( he, טבע, "nature"). Teva may refer to: Companies * Teva Footwear, American footwear manufacturer * Teva Naot, Israeli footwear manufacturer * Teva Pharmaceuticals, Israeli multinational pharmaceutical com ...

. It was approved by the US Food and Drug Administration in September 2018. In March 2019, fremanezumab was approved for marketing and use in the European Union. The drug has been and is still being evaluated for diseases other than migraine, where the endogenous substance CGRP has been implicated in the pathology. Teva is still developing it for episodic cluster headache but stopped development of fremanezumab for the treatment of chronic cluster headache in 2018 after the primary endpoint of a Phase III trial was not met.

Chemistry

Fremanezumab is a humanized monoclonal antibody. It is produced using recombinant DNA in Chinese hamster ovary cells.

References

External links

* {{Portal bar , Medicine Antimigraine drugs Monoclonal antibodies