Zdravilo Fasenra je v klinični raziskavi faze IIIb PONENTE omogočilo opustitev peroralnih glukokortikosteroidov pri večini bolnikov, ki so imeli astmo, odvisno od teh zdravil
V največji klinični raziskavi o zmanjševanju odmerka steroidov pri težki astmi doslej je uporabo peroralnih glukokortikosteroidov opustilo 62 % bolnikov.
Primarni cilj klinične raziskave je pokazal, da so pri 62 % bolnikov dosegli popolno ukinitev dnevne uporabe OGK. Drugi primarni cilj pa je pokazal, da so pri 81 % bolnikov dosegli popolno ukinitev OGK ali pa so lahko zmanjšali dnevni odmerek OGK na 5 mg ali manj, kadar nadaljnje zmanjšanje odmerka ni bilo mogoče zaradi insuficience delovanja nadledvičnih žlez. Oba omenjena primarna opazovana dogodka sta ob ohranjenem nadzoru nad astmo trajala vsaj štiri tedne. V klinično raziskavo PONENTE je bilo vključenih skoraj 600 bolnikov iz Evrope, Severne Amerike, Južne Amerike in Tajvana.
Mene Pangalos, izvršni podpredsednik oddelka raziskav in razvoja bioloških zdravil, je dejal: "Trenutno se v svetu približno 13,5 milijona ljudi s težko astmo opira na peroralne glukokortikosteroide za nadzor nad poslabšanji bolezni in preprečevanje hospitalizacij. Vendar pa lahko prekomerno zanašanje na peroralne glukokortikosteroide predstavlja pomembno tveganje za zdravje bolnikov in povzroči dodatno obremenitev zdravstvenega sistema. Ti podatki dodatno podpirajo klinični profil zdravila Fasenra pri opustitvi uporabe peroralnih glukokortikosteroidov v širši populaciji bolnikov s težko astmo."
Klinična raziskava PONENTE dopolnjuje predhodne podatke o zmanjševanju odmerka OGK iz klinične raziskave faze III ZONDA, in sicer z uporabo hitrejšega režima postopnega zmanjševanja odmerkov glukokortikosteroidov pri bolnikih, pri katerih ni prišlo do nezadostnega delovanja nadledvičnih žlez. V klinični raziskavi PONENTE je bilo vzdrževalno obdobje daljše, trajalo je približno 24 do 32 tednov, kar kaže na trajnejše zmanjšanje odmerka OGK ob nadzorovani astmi, kot je bilo to opaženo v klinični raziskavi ZONDA in vseh drugih objavljenih raziskavah z biološkimi zdravili.8,9 Rezultati o neželenih učinkih in prenašanju zdravila Fasenra so bili v klinični raziskavi PONENTE skladni z znanim podatki zdravila. Rezultati klinične raziskave bodo predstavljeni na prihajajočih strokovnih kongresih.
Zdravilo Fasenra je trenutno odobreno kot dodatno vzdrževalno zdravljenje hude eozinofilno astmo v ZDA, EU, na Japonskem in v drugih državah in je odobreno za samoinjiciranje v ZDA, EU in drugih državah. Januarja 2020 je družba AstraZeneca objavila, da je poleg težke astme še osem eozinofilnih bolezni, pri katerih preizkušajo zdravilo Fasenra.
OPOMBE ZA UREDNIKE
Severe asthma
Asthma affects approximately 339 million individuals worldwide.1,2 Approximately 10% of asthma patients have severe asthma, which may be uncontrolled despite high dosages of standard of care asthma controller medicines and can require the long-term use of OCS.2,10,11 Severe, uncontrolled asthma is debilitating and potentially fatal, with patients experiencing frequent exacerbations and significant limitations on lung function and health-related quality of life.2,11,12 Severe, uncontrolled asthma has a greater risk of mortality than severe asthma.10 70% or more of people with severe asthma have elevated counts of eosinophils, white blood cells that are a normal part of the immune system and can drive airway inflammation in some patients.10,11,13,14
Severe, uncontrolled asthma can lead to a dependence on OCS, with cumulative steroid exposure leading to serious short- and long-term adverse effects including weight gain, diabetes, osteoporosis, glaucoma, anxiety, depression, cardiovascular disease immunosuppression and adrenal insufficiency.5-7 OCS over-reliance can also place additional strain on health systems; a UK analysis identified OCS-dependent asthma patients have an average of 43% greater associated direct healthcare treatment costs than patients not receiving maintenance OCS.15
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones.16,17 Steroid hormones are important to help control metabolism, inflammation, immune functions and salt and water balance, among other critical functions.17 Adrenal insufficiency can develop as a result of taking chronic OCS and may persist following steroid reduction or discontinuation, potentially causing serious clinical consequences including shock, seizure, coma and even death in cases of an acute adrenal crisis.16,17
PONENTE
PONENTE is a multicentre, open-label, single-arm, Phase IIIb trial to evaluate the efficacy and safety of reducing daily OCS use after initiation of 30 mg dose of Fasenra administered subcutaneously (SC) in adult patients with severe eosinophilic asthma on high-dose inhaled corticosteroids (ICS) plus long-acting beta2-agonist (LABA) and long-term use of OCS therapy with or without additional asthma controller(s). Patients recruited into the study had been on maintenance OCS dose of ≥5 mg of prednisone for at least three months and had a baseline peripheral blood eosinophil count of ≥150 cells/μL or baseline eosinophils below 150 cells/μL with a documented eosinophil count of ≥300 cells/μL in the past 12 months. The treatment period consisted of a four-week induction phase with no OCS adjustments, a variable OCS tapering phase and an ongoing 24-32-week maintenance phase.8,18
The primary outcome measures of the trial were the proportion of patients achieving a 100% reduction in daily OCS dose and the proportion of patients achieving a 100% reduction or a daily OCS dose of ≤5 mg if the reason for no further OCS reduction was adrenal insufficiency, both sustained for at least four weeks without worsening of asthma.8,18
Compared to published trials, PONENTE has a personalised OCS tapering schedule that allows for more rapid OCS tapering from high OCS doses, followed by an assessment of the adrenal function as part of decision-making to manage the risk of adrenal insufficiency. PONENTE also has a significantly longer maintenance phase, (approximately 24-32 weeks versus four weeks for published trials of other biologics) allowing assessment of the durability of OCS reduction.8,18
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).19,20
Fasenra is in development for other eosinophilic diseases and chronic obstructive pulmonary disease.21-25 The 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 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/Nasdaq: 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 & 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
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