Fremanezumab, sold under the brand name Ajovy, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used to prevent

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

s in adults. It is given by

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 (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...

(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 class of medications. It was approved for medical use in the United States in 2018, the European Union in 2019, the United Kingdom in 2020, and Argentina by September 2021.

Medical uses

Fremanezumab was shown to be effective in adults with four or more attacks per month. It comes in Monthly and Quarterly injection dosages.

Adverse effects

The most common adverse reactions are located at the injection site, which occurred in 43 to 45% of people in studies (as compared to 38% under

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

Hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...

reactions occurred in fewer than 1% of patients.

Interactions

Fremanezumab does not interact with other antimigraine drugs such as

triptan Triptans are a family of tryptamine-based medication, drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual h ...

ergot alkaloid Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous for ...

s and

analgesics An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

. It is expected to generally have a low potential for interactions, because it is not metabolized by

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzymes.

Pharmacology

Mechanism of action

Fremanezumab is a fully humanized

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

directed against

calcitonin gene-related peptide Calcitonin gene-related peptide (CGRP) is a neuropeptide that belongs to the calcitonin family. Human CGRP consists of two Protein isoform, isoforms, CGRP alpha (α-CGRP, also known as CGRP I) and CGRP beta (β-CGRP, also known as CGRP II). α-C ...

s (CGRP) alpha and beta. It potently and selectively binds to CGRPs, which prevents binding to receptors.

Pharmacokinetics

After

, fremanezumab has a

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

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. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...

to small

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

s and

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s, which are reused or excreted via the kidney. The

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

is estimated to be 31 days.

Chemistry

Fremanezumab is a humanized monoclonal antibody. It is produced using

recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...

Chinese hamster ovary cell Chinese hamster ovary (CHO) cells are a family of immortalized cell lines derived from epithelial cells of the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therap ...

History

Fremanezumab was discovered and developed by Rinat Neuroscience, was acquired by

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

in 2006, and was then licensed to Teva. It was approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

in September 2018. In March 2019, fremanezumab was approved for marketing and use in the European Union.

References

{{Portal bar , Medicine Antimigraine drugs Monoclonal antibodies