Identification

Name
Reslizumab
Accession Number
DB06602
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Reslizumab is a humanized interleukin-5 (IL-5) antagonist monoclonal antibody (IgG4 kappa) that is produced by recombinant DNA technology in murine myeloma non-secreting 0 (NS0) cells. IL-5 is a pro-inflammatory cytokine that is responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils Label. Elevated levels of eosinophils increase the risk for asthma exacerbations, including both allergic forms and nonallergic forms of asthma where eosinophilia is prominent. By targeting the IL-5 and disrupting its signalling pathways, reslizumab aims to inhibit eosinophil maturation and promote programmed cell death 2.

Asthma is a chronic respiratory disease that causes inflammation in the lungs with asthma attacks that lead to severe breathing difficulties. Patients often experience persistent or exacerbating symptoms overtime despite conventional first-line therapies available. Inflammation-predominant asthma, which is chatacterized by eosinophilic infiltration of airway mucosa and elevated levels of eosinophils in the blood, sputum and BAL fluid, is associated with an increased risk for recurrent exacerbation and asthma-related hospitalizations 3. In four double-blind, randomized, placebo‑controlled trials in patients with severe asthma on currently available therapies, patients receiving reslizumab had fewer asthma attacks, and a longer time to the first attack compared to patients receiving placebo Label,3. In addition, a significant improvement in lung function was seen, as measured by the volume of air exhaled by patients in one second 4. Studies demonstrated that reslizumab was not effective in various asthma outcomes in patients without eosinophilia 1.

Reslizumab was developed by Teva Pharmaceuticals. Approved by the FDA in March 2016, reslizumab is marketed under the brand name Cinqair for intravenous injection. It is injected once every four weeks via intravenous infusion. Cinqair is indicated as an add-on maintenance therapy for adults with severe asthma with an eosinophilic phenotype. It is approved for patients who have a history of severe asthma attacks (exacerbations) despite receiving their current asthma medicines. Reslizumab is marketed as Cinqaero in Europe.

Protein structure
Db06602
Protein chemical formula
Not Available
Protein average weight
147000.0 Da (Approximate)
Sequences
Not Available
Synonyms
  • Reslizumab
External IDs
CEP-38072 / DCP 835 / DCP-835 / SCH-55700 / SCH55700
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CinqaeroInjection, solution, concentrate10 mg/mLIntravenousTeva2016-08-16Not applicableEu
CinqairSolution10 mgIntravenousTEVA Canada Limited2016-12-19Not applicableCanada
CinqairInjection, solution, concentrate10 mg/1mLIntravenousTeva Respiratory, LLC2016-04-18Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
35A26E427H
CAS number
241473-69-8

Pharmacology

Indication

Indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype.

Associated Conditions
Pharmacodynamics

A reduction in blood eosinophil counts was observed in clinical studies following an initial infusion of 3 mg/kg reslizumab and was maintained through 52 weeks of treatment with no signs of tachyphylaxis. Greater reductions of blood eosinophils were observed in subjects with higher reslizumab serum concentrations. This effect was independent of the presence of treatment-emergent anti-reslizumab antibodies Label.

Mechanism of action

Reslizumab an interleukin-5 (IL-5) antagonist (IgG4, kappa) that binds to IL-5 with a dissociation constant of 81 pM. IL-5 is a proinflammatory cytokine responsible for the terminal maturation of eosinophils and increases chemotaxis, endothelial adhesion, activation and survival of eosinophils. Eosinophils are known to play a central role in the pathophysiology of many patients with asthma; upon activation, eosinophils release leukotrienes, platelet activation factor, major basic protein, eosinophil cationic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and other cytokines that are cytotoxic to the bronchial epithelium and lead to airway inflammation and bronchospasm 1. IL-5 production is increased by upon activation of TH2 lymphocytes after antigen exposure and IL-5 stimulates the production and maturation of eosinophil precursors in the bone marrow 1. IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils via interacting with the IL-5 receptor expressed on the eosinophil surface Label. Increased production and activation of eosinophils is especially prominent in nonallergic forms of asthma 1.

Reslizumab is a humanized monoclonal antibody that occupies the region ERRR (glutamic acid, arginine, arginine, arginine) corresponding to amino acids 89–92 on IL-5, which is a region critical for its interaction with the IL-5 receptor on the eosinophil surface 1. By binding to IL-5 and disrupting its binding to the alpha chain of the IL-5 receptor complex, reslizumab inhibits the bioactivity of IL-5 and attenuates IL-5 signaling. Blocking of IL-5 signalling thereby reduces the production and survival of eosinophils and inhibits eosinophilic-driven inflammation.

TargetActionsOrganism
AInterleukin-5
antagonist
Humans
Additional Data Available
Adverse Effects

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Contraindications

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Blackbox Warnings

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Absorption

The peak serum concentrations of reslizumab were typically observed at the end of the infusion with the serum concentrations gradually declining from the peak in a biphasic manner. Following multiple doses, serum concentrations of reslizumab accumulated approximately 1.5 to 1.9-fold. Interindividual variability in peak and overall exposure across healthy individuals, patients with asthma, and other populations in pharmacokinetic studies was around 20-30% Label. Systemic exposure to reslizumab appeared to be unaffected by the presence of treatment-emergent anti-reslizumab antibodies.

Volume of distribution

The approximate volume of distribution of reslizumab is 5L, suggesting minimal distribution to the extravascular tissues Label.

Protein binding
Not Available
Metabolism

Like other monoclonal antibodies, reslizumab is assumed to undergo enzymatic proteolysis into smaller peptides and amino acids. As reslizumab bind to the target, it is not expected to undergo a target-mediated clearance Label.

Route of elimination
Not Available
Half life

The half-life is approximately 24 days Label.

Clearance

Reslizumab clearance was approximately 7 mL/hour Label.

Toxicity

Single doses of up to 732 mg have been administered intravenously to subjects in clinical trials without evidence of dose-related toxicities. There is no specific treatment for an overdose with reslizumab. If the event of an overdose, the patient should be treated supportively with appropriate monitoring as necessary Label.

Based on the findings of a 6-month bioassay, reslizumab showed no evidence of carcinogenicity. In a fertility study, administration of reslizumab to parental mice at doses up to 50 mg/kg (approximately 6 times the MRHD on an AUC basis) had no effects on male or female mating or fertility. The malignancy risk of reslizumab in humans with effects on tumor growth is not yet established Label.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Reslizumab.
AbituzumabThe risk or severity of adverse effects can be increased when Reslizumab is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Reslizumab is combined with Abrilumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Reslizumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Reslizumab.
AducanumabThe risk or severity of adverse effects can be increased when Reslizumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Reslizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Reslizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Reslizumab is combined with Alirocumab.
AmatuximabThe risk or severity of adverse effects can be increased when Reslizumab is combined with Amatuximab.
Additional Data Available
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    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
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Food Interactions
Not Available

References

General References
  1. Maselli DJ, Velez MI, Rogers L: Reslizumab in the management of poorly controlled asthma: the data so far. J Asthma Allergy. 2016 Aug 31;9:155-62. doi: 10.2147/JAA.S94164. eCollection 2016. [PubMed:27621657]
  2. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O'Brien C, Korn S: Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015 May;3(5):355-66. doi: 10.1016/S2213-2600(15)00042-9. Epub 2015 Feb 23. [PubMed:25736990]
  3. Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M: Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels: A Randomized Phase 3 Study. Chest. 2016 Oct;150(4):789-798. doi: 10.1016/j.chest.2016.03.032. Epub 2016 Apr 4. [PubMed:27056586]
  4. FDA approves Cinqair to treat severe asthma [Link]
External Links
PubChem Substance
347910352
RxNav
1746889
Wikipedia
Reslizumab
ATC Codes
R03DX08 — Reslizumab
AHFS Codes
  • 48:10.20 — Interleukin Antagonists
FDA label
Download (416 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAbsolute Bioavailability1
1RecruitingOtherHealthy Volunteers / Pharmacodynamics / Pharmacokinetics1
2CompletedTreatmentAsthma1
2CompletedTreatmentHypereosinophilic Syndromes1
2CompletedTreatmentLoiasis1
2CompletedTreatmentSevere Asthma1
2RecruitingTreatmentAsthma1
2, 3CompletedTreatmentOesophagitis, Eosinophilic1
2, 3Enrolling by InvitationTreatmentEosinophilic Bronchitis / Severe Persistent Asthma1
3CompletedTreatmentAsthma1
3CompletedTreatmentAsthma / Increased eosinophils / Oral Corticosteroid Dependence1
3CompletedTreatmentEosinophilic Asthma4
3CompletedTreatmentOesophagitis, Eosinophilic1
3RecruitingTreatmentSinusitis1
3TerminatedTreatmentEosinophilic Asthma1
3TerminatedTreatmentEosinophils, Asthma1
4TerminatedTreatmentAsthma1
Not AvailableRecruitingNot AvailableAsthma / Chronic Rhinosinusitis (Diagnosis) / Polyps, Nasal1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous10 mg/mL
Injection, solution, concentrateIntravenous10 mg/1mL
SolutionIntravenous10 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Interleukin-5 receptor binding
Specific Function
Factor that induces terminal differentiation of late-developing B-cells to immunoglobulin secreting cells.
Gene Name
IL5
Uniprot ID
P05113
Uniprot Name
Interleukin-5
Molecular Weight
15237.695 Da

Drug created on March 19, 2008 10:40 / Updated on May 28, 2020 00:58

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