Mepolizumab, sold under the brand name Nucala by

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

, is a 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 ...

used for the treatment of severe eosinophilic asthma,

eosinophilic granulomatosis with polyangiitis Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as allergic granulomatosis, is an extremely rare autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of ...

, and

hypereosinophilic syndrome Hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous sys ...

(HES). It recognizes and blocks

interleukin-5 Interleukin 5 (IL-5) is an interleukin produced by type-2 T helper cells and mast cells. Function Through binding to the interleukin-5 receptor, interleukin 5 stimulates B cell growth and increases immunoglobulin secretion—primarily Ig ...

(IL-5), a signalling protein of the immune system. The most common side effects include headache, injection site reactions, and back pain.

Medical uses

Mepolizumab is approved by the U.S.

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 ...

(FDA) for the maintenance treatment of severe asthma in patients aged six years or older and with an eosinophilic phenotype in combination with other medicines used to treat asthma. In the European Union it is approved as an add-on treatment for severe refractory eosinophilic asthma in adults. In studies, mepolizumab cut the necessity for hospitalisation due to asthma

exacerbation In medicine, an exacerbation is the worsening of a disease or an increase in its symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person' ...

s in half, as compared to

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 ...

. In December 2017, the FDA expanded mepolizumab's indication to treat adults with

, which is a rare autoimmune condition that can cause

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both artery, arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily c ...

. In September 2020, the FDA expanded mepolizumab's indication to treat adults and children aged twelve years and older with hypereosinophilic syndrome (HES) for six months or longer without another identifiable non-blood related cause of the disease. In May 2025, the FDA approved mepolizumab as an add-on therapy for patients with chronic obstructive pulmonary disease (COPD) who exhibit an eosinophilic phenotype.

Side effects

Common side effects in clinical trials included headache (19% of patients under mepolizumab treatment versus 18% under placebo),

injection site reaction Injection site reactions (ISRs) are reactions that occur at the site of injection of a drug. They may be mild or severe and may or may not require medical intervention. Some reactions may appear immediately after injection, and some may be delayed ...

s (8% versus 3%), infections of the

urinary tract The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressu ...

(3% versus 2%) and the

lower respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of conducting air to the alveoli for the purposes of gas exchange in mammals. The respiratory tract is lined with respiratory epithelium as respirator ...

eczema Dermatitis is a term used for different types of skin inflammation, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened ...

and muscle spasms (both 3% versus <1%). for Nucala. The most common side effects in people with hypereosinophilic syndrome (HES) include: upper respiratory tract infection and pain in extremities (such as the hands, legs and feet).

Overdose

Single doses of 15 times the usual therapeutic dose have been tolerated in studies without significant side effects.

Interactions

No interaction studies have been conducted. As with other monoclonal antibodies, the interaction potential is considered to be low.

Pharmacology

Mechanism of action

Mepolizumab binds to IL-5 and prevents it from binding to its receptor, more specifically the interleukin 5 receptor alpha subunit, on the surface of

eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...

white blood cells. While eosinophils play a role in inflammation associated with asthma, the exact mechanism of mepolizumab is unknown.

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

, mepolizumab has an estimated

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 80% and reaches highest blood plasma concentrations after four to eight days. Like other antibodies, it is degraded by

proteolytic enzyme A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do t ...

s. Its

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

is 20 days on average, ranging from 16 to 22 days in different individuals.

Chemistry

The substance is an IgG₁ kappa monoclonal antibody, the two heavy chains consisting of 449

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 each, and the two light chains consisting of 220 amino acids each. The protein part has a

molar mass In chemistry, the molar mass () (sometimes called molecular weight or formula weight, but see related quantities for usage) of a chemical substance ( element or compound) is defined as the ratio between the mass () and the amount of substance ...

of about 146

kDa The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

, and the sugar part of 3 kDa.

History

Phase III clinical trials in severe eosinophilic asthma were completed in 2014. The FDA approved it in November 2015. The

European Commission The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...

granted a marketing authorization valid throughout the European Union on 2 December 2015. Mepolizumab was approved for medical use in the European Union in December 2015. In September 2020, mepolizumab was approved in the United States to treat adults and children aged twelve years and older with hypereosinophilic syndrome (HES) for six months or longer without another identifiable non-blood related cause of the disease. In January 2024, mepolizumab was approved in China for use in severe asthma with an eosinophilic phenotype. Mepolizumab was evaluated in a randomized, double-blind, multicenter, placebo-controlled trial in 108 participants with hypereosinophilic syndrome (HES). In the study, participants were randomly assigned to receive mepolizumab or placebo by injection every four weeks. The trial compared the proportion of subjects who experienced a HES flare during the 32-week treatment period. A HES flare was defined as worsening of clinical signs and symptoms of HES or increasing eosinophils (disease-fighting white blood cells) on at least two occasions. The trial compared the proportions of participants with at least one flare over a 32-week treatment period, as well as the time to the first flare. Fewer participants in the mepolizumab treatment group (28%) had HES flares compared to participants in the placebo group (56%), with a 50% relative reduction. In addition, the time to the first HES flare was later, on average, for participants treated with mepolizumab versus placebo. In May 2025, the FDA approved mepolizumab as an add-on therapy for patients with chronic obstructive pulmonary disease (COPD) who exhibit an eosinophilic phenotype.

Research

Mepolizumab has been investigated or is under investigation for the treatment of

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin. Atopic dermatitis is also often called simply eczema but the same term is also used to refer to dermatitis, the larger group of skin conditi ...

(HES),

eosinophilic esophagitis Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus that involves eosinophils, a type of white blood cell. In healthy individuals, the esophagus is typically devoid of eosinophils. In EoE, eosinophils migrate t ...

(EoE),

nasal polyposis Nasal is an adjective referring to the nose, part of human or animal anatomy. It may also be shorthand for the following uses in combination: * With reference to the human nose: ** Nasal administration, a method of pharmaceutical drug delivery ** ...

, and

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...

References

{{Portal bar , Medicine Antiasthmatic drugs Drugs developed by GSK plc Immunosuppressants Anti-interleukin monoclonal antibodies Orphan drugs