Center for Outcomes Research and Economic
Evaluation for Health (C2H), National Institute of
Public Health (NIPH) | URL: http://c2h.niph.go.jp

March 31, 2021

[C2H1901] Summary of cost-effectiveness evaluation of
Fluticasone/Umeclidinium/Vilanterol (Trelegy Ellipta)
1. Indications
Chronic obstructive pulmonary disease (COPD) [chronic bronchitis and pulmonary
emphysema]
2. Price of drug
Trelegy Ellipta 100 was reimbursed from May 2019 for JPY 4183.5 (14 doses) and
JPY 8853.8 (30 doses) (as of March 2021). The price was calculated by a similar
efficacy comparison method with a usefulness premium of 10%. This product wasdesignated as a H1 cost-effectiveness evaluation item.
3. Scope of cost-effectiveness evaluation
This product is enabled to perform triple therapy (ICS/LAMA/LABA) of COPD by one
dose, not two doses. The scope of evaluation agreed upon at the first session of theExpert Committee of Cost-Effectiveness Evaluation (ECCEE) is described hereafter.
The manufacturer insisted the evaluation should be based on the ITT population ofthe randomized IMPACT trial. ECCEE agreed that evaluation should be performedbased on the IMPACT trial. However, background of patients enrolled in IMAPCT trial
had variety in terms of prior treatment they received. Because of it, ECCEE thought
it was difficult to interpret the results of ITT population of the IMPACT trial. Therefore
ECCEE decided that evaluation was performed every sub-population as follows; ITTpopulation was divided into population C to L by prior treatment and eosinophil count,which reflected allergic symptoms. The cut off value of eosinophil count was 100/μL.

150/μL was also used as a sensitivity analysis. In addition, ECCEE agreed thatexacerbation of COPD should be used as the outcome when additional benefitsof Fluticasone/Umeclidinium/Vilanterol (FF/UMEC/VI) was evaluated.

Target population
Prior

Detailed priortreatment

treatment

Eosinophil count<100/μL

Comparator≥100/μL
MITT (Triple

MITT (Triple
Triple therapy

ABdoses)therapy by twodoses)

Doubletherapy

ICS/LABA

Double therapy(LAMA/LABA)
or single therapy
Single therapy

LAMAOthers

therapy by twoCD

ICS/LABAEF

LAMA/LABAGHICS/LABA

IJ

LAMA/LABAKLICS/LABA

No evaluation-MITT: Multiple Inhaler Triple Therapy
ICS: Inhaled corticosteroid
LABA: Long-Acting Beta2-Agonist
LAMA: Long-Acting Muscarinic Antagonist
4. Evaluation of additional benefits
Two non-inferiority trials were detected (207608 trial and 207609 trial) for evaluationof population A and B. Regarding other populations, no randomized control trials werefound except the IMPACT trial, the manufacturer submitted. From these data, themanufacturer interpreted FF/UMEC/VI has additional benefit to all the population
except population A and B. However the academic technology assessment groupsubmitted the following report. The views of the academic group was agreed at thethird session of ECCEE.
・ Population A and B: 207608 trial and 207609 trial proved non inferiority of
FF/UMEC/VI to MITT. FF/UMEC/VI does not have additional benefit to population Aand B.
・ Population C and D: Population C and D patients of the IMPACT trial who received
prior triple therapy were randomly allocated to the double therapy group,
independently from clinical indication (random stepdown of LAMA). Because
stepdown is not randomly selected in the actual clinical practice, the results of
IMPACT trial could not be applied to our evaluation. On the other hand, stepdown ofLAMA is not generally performed in the clinical practice. Therefore there were nocomparative trial data on stepdown of LAMA. Considering them, the views ofacademic group was “Unable to analyze”.
・ Population E and F: Similarly with population C and D, population E and F patientsof in the IMPACT trial who received prior triple therapy were randomly allocated todouble therapy, independently from clinical indication (random stepdown of ICS).
Because stepdown is not randomly selected in the actual clinical practice, the resultsof IMPACT trial could not be applied to our evaluation. On the other hand, according
to the meta-analysis of clinical trials which evaluated stepdown of ICS (COSMIC trial,WISDOM trial, INSTEAD trial and SUNSET trial), it suggested that stepdown of ICS
did not relate with the increasing risk of exacerbation. Therefore FF/UMEC/VI does
not have additional benefit to population E and F.
・ Population G, H, J, K and L: Based on the subgroup analysis of the IMPACT trial,risk ratio of moderate or severe exacerbation was less than 1 (significant in some

populations and not significant in others). These results were not changed by asensitivity analysis, which used a cut off value of eosinophil count as 150/μL.
Therefore FF/UMEC/VI have additional benefit to these populations
・ Population I: Subgroup analysis of the IMPACT trial indicated that the only
population I’s risk ratio of moderate or severe exacerbation exceeded 1, different
from other populations. In addition, clinical implication was not clear to the patientswith low eosinophil count, who received LAMA or LAMA/LABA without ICS based on
the assessment of clinicians. This result was supported by a sensitivity analysis,

which used a cut off value of eosinophil count as 150/μL. Therefore FF/UMEC/VI
does not have additional benefit to population I.
5. Result of cost-effectiveness analysis
For population A and B, the manufacturer assumed the clinical effectiveness was thesame and performed the cost minimization analysis. For population C-L, themanufacturer did cost-effective analysis using Galaxy COPD model. The model canestimate ICER by inputting the difference of FEV1 between two groups. It used somerisk equations made by foreign epidemiological studies.
The academic group revised the economic model based on the following
issues.
・ For populations to which FF/UMEC/VI does not have additional benefit, costminimization analysis was performed. On the other hand, For populations to which
FF/UMEC/VI have additional benefit, cost-effectiveness analysis was performed.

・ Parameters of Patients’ background inputted to the Galaxy COPD model should be
calculated from the data of Japanese population, not ITT population.
・ Based on the estimation by the Galaxy COPD model, the mortality between two
groups was different. However post-hoc analysis of the IMPACT trial suggested nodifference of the mortality. Model setting was changed so that the no difference ofmortality was observed.
The academic group re-calculated the results. The results were submitted tothe third session of the ECCEE and were approved. The final results obtained for each
population are provided hereafter.

Population

Prior

eosinophil

treatment

countABCDE<100/μLMITT(Triple
therapy bytwo doses)

F
G
H≥100/μL<100/μL≥100/μL<100/μL≥100/μL

ICS/LABA<100/μL≥100/μL

I

LAMA/LABA<100/μL

Jor LAMA≥100/μL

KL

LAMA<100/μL≥100/μL

Comparator
MITT (Triple
therapy bytwo doses)

Additional

ICER

benefit(JPY/QALY)

Not shown

Cost saving

Not shown

Cost saving“Unable to analyze”

ICS/LABA

LAMA/LABAICS/LABA

LAMA/LABAICS/LABA“Unable to analyze”
Not shown

Cost increasing

Not shown

Cost increasing

Yes

1,833,684

Yes

328,585

Not shown

Cost increasing

YesDominantYes

Dominant

Yes

483,056

USD 1 = JPY 105, and EUR 1=JPY 126 (as of March 2021)