Benralizumab for chronic obstructive pulmonary

Transcription

1 NIHR Innvatin Observatry Evidence Briefing: Nvember 2017 Benralizumab fr chrnic bstructive pulmnary disease (COPD) NIHRIO (HSRIC) ID: 6086 NICE ID: 9196 LAY SUMMARY Chrnic bstructive pulmnary disease (smetimes called chrnic brnchitis r emphysema) is a lung disease that causes difficulties in breathing, mstly due t narrwing f the airways. The main cause f chrnic bstructive pulmnary disease is smking. Symptms f this disease include increased difficulty breathing when active, persistent cugh, and frequent chest infectins. Patients with chrnic bstructive pulmnary disease can have a sudden wrsening f symptms, knwn as an exacerbatin r flare up, which can lead t being admitted t hspital. Benralizumab is a new drug being develped fr the treatment f chrnic bstructive pulmnary disease. It is administered by injectin under the skin and acts by targeting specific prteins that causes the airway t narrw. If benralizumab is licensed fr use in the UK, it culd be a new treatment ptin fr patients with chrnic bstructive pulmnary disease that may imprve quality f life and reduce the number f exacerbatins. This briefing is based n infrmatin available at the time f research and a limited literature search. It is nt intended t be a definitive statement n the safety, efficacy r effectiveness f the health technlgy cvered and shuld nt be used fr cmmercial purpses r cmmissining withut additinal infrmatin. This briefing presents independent research funded by the Natinal Institute fr Health Research (NIHR). The views expressed 1 are thse f the authr and nt necessarily thse f the NHS, the NIHR r the Department f Health.

2 TARGET GROUP Mderate t very severe chrnic bstructive pulmnary disease (COPD); patients with exacerbatin histry. TECHNOLOGY DESCRIPTION Benralizumab is a fully humanized anti interleukin 5 receptr (IL 5R) alpha chain mnclnal antibdy derived frm mice. It binds t the alpha subunit f interleukin 5 receptr and inhibits its actin. Interleukin 5 wrks tgether with ther interleukin receptrs and signalling prteins t induce esinphil mediated inflammatry respnses. Benralizumab exhibits its actin by targeting esinphils and basphils whse functins are driven by Interleukin 5 receptr. It deletes these cells thrugh apptsis inductin and checks the prgressin f the disease. It is based n POTELLIGENT technlgy platfrm, a new hst cell line fr the prductin f recmbinant antibdies. Benralizumab is a new mlecular entity (NME). It is administered subcutaneusly and is intended fr the treatment f mderate t very severe COPD patients with exacerbatin histry. 1 This prduct is nt currently licenced fr any indicatin in the EU r the US. Benralizumab is in late stage clinical develpment in the EU and glbally fr the treatment f asthma, hyperesinphilic syndrme and granulmatsis with plyangiitis. 2 INNOVATION and/r ADVANTAGES If licensed, benralizumab will ffer an additinal treatment ptin fr mderate t severe COPD fr patients with exacerbatin histry wh d nt achieve adequate symptm cntrl with existing agents. AstraZeneca UK Ltd DEVELOPER AVAILABILITY, LAUNCH r MARKETING The Cmmittee fr Medicinal Prducts fr Human Use (CHMP) f the Eurpean Medicines Agency has adpted a psitive pinin, recmmending the marketing authrisatin f benralizumab as an addn maintenance treatment in adult patients with severe esinphilic asthma inadequately cntrlled despite high dse inhaled crticsterids plus lng acting b agnists. 3 PATIENT GROUP BACKGROUND Chrnic bstructive pulmnary disease (COPD) is a treatable (but nt curable) and largely preventable lungs disease with symptms such as cugh, sputum, and increasing breathlessness. 4 It is 2

3 characterized by airflw bstructin which is usually prgressive, nt fully reversible, and des nt change markedly ver several mnths. 5 Airflw bstructin is due t a cmbinatin f airway disease (bstructive brnchilitis) and parenchymal damage (emphysema), resulting frm an enhanced inflammatry respnse t nxius particles r gases, usually frm cigarette smke, but als frm envirnmental and ccupatinal expsures. 4 COPD is the preferred term fr chrnic brnchitis, emphysema, r chrnic bstructive airways disease. 6 Current NICE guidelines establish the fllwing criteria fr COPD diagnsis: 5 Airflw bstructin is defined as a reduced FEV1/FVC rati (where FEV1 is frced expired vlume in 1 secnd and FVC is frced vital capacity), such that FEV1/FVC is less than 0.7. If FEV1 is 80% predicted nrmal a diagnsis f COPD shuld nly be made in the presence f respiratry symptms, fr example breathlessness r cugh. COPD can be characterised by frequent (and smetimes preventable) exacerbatins r flare ups, where there is a rapid and sustained wrsening f symptms beynd nrmal day t day variatins, which can lead t admissin t hspital. Accrding t current NICE guidelines, an exacerbatin is a sustained wrsening f the patient's symptms frm their usual stable state which is beynd nrmal day t day variatins, and is acute in nset. Cmmnly reprted symptms are wrsening breathlessness, cugh, and increased sputum prductin and change in sputum clur. The change in these symptms ften necessitates a change in medicatin. 5 Exacerbatins f COPD ccur at least annually in apprximately 50 60% f patients with mderate/severe COPD. 7 Over time, patients experience increasing breathlessness and mre frequent exacerbatins f respiratry symptms, leading t increasing disability and reduced quality f life. 8 Patients with COPD ften have significant c mrbidities such as heart failure, diabetes, lung cancer, stearthritis, and depressin. 9 Type 2 respiratry failure is bserved in a quarter f COPD patients admitted t hspital. COPD prduces symptms, disability and impaired quality f life which may respnd t pharmaclgical and ther therapies that have limited r n impact n the airflw bstructin. 10 CLINICAL NEED and BURDEN OF DISEASE An estimated 210 millin peple suffer frm COPD wrldwide, and it is predicted t be the third leading cause f death by In the UK, an estimated 1.2 millin peple are living with diagnsed COPD. 12 In terms f diagnsed cases, this makes COPD the secnd mst cmmn lung disease in the UK, after asthma. Arund 2% f the whle ppulatin 4.5% f all peple aged ver 40 live with diagnsed COPD. 12 The prevalence f COPD increases with age (it is rare befre 35 years f age), and is generally higher amng smkers. 13 Accrding t the British Lung Fundatin, that prevalence is grwing. Frm 2008 t 2012 there was a 9% increase. In the UK, 115,000 peple are diagnsed with COPD each year. 12 The UK is amng the tp 20 cuntries fr COPD mrtality wrldwide. In Eurpe, nly Denmark and Hungary have higher death rates fr COPD. In the United States and New Zealand rates are higher 3

4 than in the UK. 12 Fr England, the COPD mrtality rate was higher in the Nrth East and Nrth West f England, cmpared with the UK generally. In thse regins, the relative increase was greater amng females than males. Death rates frm COPD were ntably lwer in the East f England and the Suth West than in ther parts f the UK. 12 In 2010 it was estimated that COPD cst the NHS mre than 800 millin each year, (equivalent t 1.3 millin per 100,000 ppulatin). COPD was respnsible fr 24 millin lst wrking days per annum estimated as csting 2.7 billin. 14 The latest hspital Episdes statistics fr 2016/17 revealed 1,283,972 admissins fr ther COPD (ICD 10 cde J44) and 236,078 day cases. 15 PATIENT PATHWAY RELEVANT GUIDANCE NICE GUIDANCE NICE technlgy appraisal in develpment. Meplizumab fr treating chrnic bstructive pulmnary disease (GID TA10239). Expected date f issue t be cnfirmed. NICE technlgy appraisal. Rflumilast fr treating chrnic bstructive pulmnary disease (TA461). July NICE clinical guideline in develpment. Chrnic bstructive pulmnary disease in ver 16s: diagnsis and management (update) (GID NG10026). Expected Nvember NICE clinical guideline. Chrnic bstructive pulmnary disease in ver 16s: diagnsis and management (CG101). June NICE quality standard. Chrnic bstructive pulmnary disease in adults (QS10). July Updated: February Nne identified NHS ENGLAND and POLICY GUIDANCE OTHER GUIDANCE Glbal Initiative fr Chrnic Obstructive Lung Disease. Glbal strategy fr the diagnsis, management, and preventin f chrnic bstructive pulmnary disease Primary Care Respiratry Sciety UK. Diagnsis and management f COPD in primary care Scttish Intercllegiate Guidelines Netwrk. Chrnic bstructive pulmnary disease services CURRENT TREATMENT OPTIONS High value interventins in the management f COPD include smking cessatin advice, pulmnary rehabilitatin and flu vaccinatin. 5,16 Pharmaclgical treatments include: Beta 2 agnists: Shrt acting beta 2 agnists salbutaml and terbutaline. Lng acting beta 2 agnists salmeterl, frmterl, indacaterl, ldaterl and vilanterl. 4

5 Muscarinic antagnists: Shrt acting muscarinic antagnists ipratrpium. Lng acting muscarinic antagnists titrpium, umeclidinium, aclidinium and glycpyrrnium. Inhaled cmbinatin therapy: Frmterl plus budesnide. Salmeterl plus fluticasne prpinate. Vilanterl flus fluticasne furate. Oral therapy: Oral crticsterid therapy maintenance use f ral crticsterid therapy in COPD is nt nrmally recmmended. Hwever, sme peple with advanced COPD may require maintenance ral crticsterids when these cannt be withdrawn after an exacerbatin. Muclytics carbcisteine. Methylxanthines aminphylline and thephylline. Rflumilast, as an add n t brnchdilatr therapy, is recmmended as an ptin fr treating severe chrnic bstructive pulmnary disease in adults with chrnic brnchitis, nly if: 17 the disease is severe, defined as a frced expiratry vlume in 1 secnd (FEV1) after a brnchdilatr f less than 50% f predicted nrmal, and the persn has had 2 r mre exacerbatins in the previus 12 mnths despite triple inhaled therapy with a lng acting muscarinic antagnist, a lng acting beta 2 agnist and an inhaled crticsterid. Exacerbatins are usually treated with an increase in usual medicatin cmbined with a curse f sterids and/r antibitics. 5 Nn invasive ventilatin significantly reduces mrtality in peple with COPD wh develp type 2 respiratry failure. 18 Pulmnary rehabilitatin, a prgramme f exercise and educatin fr peple with lng term lung cnditins, is als recmmended. 19 EFFICACY and SAFETY Trial Spnsr Status Surce f Infrmatin Lcatin Design Participants TERRANOVA; NCT ; D3251C00004; Phase III AstraZeneca Onging, nt recruiting Trial registry 20 Argentina, Australia, Brazil, Chile, Clmbia, 8 EU cuntries (nt UK); Israel, Mexic, New Zealand, Nrway, Peru, Philippines, Serbia, Taiwan, Thailand, Turkey, Ukraine, United States, and Vietnam Randmised; placeb/cntrlled n=2,255; aged years; male and female; mderate t very severe COPD with Pst Brnchdilatr (BD) FEV1>20% and 65% 2 mderate r 1 severe COPD exacerbatin(s) required treatment r hspitalizatin within 2 52 weeks prir t visit1 5

6 Schedule Fllw up Primary Outcmes Secndary Outcmes Benralizumab subcutaneusly n study week 0 until study week 48 inclusive Active treatment fr 48 weeks, fllw up fr primary utcme measure up t 56 weeks. Annual COPD (Chrnic Obstructive Pulmnary Disease) exacerbatin rate Effect f benralizumab n health status/health related quality f life [ Time Frame: up t 56 weeks ] St. Gerge's Respiratry Questinnaire (SGRQ ), Chrnic Obstructive Pulmnary Disease assessment tl (CAT) Effect f benralizumab n pulmnary functin [ Time Frame: up t 56 weeks ] Pre dse/pre brnchdilatr Frced expiratry vlume in ne secnd (FEV1) at the study centre Effect f benralizumab n respiratry symptms [ Time Frame: up t 56 weeks ] Baseline/Transitinal Dyspnea Index (BDI/TDI) Effect f benralizumab n rescue medicatin use [ Time Frame: up t 56 weeks ] Ttal rescue medicatin use (average puffs/day), recrded by patient using electrnic diary Effect f benralizumab n ncturnal awakenings [ Time Frame: up t 56 weeks ] Number f nights with awakening due t COPD, recrded by patient using electrnic diary Effect f benralizumab n the severity, frequency and duratin f exacerbatins f COPD [ Time Frame: up t 56 weeks ] Exacerbatins f Chrnic Pulmnary Disease Tl (EXACT PRO) Patient reprted Outcme questinnaire Effect f benralizumab n healthcare resurce utilizatin [ Time Frame: up t 56 weeks ] Annual rate f hspitalizatins, cmbined hspitalizatins and emergency department visits, unscheduled visits and healthcare encunters due t COPD Benralizumab cncentratin in serum [ Time Frame: up t 60 weeks ] Pharmackinetics (PK) steady state serum pre dse cncentratin Safety and tlerability f benralizumab [ Time Frame: Frm baseline visit up t 56 weeks ] Adverse Events/ Serius Adverse Events (AE/SAE) Labratry variables 12 lead Electrcardigram (ECG) Physical Examinatin Vital Signs Immungenicity f benralizumab [ Time Frame: up t 60 weeks ] Determinatin f Anti drug antibdies (ADA) develpment Effect f benralizumab n general health status [ Time Frame: up t 56 weeks ] Eurpean Quality f Life 5 Dimensins (EQ 5D 5L) questinnaire Impact f benralizumab n bld esinphil levels [ Time Frame: up t 60 weeks ] Bld esinphils levels Key Results Adverse effects (AEs) Expected Estimated primary cmpletin date April 2018 (Final data cllectin date fr reprting date primary utcme measure) Trial Spnsr Status GALATHEA; NCT ; D3251C00003; Phase III AstraZeneca Onging, nt recruiting 6

7 Surce f Infrmatin Lcatin Design Participants Schedule Fllw up Primary Outcmes Secndary Outcmes Trial registry EU cuntries (incl. UK); Canada, Japan, Krea, Russian Federatin, Suth Africa, Switzerland, and United States Randmised; placeb/cntrlled N=1,656; age years; male and female; mderate t very severe COPD with Pst Brnchdilatr (BD) FEV1>20% and 65% mderate r 1 severe COPD exacerbatin(s) required treatment r hspitalizatin within 2 52 weeks prir t visit1. Benralizumab administered subcutaneusly (regimen t specified) Active treatment perid N/R, verall fllw up perid f 56 weeks Annual COPD (Chrnic Obstructive Pulmnary Disease) exacerbatin rate Evaluatin f the effect f benralizumab n health status/health related quality f life [ Time Frame: up t 56 weeks ] St. Gerge's Respiratry Questinnaire (SGRQ), Chrnic Obstructive Pulmnary Disease assessment tl (CAT) Evaluatin f the effect f benralizumab n pulmnary functin [Time Frame: up t 56 weeks ] Pre dse/pre brnchdilatr Frced expiratry vlume in ne secnd (FEV1) at the study centre Evaluatin f the effect f benralizumab n respiratry symptms [Time Frame: up t 56 weeks] Baseline/Transitinal Dyspnea Index (BDI/TDI) Evaluatin f the effect f benralizumab n rescue medicatin use [Time Frame: up t 56 weeks] Ttal rescue medicatin use (average puffs/day), recrded by patient using electrnic diary Evaluatin f the effect f benralizumab n ncturnal awakenings [Time Frame: Up t 56 weeks] Number f nights with awakening due t COPD, recrded by patient using electrnic diary. Evaluatin f the effect f benralizumab n the severity, frequency and duratin f Exacerbatins f Chrnic Pulmnary Disease Tl (EXACT PRO) Patient reprted Outcme questinnaire defined events [Time Frame: Up t 56 weeks] Exacerbatins f Chrnic Pulmnary Disease Tl (EXACT PRO) Patient reprted Outcme questinnaire Evaluatin f the effect f benralizumab n healthcare resurce utilizatin due t COPD [Time Frame: up t 56 weeks] Annual rate f hspitalizatins, cmbined hspitalizatins and emergency department visits, unscheduled visits and healthcare encunters due t COPD Evaluatin f the pharmackinetics parameters f benralizumab. [Time Frame: up t 60 weeks] Pharmackinetics (PK) steady state serum predse cncentratin Assessment f the safety and tlerability f benralizumab [Time Frame: Frm baseline visit up t 56 weeks] Adverse Events/ Serius Adverse Events (AE/SAE) Labratry variables 12 lead Electrcardigram (ECG) Physical Examinatin Vital Signs Evaluatin f the immungenicity f benralizumab [Time Frame: up t 60 weeks] Determinatin f Anti drug antibdies (ADA) Key Results Adverse effects (AEs) 7

8 Expected reprting date Estimated primary cmpletin date April 2018 (final cllectin date fr primary utcme measure) ESTIMATED COST and IMPACT COST The cst f benralizumab is nt yet knwn. IMPACT SPECULATIVE IMPACT ON PATIENTS AND CARERS Reduced mrtality/increased length f survival Reduced symptms r disability Other N impact identified IMPACT ON HEALTH and SOCIAL CARE SERVICES Increased use f existing services Decreased use f existing services Re rganisatin f existing services Need fr new services Other Nne identified IMPACT ON COSTS and OTHER RESOURCE USE Increased drug treatment csts Reduced drug treatment csts Other increase in csts Other reductin in csts Other: uncertain unit cst cmpared t existing treatments Nne identified OTHER ISSUES Clinical uncertainty r ther research questin identified Nne identified 8

9 REFERENCES 1 UK Pharma Scan. Benralizumab. Available frm [Accessed 31 Octber 2017, lg in required] 2 Glbal Data. Benralizumab. Available frm [Accessed 1 Nvember 207, lg in required] 3 AstraZeneca. Benralizumab receives psitive EU CHMP pinin fr severe, uncntrlled esinphilic asthma. 10 Nvember Available frm centre/press releases/2017/benralizumab receives psitive eu chmp pinin fr severe uncntrlled esinphilic asthma html [Accessed 24 Nvember 2017] 4 GOLD. Glbal strategy fr the diagnsis, management, and preventin f chrnic bstructive pulmnary disease (updated 2015).Glbal Initiative fr Chrnic Obstructive Lung Disease (GOLD). 5 Natinal Institute fr Health and Care Excellence. Chrnic bstructive pulmnary disease in ver 16s: diagnsis and management. Clinical Guideline 101. June Available frm [Accessed 31 Octber 2017] 6 Clinical Knwledge Summaries. Chrnic bstructive pulmnary disease. September Available frm bstructive pulmnary disease [Accessed 31 Octber 2017] 7 Jrdan R, Majthi S, Heneghan N et al. Supprted self management fr patients with mderate t severe chrnic bstructive pulmnary disease (COPD): an evidence synthesis and ecnmic analysis. Health Technlgy Assessment 2015; di: /hta Glbal Initiative fr Chrnic Obstructive Lung Disease. Glbal strategy fr the diagnsis, management, and preventin f chrnic bstructive pulmnary disease. [Accessed 31 Octber 2017] 9 Primary Care Respiratry Sciety UK. Diagnsis and management f COPD in primary care. Available frm uk.rg/sites/pcrs uk.rg/files/copdquickguide2015final_0.pdf [Accessed 31 Octber 2017] 10 Natinal Institute fr Health and Care Excellence. Wrking definitin f COPD. Available frm definitin f COPD [Accessed 31 Octber 2017] 11 AstraZeneca. Benralizumab Phase II COPD study published in The Lancet Respiratry Medicine Available frm centre/press releases/2014/benralizumab study lancetrespiratry medicine html# [Accessed 30 Octber 2017] 12 British Lung Fundatin. Numbers f peple diagnsed with COPD. Available frm [Accessed 1 Nvember 2017] 13 Natinal Institute fr Health and Care Excellence. Prpsed health technlgy appraisal. Meplizumab fr treating chrnic bstructive pulmnary disease. Draft scpe (pre referral). Available frm ta10239/dcuments/draft scpe pre referral [Accessed 31 Octber 2017] 14 Department f Health. Facts abut COPD. Available frm D/DH_ [Accessed 30 Octber 2017] 15 NHS Digital. Hspital Admitted Patient Care Activity, Available frm [Accessed 23 Octber 2017] 16 Natinal COPD Audit Prgramme. COPD in England Finding the measure f success. Natinal Chrnic Obstructive Pulmnary Disease (COPD) Audit Prgramme: Primary care reprt fr England Ryal Cllege f Physicians: Lndn, Natinal Institute fr Health and Care Excellence. Rflumilast fr treating chrnic bstructive pulmnary disease. TA461. Available frm [Accessed 20 Nvember 2017] 18 NHS England. Overview f ptential t reduce lives lst frm Chrnic Obstructive Pulmnary Disease (COPD). cntent/uplads/2014/02/rm fs 6.pdf [Accessed 31 Octber 2017] 19 British Lung Fundatin. Pulmnary rehabilitatin. fr yu/keepactive/pulmnary rehabilitatin [Accessed 31 Octber 2017] 9

10 20 ClinicalTrials.gv. Efficacy and Safety f Benralizumab in Mderate t Very Severe Chrnic Obstructive Pulmnary Disease (COPD) With Exacerbatin Histry (TERRANOVA). Available frm [Accessed 31 Octber 2017] 21 ClinicalTrials.gv. Benralizumab Efficacy in Mderate t Very Severe Chrnic Obstructive Pulmnary Disease (COPD) With Exacerbatin Histry (GALATHEA). Available frm [Accessed 31 Octber 2017] 10