O-STA

Zdravilo Fasenra je v klinični raziskavi faze III OSTRO pri bolnikih s kroničnim rinosinusitisom z nosnimi polipi doseglo oba primarna cilja; zmanjšanje velikosti nosnega polipa in zamašitev nosu

Prvi rezultati klinične raziskave faze III OSTRO so pokazali, da je zdravilo Fasenra (benralizumab) podjetja AstraZenece v primerjavi s placebom pokazalo statistično značilno izboljšanje velikosti nosnih polipov in zamašitve nosu pri bolnikih s kroničnim rinosinusitisom z nosnimi polipi (CRSwNP - chronic rhinosinusitis with nasal polyps).

Zdravilo Fasenra je pokazalo statistično značilno izboljšanje popolne endoskopske ocene nosnega polipa (NPS - nasal polyp score) in ocene zamašitve nosu (NBS - nasal blockage score) v primerjavi s placebom pri bolnikih s težko obojestransko nosno polipozo, ki so imeli simptome kljub standardnemu zdravljenju. Standard zdravljenja je nosni kortikosteroid in predhodna operacija in / ali uporaba sistemskega kortikosteroida. Vrednotenje NPS je temeljilo na endoskopski oceni velikosti polipa, ki jo je postavil raziskovalec. Vrednotenje NBS pa na dnevniku simptomov, o katerem so poročali bolniki.

CRSwNP je vnetna bolezen, povezana z zvišano koncentracijo eozinofilcev v zgornjih dihalih, za katero so značilni benigni izrastki, imenovani nosni polipi.1,2 Polipi lahko povzročijo zamašitev in izcedek iz nosu, motnje ali izgubo vonja, motnje spanja in druge škodljive učinke na kakovost življenja.3-5

Profesor Claus Bachert, vodja oddelka za otorinolaringologijo in predstojnik raziskovalnega laboratorija za zgornja dihala, Univerzitetne bolnišnice v Gentu v Belgiji, ki je glavni raziskovalec raziskave, je dejal: "Kronični rinosinusitis z nosnimi polipi je težko zdraviti. Osnovni vzroki kot tudi naravna zgodovina bolezni niso v celoti poznani. Rezultati raziskave OSTRO kažejo, da lahko mehanizem delovanja zdravila Fasenra, deplecija eozinofilcev, koristi bolnikom pri tem pogosto izčrpavajočem stanju stanjem."

Mene Pangalos, izvršna podpredsednica, BioPharmaceuticals R&D, je dejala: "Bolniki s kroničnim rinosinusitisom z nosnimi polipi znatno trpijo zaradi zamašenega nosu in zmanjšane kakovosti življenja. Trenutna zdravila, kot so nosni ali peroralni kortikosteroidi in kirurški posegi za odstranjevanje polipov, ne ustrezajo v celoti potrebam bolnikov. Podatki raziskave OSTRO kažejo, da lahko zdravilo Fasenra koristi bolnikom z nosnimi polipi. Veselimo se, da bomo pripravili popolno analizo in rezultate predstavili na prihajajočem zdravniškem kongresu."

Neželeni učinki in prenašanje zdravila Fasenra v tej klinični raziskavi so bili v skladu z do sedaj znanimi podatki o zdravilu.

Zdravilo Fasenra je trenutno odobreno kot dodatno vzdrževalno zdravljenje hude eozinofilne astme v ZDA, EU, na Japonskem in v drugih državah ter je odobreno za samoinjiciranje v ZDA, EU in drugih državah.

OPOMBE ZA UREDNIKE

Chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by persistent inflammation of the mucous membrane lining the nasal passages and sinuses accompanied by benign growths, called nasal polyps.6,7 Nasal polyps can block nasal passages and lead to breathing problems, reduction in the sense of smell, nasal discharge, sleep disturbance and other adverse effects on quality of life.3-5 The disease is associated with elevated levels of eosinophils, a type of white blood cell, accumulating in the upper respiratory tract.2

Current treatments for nasal polyps include intranasal or oral corticosteroids (OCS) and surgery to remove polyps, but these often do not address the underlying cause of the disease and the need for repeated interventions can be high. Since 2019, other biologic medicines have been approved or recommended to treat nasal polyps.4,10

OSTRO is part of AstraZeneca's clinical trial programme for Fasenra in CRSwNP which also includes the ongoing Phase III ORCHID trial, among others.11

OSTRO

OSTRO is a randomised, double-blinded, multi-centre, parallel-group, 56-week Phase III trial to evaluate the efficacy and safety of Fasenra compared to placebo in patients with nasal polyposis.12 Fasenra was evaluated in patients, regardless of blood eosinophil count with or without asthma, who were symptomatic despite SoC therapy, including current use of INCS and prior surgery and/or use of systemic corticosteroids. Patients were randomised to receive either Fasenra 30mg or placebo subcutaneously every four weeks for the first three doses and every eight weeks thereafter.12

The primary outcome measures of the trial were: the effect of Fasenra on nasal polyp burden, assessed by change from baseline in endoscopic total NPS, at week 40 compared to placebo; the effect of Fasenra on patient-reported nasal blockage, assessed by change from baseline in mean NBS, at week 40 compared to placebo. OSTRO involved 413 patients in Europe and North America.12

Fasenra

Fasenra (benralizumab) is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis (programmed cell death).13,14

Fasenra is in development for other eosinophilic diseases and chronic obstructive pulmonary disease.15-19 The US Food and Drug Administration granted Orphan Drug Designation for Fasenra for the treatment of eosinophilic granulomatosis with polyangiitis in 2018, and hypereosinophilic syndrome and eosinophilic oesophagitis in 2019.

Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology is one of AstraZeneca's three therapy areas and is a key growth driver for the Company.

Building on a 50-year heritage, AstraZeneca is an established leader in respiratory care across inhaled and biologic medicines. AstraZeneca aims to transform the treatment of asthma and chronic obstructive pulmonary disease (COPD) by eliminating preventable asthma attacks across all severities and removing COPD as a leading cause of death through earlier, biology-led treatment. The Company's early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell repair processes in disease and neuronal dysfunction.

With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immune-driven diseases. The Company's growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential in rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology and systemic eosinophilic-driven diseases. AstraZeneca's ambition in immunology is to achieve disease control and ultimately clinical remission in targeted immune-driven diseases.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal and Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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References

  1. American Academy of Allergy Asthma & Immunology. Nasal Polyps. Available at: https://www.aaaai.org/conditions-and-treatments/library/allergy-library/nasal-polyps.[Last accessed: September 2020].

  2. Fujieda S Imoto Y, Kato Y, et al. Eosinophilic chronic rhinosinusitis. Allergology Int. 2019; 68 (4): 403-412.

  3. Hopkins C. Chronic Rhinosinusitis with Nasal Polyps. N Engl J Med. 2019; 381 (1): 55-63.

  4. Stevens WW, Schleimer RP, Kern RC. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016; 4 (4): 565-572.

  5. Abdalla S, Alreefy H, Hopkins C. Prevalence of sinonasal outcome test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales National prospective audit. Clin Otolaryngol. 2012; 37 (4): 276-282.

  6. Bachert C, Akdis CA. Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2016; 4 (4): 621-628.

  7. Newton JR, Ah-See KW. A review of nasal polyposis. Ther Clin Risk Manag. 2008; 4 (2): 507-512.

  8. Ramirez GA, Yacoub MR, Ripa M, et al. Eosinophils from physiology to disease: a comprehensive review. Biomed Res Int. 2018; 9095275.

  9. Gelardi M, Piccininni K, Quaranta A, et al. Olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps is associated with clinical-cytological grading severity. Acta Otorhinolaryngol Ital. 2019;39:329-335.

  10. CHMP Opinion. Xolair. Available at: https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-xolair-ii-101_en.pdf. [Last accessed: September 2020].

  11. Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID). Available at: https://clinicaltrials.gov/ct2/show/NCT04157335. [Last accessed: September 2020].

  12. Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab for Patients With Severe Nasal Polyposis (OSTRO). Available at: https://clinicaltrials.gov/ct2/show/NCT03401229. [Last accessed: September 2020].

  13. Kolbeck R, Kozhich A, Koike M, et al. MEDI-563, a humanized anti-IL-5 receptor a mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010; 125 (6): 1344-1353.e2.

  14. Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016; 111: 21-29.

  15. Clinicaltrials.gov. Effect of Benralizumab in Atopic Dermatitis. Available at: https://clinicaltrials.gov/ct2/show/NCT03563066 [Last accessed: September 2020].

  16. AstraZeneca data on file (MESSINA trial).

  17. Clinicaltrials.gov. A Study to Evaluate if Benralizumab Compared to Mepolizumab May be Beneficial in the Treatment of Eosinophilic Granulomatosis With Polyangiitis (EGPA) (MANDARA). Available at: https://clinicaltrials.gov/ct2/show/NCT04157348. [Last accessed: September 2020].

  18. Clinicaltrials.gov. A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON). Available at: https://clinicaltrials.gov/ct2/show/NCT04191304 [Last accessed: September 2020].

  19. Clinicaltrials.gov. Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations (RESOLUTE). Available at: https://clinicaltrials.gov/ct2/show/NCT04053634 [Last accessed: September 2020].

Adrian Kemp

Company Secretary

AstraZeneca PLC