Mepolizumab, sold under the brand nameNucala, is medication used to treateosinophilic asthma,eosinophilic granulomatosis with polyangiitis, andhypereosinophilic syndrome.^[1] It is given by injection under the skin.^[1] Effects begin in about three days and can last up to 6 months.^[1]

Common side effects include headache, injection site reactions, and back pain.^[2] Other side effects may includeanaphylaxis,shingles, andurinary tract infection.^[1] It should not be given to people withhelminth infections.^[4] It is amonoclonal antibody which binds to and blocksinterleukin-5 (IL-5) which decreaseseosinophils.^[1]

Mepolizumab was approved for medical use in the United States and Europe in 2015.^[1][2] In the United Kingdom it costs about theNHS about £840 per dose.^[4] In the United States this amount costs about 3,300 USD.^[5]

Medical uses

Mepolizumab is used for the maintenance treatment of severe asthma in people aged six years^[6] or older and with an eosinophilic phenotype in combination with other medicines.^[7] In Europe it is approved as an add-on treatment for severe refractory eosinophilic asthma in adults.^[8][2]

It decreases the need for for hospitalisation due to asthma by nearly half, as compared toplacebo (9.5% to 5.6%).^[9]

It is also used to treat adults witheosinophilic granulomatosis with polyangiitis, which is a rare autoimmune condition that can causevasculitis.^[10] And 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.^[11]

Dosage

It is given at a dose of 100 mg in people aged 12 years and above, and 40 mg in people aged 6 to 11 years.^[2] Doses are given every 4 weeks.^[2]

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 theurinary tract (3% versus 2%) and thelower respiratory tract,eczema and muscle spasms (both 3% versus <1%).^[12][13]

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).^[11]

Overdose

Single doses of 15 times the usual therapeutic dose have been tolerated in studies without significant side effects.^[12][13]

Interactions

No interaction studies have been conducted. As with other monoclonal antibodies, the interaction potential is considered to be low.^[12]

Pharmacology

Mechanism of action

Mepolizumab binds to IL-5 and prevents it from binding toits receptor, more specifically theinterleukin 5 receptor alpha subunit, on the surface ofeosinophil white blood cells. While eosinophils play a role in inflammation associated with asthma, the exact mechanism of mepolizumab is unknown.^[13]

Pharmacokinetics

Aftersubcutaneous injection, mepolizumab has an estimatedbioavailability of 80% and reaches highest blood plasma concentrations after four to eight days. Like other antibodies, it is degraded byproteolytic enzymes. Itsbiological half-life is 20 days on average, ranging from 16 to 22 days in different individuals.^[12][13]

Chemistry

The substance is anIgG₁ kappa monoclonal antibody, the twoheavy chains consisting of 449 amino acids each, and the twolight chains consisting of 220 amino acids each. The protein part has a molar mass of about 146kDa, and the sugar part of 3 kDa.^[14]

History

Phase III clinical trials in severe eosinophilic asthma were completed in 2014. The FDA approved it in November 2015.^[15] TheEuropean Commission granted a marketing authorization valid throughout the European Union on 2 December 2015.^[8]

Mepolizumab was approved for medical use in the European Union in December 2015.^[11]

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.^[11]

Mepolizumab was evaluated in a randomized, double-blind, multicenter, placebo-controlled trial in 108 participants with hypereosinophilic syndrome (HES).^[11] In the study, participants were randomly assigned to receive mepolizumab or placebo by injection every four weeks.^[11] The trial compared the proportion of subjects who experienced a HES flare during the 32-week treatment period.^[11] 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.^[11] 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.^[11] Fewer participants in the mepolizumab treatment group (28%) had HES flares compared to participants in the placebo group (56%), with a 50% relative reduction.^[11] In addition, the time to the first HES flare was later, on average, for participants treated with mepolizumab versus placebo.^[11]

Research

Mepolizumab has been investigated or is under investigation for the treatment ofatopic dermatitis,hypereosinophilic syndrome (HES),eosinophilic esophagitis (EoE),^[16]nasal polyposis,eosinophilic granulomatosis with polyangiitis, andchronic obstructive pulmonary disease.

References

External links

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