Mepolizumab

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Mepolizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetIL-5
Names
Trade namesNucala
Clinical data
Main usesEosinophilic asthma, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome[1]
Side effectsHeadache, injection site reactions, back pain[2]
Pregnancy
category
  • AU: B1[3]
  • US: N (Not classified yet)[3]
Routes of
use		Subcutaneous injection
Typical dose100 mg q 4 wks[2]
External links
AHFS/Drugs.comMonograph
MedlinePlusa615058
Legal
License data
Legal status
Pharmacokinetics
Bioavailability80% (estimate)
Protein bindingNone
MetabolismProteolytic enzymes
Elimination half-life20 (16–22) days
Chemical and physical data
Molar mass149 000

Mepolizumab, sold under the brand name Nucala, is medication used to treat eosinophilic asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic 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 include anaphylaxis, shingles, and urinary tract infection.[1] It should not be given to people with helminth infections.[4] It is a monoclonal antibody which binds to and blocks interleukin-5 (IL-5) which decreases eosinophils.[1]

Mepolizumab was approved for medical use in the United States and Europe in 2015.[1][2] In the United Kingdom it costs about the NHS 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 to placebo (9.5% to 5.6%).[9]

It is also used to treat adults with eosinophilic granulomatosis with polyangiitis, which is a rare autoimmune condition that can cause vasculitis.[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 the urinary tract (3% versus 2%) and the lower 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 to its receptor, more specifically the interleukin 5 receptor alpha subunit, on the surface of eosinophil white blood cells. While eosinophils play a role in inflammation associated with asthma, the exact mechanism of mepolizumab is unknown.[13]

Pharmacokinetics

After subcutaneous injection, mepolizumab has an estimated bioavailability 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 is 20 days on average, ranging from 16 to 22 days in different individuals.[12][13]

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, 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] The European 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 of atopic dermatitis, hypereosinophilic syndrome (HES), eosinophilic esophagitis (EoE),[16] nasal polyposis, eosinophilic granulomatosis with polyangiitis, and chronic obstructive pulmonary disease.

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Mepolizumab Monograph for Professionals". Drugs.com. Archived from the original on 4 March 2021. Retrieved 16 November 2021.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Nucala EPAR". European Medicines Agency (EMA). Archived from the original on 12 October 2020. Retrieved 8 October 2020.
  3. ↑ 3.0 3.1 "Mepolizumab (Nucala) Use During Pregnancy". Drugs.com. 14 June 2019. Archived from the original on 5 December 2020. Retrieved 8 October 2020.
  4. ↑ 4.0 4.1 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 284. ISBN 978-0857114105.
  5. ↑ "Nucala Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 26 February 2021. Retrieved 16 November 2021.
  6. ↑ "FDA approves severe eosinophilic asthma treatment for children ages 6-11". AAP News. 2020-01-30. Archived from the original on 2020-02-01. Retrieved 2021-07-30.
  7. ↑ Bermejo, I; Stevenson, M; Cooper, K; Harnan, S; Hamilton, J; Clowes, M; Carroll, C; Harrison, T; Saha, S (February 2018). "Mepolizumab for Treating Severe Eosinophilic Asthma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal". Pharmacoeconomics. 36 (2): 131–144. doi:10.1007/s40273-017-0571-8. PMID 28933002. S2CID 46768449. Archived from the original on 10 July 2021. Retrieved 1 July 2021.
  8. ↑ 8.0 8.1 "Nucala EPAR Summary for the public" (PDF). European Medicines Agency. December 2015. Archived (PDF) from the original on 2018-03-17. Retrieved 2021-07-30.
  9. ↑ Yancey SW, Ortega HG, Keene ON, Mayer B, Gunsoy NB, Brightling CE, et al. (April 2017). "Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma". The Journal of Allergy and Clinical Immunology. 139 (4): 1167–1175.e2. doi:10.1016/j.jaci.2016.08.008. PMID 27726946. Archived from the original on 2021-10-30. Retrieved 2021-07-30.
  10. ↑ "FDA approves first drug for Eosinophilic Granulomatosis with Polyangiitis, a rare disease formerly known as the Churg-Strauss Syndrome". U.S. Food and Drug Administration (FDA) (Press release). Archived from the original on 2018-01-25. Retrieved 2017-12-13.
  11. ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 "FDA Approves First Drug to Treat Group of Rare Blood Disorders in Nearly 14 Years". U.S. Food and Drug Administration (FDA) (Press release). 25 September 2020. Archived from the original on 29 September 2020. Retrieved 8 October 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  12. ↑ 12.0 12.1 12.2 12.3 "Nucala Summary of Product Characteristics" (PDF). European Medicines Agency. December 2015. Archived (PDF) from the original on 2018-03-17. Retrieved 2021-07-30.
  13. ↑ 13.0 13.1 13.2 13.3 FDA Professional Drug Information for Nucala.
  14. ↑ "Nucala European Public Assessment Report" (PDF). European Medicines Agency. 24 September 2015. p. 10. Archived (PDF) from the original on 17 March 2018. Retrieved 30 July 2021.
  15. ↑ "FDA approves Nucala to treat severe asthma" (Press release). U.S. Food and Drug Administration (FDA). 4 November 2016. Archived from the original on 25 January 2018. Retrieved 30 July 2021.
  16. ↑ "Intravenous Mepolizumab in Children with Eosinophilic Esophagitis". U.S. National Library of Medicine. 3 September 2018. Archived from the original on 9 August 2020. Retrieved 30 July 2021. {{cite journal}}: Cite journal requires |journal= (help)

External links

External sites:
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