Mepolizumab, sold under the brand name Nucala, 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 antibodies ...
used for the treatment of severe
eosinophilic asthma, eosinophilic granulomatosis, and hypereosinophilic syndrome (HES).
It recognizes and blocks
interleukin-5 (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 federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(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
exacerbations in half, as compared to
placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
.
In December 2017, the FDA expanded mepolizumab's indication to treat adults with
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 ...
, which is a rare autoimmune condition that can cause
vasculitis
Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...
.
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.
[ ]
Side effects
Common side effects in clinical trials included headache (19% of patients under mepolizumab treatment versus 18% under placebo), reactions at the site of injection (8% versus 3%), infections of the
urinary tract
The 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 pressure, c ...
(3% versus 2%) and the
lower respiratory tract,
eczema
Dermatitis is inflammation of the skin, 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. The area of skin involved c ...
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 (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
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 into the subcutis, the layer of skin directly below the dermis and epidermis, c ...
, 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%. Ho ...
of 80% and reaches highest blood plasma concentrations after four to eight days. Like other antibodies, it is degraded by
proteolytic enzymes. Its
biological half-life
Biological half-life (also known as elimination half-life, pharmacologic 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 bl ...
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 acids each, and the two
light chains consisting of 220 amino acids each. The protein part has a molar mass of about 146
kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
, 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 executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body ...
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.
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.
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 ( dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens over tim ...
,
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),
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 ...
(EoE),
nasal polyposis,
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
chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
.
References
External links
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