COPD presentation

BREO ELLIPTA IN MODERATE-SEVERE COPD

Kathy Chow

Amcare Rotation

Navel Hospital Camp Pendleton

August 5, 2013

OUTLINE

Patient case Epidemiology Pathophysiology Risk factors Diagnosis COPD Classifications/Treatment Breo Ellipta and trials On the market comparisons

PATIENT CASE

57yo male presents to pharmacy clinic post ER admission of COPD exacerbation

CC SOB and recurrent hospitalizations

PMH Been to emergency department 5 times last year

and admitted twice. COPD for 10 years

SH 50 pack years, but quit 2 years ago.

PATIENT CASE

Current medications: Tiotropium 1 puff (18mcg) QD Albuterol Inhaler PRN for SOB. Oxygen while sleeping (8hrs/night)

Vital signs WNL

Labs FEV1/FVC = 0.46 Absolute FEV1 = 45% of predicted.

What changes would you make to the medication regimen?

EPIDEMIOLOGY

4th leading cause of death in the US Estimated annual treatment costs exceeding

$30 billion(health and indirect cost combined) A major cause of disability (11th leading cause

of disability worldwide) Current projections by 2020.

COPD will be the 5th leading cause of disability worldwide, behind only ischemic heart disease, major depression, traffic accidents, and cerebrovascular disease

Koda Kimble

PATHOPHYSIOLOGY

COPD DEFINITIONS

Chronic BronchitisChronic cough for at least 3 months for 2 consecutive years

Inflammation of the bronchioles (where asthma, CHF, reflux is ruled out)

EmphysemaAlveolar wall destruction and airspace enlargement

Koda Kimble

RISK FACTORS

Cigarette smoking (current or past history)Most pts have at least 20 pack year history

Cofactors Occupational dusts and chemicals Indoor and outdoor air pollutionRespiratory viruses

α1-antitrypsin deficiency(<2% with emphysema)Lack of protease inhibitor to prevent

breakdown of elastin

Koda Kimble

DIAGNOSIS

Risk factors Clinical symptoms Spirometry (gold standard) Chest X ray Pulse oximetry

Koda Kimble

COPD CLASSIFICATIONClassificatio

n Spirometry

ResultsSymptoms

Mild FEV1/FVC <0.70

FEV1 ≥80%

predicted

Minimal SOB

Moderate FEV1/FVC <0.70

50% ≤FEV1<80%

predicted

moderate or severe shortness of breath on exertion, with or without cough, or

sputum

Gold guidelines

COPD CLASSIFICATIONClassificatio

n Spirometry Results Symptoms

Severe FEV1/FVC <0.70

30% ≤FEV1 <50%

predicted

Severe shortness of breath, with or without cough, or sputum- often

with repeated exacerbations which

usually impact quality of life, reduced exercise

capacity, fatigue.

Very severe FEV1/FVC <0.70

FEV1 <30% predicted

or FEV1 <50%

predicted + chronic respiratory failure

Impaired QOL due to SOB- possible

exacerbations may even be life threatening at

times

Gold guidelines

TREATMENT

Patient

Group

First choice Alternative Choice Other possible

treatments

Mild SAAC prnor

SABA prn

LAACor

LABAor

SABAand

SAAC

Theophylline

Mod LAACor

LABA

LAAC and LABA SABA and/or SAAC

Theophylline

Gold guidelines

TREATMENTPatient Group

First choice

Alternative Choice Other possible

treatments

Severe ICS+ LABAOR

LAAC

LAAC + LABAOR

LAAC + PDE4IOR

LABA + PDE4I

SABA and/orSAAC

Theophylline

Very Severe

ICS + LABAand/orLAAC

ICS + LABA +LAACor

ICS + LABA + PDE4Ior

LAAC + LABAor

LAAC + PDE4I

Carbocysteine

SABAand/orLAAC

Theophylline

Gold guidelines

BREO ELLIPTA IN MODERATE TO SEVERE COPD

Cost per month: $267.68 Approved May 2013 MOA

Vilanterol (LABA)+ Fluticasone Furoate (ICS) half life = 24 hrs

Side Effects Nasopharyngitis (9%) URTI (7%) Oral Candidiasis (5%)

Administration Once daily dry powder inhaler Swish and spit with water after administration

Pharmacist Letter, Lexicomp, Breo Ellipta PI

BREO ELLIPTA METHODS

2 week run in period 24 week (10 clinic visits in between) 7 day telephone follow up. Multicenter, RCT, double blind, placebo

controlled Eligible subjects were then randomized

(1:1:1:1:1) FF/VI 100/25 FF/VI 50/25 FF 100ug VI 25ug, Placebo

Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.

BREO ELLIPTA INCLUSION CRITERIA

≥40 years old COPD Diagnosis Smoking history of ≥10 pack-years Post bronchodilator FEV1/FVC ≤0.7 Post bronchodilator FEV1≤70% predicted ≥2 on mMRC (modified medical research

council dyspnea scale)


BREO ELLIPTA EXCLUSION CRITERIA Asthma diagnosis Non-COPD respiratory disorders Lung volume reduction surgery within 12 months of visit 1 Clinically significant abnormal EKG Acute worsening of COPD requiring corticosteroids or

antibiotics or treatment prescribed by a physician within 6 weeks prior to visit 1

Hospitalization due to poorly controlled COPD within 12 weeks prior to visit 1

Lower respiratory tract infection requiring antibiotics within 6 weeks prior to visit 1

Long term oxygen therapy or nocturnal oxygen therapy (≥12hr/day)

Non compliance (fail to complete 4 out of 7 daily diary card, using prohibited COPD meds)


BREO ELLIPTA STATISICAL ANALYSIS

To achieve 90% power and α risk of 0.05, a sample size of at least 146 per arm was required to detect treatment difference of 100ml

ITT, all subjects were accounted for if they had at least 1 dose of the study med


BREO ELLIPTA STUDY POPULATION

Treatment 100/25ug Placebo

Start with N=206 Adverse events =14Lack of efficacy = 12Exacerbation = 12

Other dropped due to protocol deviation, lost to f/u, withdrew consent, investigator discretion

Completed n = 151

Start with N=207Adverse events n = 15Lack of efficacy n = 20Exacerbation n=17

Other dropped due to protocol deviation, lost to f/u, withdrew consent, investigator discretion

Completed n=138


BREO ELLIPTA STUDY CHARACTERISTICS

Treatment 100/25ug Placebo

Subject CharacteristicsAge = 62Male = 68%Race = White 75%, Asian 20%Current smoker = 54%Pack yr = 46Emphysema = 61%Chronic Bronchitis = 62%Pre treatment lung functions were similar.

Similar to treatment group


BREO ELLIPTA ENDPOINT

FF/VI 100/25ugImproved weighted mean FEV1 at

168 weeks by 173ml 95%CI(123-224ml) p = <0.001

Trough FEV1 by 115ml 95%CI (60-169ml) p=<0.001

All secondary endpoints were not statistically significant.


BREO ELLIPTA SAFETY OUTCOME

Adverse Event

Treatment Placebo

Nasopharyngitis

22(11%) 14(7%)

URTI 21(10%) 8(4%)

Headache 18(9%) 5(2%)

Oropharyngeal Candidiasis

6(3%) 2(<1%)


BREO ELLIPTA CONCLUSIONS

FF/VI provides significant sustained bronchodilation at 24 weeks with rapid onset of action and treatments were well tolerated

Longer term studies required to determined COPD exacerbations


ON THE MARKET…. Medication NameCost per 30 day

Doses Onset Sig Side Effects

Budesonide /Formoterol/(Symbicort)$235.53

80/4.5ug, 160/4.5ug

10-20 min BID Headache (7-11%)Nasopharyngitis (7-11%)URTI (4-11%)Oral Candidiasis (1-6%)

Salmeterol/Fluticasone Propionate(Advair Diskus)$341.81

100/50ug, 250/50ug, 500/50ug

10-20 min BID Headache (12-27%)URTI (16-27%)Pharyngitis (9-13%)Oral Candidiasis (1-4%)Throat Irritation (7-9%)

Vilanterol/Fluticasone Propionate (Breo Ellipta)$267.68

100/25ug

10-20 min QD Headache (7%)Nasopharyngitis (9%)URTI (7%)Oral Candidiasis (5%)

Lexicomp, Breo Ellipta PI, pharmacist letter

BACK TO PATIENT CASE CC

SOB and recurrent hospitalizations

PMH Been to emergency department 5 times last year and

admitted twice. COPD for 10 years

SH 50 pack years, but quit 2 years ago.

Labs FEV1/FVC = 0.46 Absolute FEV1 = 45% of predicted.

Current meds Tiotropium 1 puff (18mcg) QD Albuterol Inhaler PRN for SOB

What is the plan?

REFERENCES "Inhalers for COPD." Pharmacist Letter. Therapeutic

Research Center, Aug. 2013. Web. Aug. 2013. “Breo Ellipta Prescribing Information."

GlaxoSmithKline, 2013. Web. 28 July 2013."News & Events From Around the World." Global Initiative for Chronic Obstructive Lung Disease RSS.

03 Aug. 2013.Koda Kimble COPD Uptodate stable COPD Edward M. Kerwin “A randomized trial of fluticasone

furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.

Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. Supplementary online material. January 2013. Accessed July 2013.

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