Reslizumab

Reslizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from rat)
TargetIL-5
Names
Trade namesCinqair, Cinqaero, others
Clinical data
Drug classMonoclonal antibody[1]
Main usesEosinophilic asthma[2]
Side effectsAllergic rhinitis, shortness of breath, muscle damage, anaphylaxis[3][1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Routes of
use		Intravenous
Typical dose3 mg/kg[2]
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Pharmacokinetics
MetabolismProteolysis
Elimination half-life~24 days

Reslizumab, sold under the brand name Cinqair among others, is a medication used for eosinophilic asthma uncontrolled by other measures.[2][4] It is used by injection into a vein.[2] Use is not recommended in Scotland due to a lack of cost benefit.[4]

Common side effects include allergic rhinitis, shortness of breath, and muscle damage.[3][1] Other side effects may include cancer and anaphylaxis.[3] It is a monoclonal antibody that attaches to and blocks interleukin-5 (IL-5).[1]

Reslizumab was approved for medical use in the United States and Europe in 2016.[2][1] In the United States a 100 mg vial costs about 1,050 USD as of 2021.[5] This amount in the United Kingdom costs the NHS about £500.[4]

Medical uses

Eosinophilic asthma

Reslizumab was first used for eosinophilic asthma in 2008. In a 106-patient, phase II clinical trial, the researchers showed reslizumab was effective in reducing sputum eosinophils. Furthermore, the patients receiving reslizumab showed improvements in airway function, and a general trend toward greater asthma control than those receiving placebo was observed.[6] A showed that reslizumab was effective at improving lung function, asthma control, and quality of life in comparison to placebo. These results led to the FDA approval for the maintenance treatment of severe asthma in patients aged 18 years and older, with an eosinophilic phenotype on March 23, 2016.[7]

The benefits with reslizumab are its ability to reduce the exacerbation rate and improve lung function and asthma-related quality of life in patients with severe eosinophilic asthma (with blood eosinophil count ≥ 400 cells/μL) and with at least one previous asthma exacerbation in the preceding year.

Dosage

It is given at a dose of 3 mg/kg every 4 weeks.[2]

Side effects

Common side effects include:

Less common adverse effects include:

  • musculoskeletal pain
  • neck pain
  • muscle spasms
  • extremity pain
  • muscle fatigue
  • anaphylaxis
  • malignancy

The most common side effect of reslizumab was oropharyngeal (mouth and throat) pain. According to the phase III clinical trials data, oropharyngeal pain occurred in ≥2% of individuals along with elevated baseline creatine phosphokinase (CPK), which was more common in patients treated with reslizumab versus placebo. Myalgia was also reported more in patients in the reslizumab 3 mg/kg group versus the placebo group as well as some musculoskeletal adverse reactions. Lastly, some serious adverse reactions that occurred in subjects treated with reslizumab but not in those treated with placebo included anaphylaxis and malignancy.[8]

Pharmacology

Mechanism of action

Reslizumab is an interleukin-5 antagonist monoclonal antibody. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Eosinophils play a role in the mediation of inflammation in the airways. Eosinophilic asthma is a phenotype of asthma that is characterized by the higher than normal presence of eosinophils in the lung and sputum. It has been shown that the numbers of eosinophils in the blood and bronchial fluid can correlate with asthma severity.[9] Reslizumab binds to IL-5 with a dissociation constant of 81 pM and inhibiting IL-5 signaling, which reduces the production and survival of eosinophils. However, the mechanism of reslizumab action in asthma has not been definitively established.[7]

Pharmacodynamics

Reductions in blood eosinophil counts were observed following the first dose of reslizumab and maintained through 52 weeks of treatment. In phase III clinical trials, mean eosinophil counts were 696 cells/µL (n=245) and 624 cells/µL (n=244) at baseline. Following 52 weeks of reslizumab treatment, eosinophil cells were counted and were reported to be 55 cells/µL (92% reduction, n=212) and 496 cells/µL (21% reduction, n=212) for the reslizumab and placebo treatment groups, respectively. Furthermore, eosinophil count returned towards baseline in those reslizumab-treated patients who completed a follow-up assessment (n=35, 480 cells/µL), approximately 120 days after the last dose of reslizumab. Therefore, reductions of blood eosinophils were related to reslizumab serum levels.[10]

Pharmacokinetics

The pharmacokinetic characteristics of reslizumab are similar across the children and adults. Peak serum concentrations are observed at the end of infusion and declines in a biphasic manner. The mean observed accumulation ratio of reslizumab following multiple doses of administration ranged from 1.5 to 1.9-fold. Reslizumab has a volume of distribution of approximately 5 L, clearance of approximately 7 mL/hour, and a half-life of about 24 days. Reslizumab is degraded by enzymatic proteolysis into small peptides and amino acids, as are other monoclonal antibodies.[11]

Chemistry

Reslizumab is supplied as a refrigerated, sterile, single-use, preservative-free solution for intravenous infusion. The reslizumab solution is a slightly hazy/opalescent, slightly yellow liquid and is supplied as 100 mg in a 10 mL glass vial. Each single-use vial of reslizumab is formulated as 10 mg/mL reslizumab in an aqueous solution containing 2.45 mg/mL sodium acetate trihydrate, 0.12 mg/mL glacial acetic acid, and 70 mg/mL sucrose, with a pH of 5.5.[12]

History

Reslizumab was initially developed by Chuan-Chu Chou at Schering-Plough and was previously known as SCH-55700. In 1993, Chou and his group at Schering-Plough were granted the patent for the design, cloning and expression of the reslizumab drug.[13] Ception Therapeutics acquired the drug and continued its development under the name CTx55700. In 2010, Ception Therapeutics was acquired by Cephalon for $250 million and the drug continued under development under the codename CEP-38072.[14] In 2011, Teva Pharmaceuticals acquired Cephalon for $6.8 billion and continued the development of reslizumab.[15]

References

  1. 1 2 3 4 5 "Cinqaero". Archived from the original on 4 March 2021. Retrieved 16 October 2021.
  2. 1 2 3 4 5 6 "DailyMed - CINQAIR- reslizumab injection, solution, concentrate". dailymed.nlm.nih.gov. Archived from the original on 25 March 2021. Retrieved 16 October 2021.
  3. 1 2 3 "Reslizumab Monograph for Professionals". Drugs.com. Archived from the original on 4 March 2021. Retrieved 16 October 2021.
  4. 1 2 3 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 284. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
  5. ↑ "Cinqair Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 29 September 2020. Retrieved 16 October 2021.
  6. ↑ Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, et al. (November 2011). "Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study". American Journal of Respiratory and Critical Care Medicine. 184 (10): 1125–32. doi:10.1164/rccm.201103-0396OC. PMID 21852542.
  7. 1 2 "CENTER FOR DRUG EVALUATION AND RESEARCH : APPLICATION NUMBER : 761033Orig1s000" (PDF). Accessdata.fda.gov. Archived (PDF) from the original on 2016-11-11. Retrieved 2016-11-22.
  8. ↑ "CENTER FOR DRUG EVALUATION AND RESEARCH : APPLICATION NUMBER : 761033Orig1s000" (PDF). Accessdata.fda.gov. Archived from the original on 2021-08-29. Retrieved 2016-11-22.
  9. ↑ Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, et al.. Eosinophilic inflammation in asthma. N Engl J Med 1990;323:1033–1039.DOI: 10.1056/NEJM199010113231505
  10. ↑ "HIGHLIGHTS OF PRESCRIBING INFORMATION : CINQAIR" (PDF). Accessdata.fda.gov. Archived (PDF) from the original on 2016-12-13. Retrieved 2016-11-22.
  11. ↑ Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O'Brien C, Korn S (May 2015). "Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials". The Lancet. Respiratory Medicine. 3 (5): 355–66. doi:10.1016/S2213-2600(15)00042-9. PMID 25736990.
  12. ↑ "PULMONARY-ALLERGY DRUGS ADVISORY COMMITTEE (PADAC) MEETING" (PDF). Fda.gov. Archived (PDF) from the original on 2016-10-24. Retrieved 2016-11-22.
  13. ↑ WO 1993016184, "Design, cloning and expression of humanized monoclonal antibodies against human interleukin-5", published 19 August 1993, assigned to Schering Corporation 
  14. ↑ "Cephalon pays $250M to snare Ception Therapeutics". FierceBiotech.com. 2010-02-23. Archived from the original on 2016-11-21. Retrieved 2016-11-22.
  15. ↑ "Teva to Acquire Cephalon in $6.8 Billion Transaction". Tevapharm.com. Archived from the original on 2016-11-21. Retrieved 2016-11-22.
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