国立保健医療科学院 保健医療経済評価研究センター
Center for Outcomes Research and Economic
Evaluation for Health (C2H), National Institute of
Public Health (NIPH) | URL:https://c2h.niph.go.jp

June 12, 2024

[C2H2210] Summary of cost-effectiveness evaluationof Tezepelumab (TezspireⓇ)
1. Indication
Severe or refractory asthma in whom symptoms cannot be controlled withexisting treatments
2. Price of the drug
Tezepelumab has been reimbursed since November 2022 at JPY 176,253 forsyringe formulation and 178,182 for pen formulation (as of June 2024). The
prices are calculated based on the similar efficacy comparison method, with ausefulness premium of 5%. This product is designated as an H1 costeffectiveness evaluation item.
3. Scope of cost-effectiveness evaluation
The scope of evaluation agreed upon at the first session of the Expert Committeeof Cost-Effectiveness Evaluation (ECCEE) is described below. This product is used
to treat severe or refractory asthma in whom symptoms cannot be controlledwith existing treatments with no phenotype or biomarker limitations. Dupilumab
was selected for the comparator in population (a-1).
Severe or refractory asthma in whom symptoms cannot be
controlled with existing treatments
Population(a) Type 2 asthma (eosinophil counts [EOS]≥150/μL or IgE
sensitization positive)(a-1) Type 2 asthma (EOS≥150/μL and IgE sensitizationnegative)

(a-2) Type 2 asthma (IgE sensitization positive)(b) Non-type 2 asthma (EOS<150/μL and IgE sensitization
negative)(a-1) Existing biologics (mepolizumab, benralizumab, anddupilumab) with the lowest priceComparator(a-2) Omalizumab(b) Standard of Care (SoC)**including beta-agonists and steroids

4. Evaluation of additional benefits
The manufacturer performed a systematic review for studies regarding
tezepelumab and comparators in each population. Although no randomized
controlled trials (RCTs) comparing tezepelumab and other biologics wereidentified, four RCTs comparing tezepelumab and placebo were identified. One ofthem was the NAVIGATOR trial, which is the Phase III trial for tezepelumab. Three
network meta-analysis (NMA) comparing biologics indirectly were also identified.
The manufacturer sorted the studies while considering the definition of eachpopulation and evaluated the additional benefits of tezepelumab based on annual
asthma exacerbation rate (AAER). The results were as follows: population (a-1)
the additional benefits were not proven because no studies meeting the definitionof this population were identified: (a-2) the additional benefits were provenbecause a NMA, which was performed based on the way similar to the identified
NMA by Menzies-Gow, et al., showed a superior tendency of tezepelumab (AAER
ratio against omalizumab, 0.61 [95% credible interval: 0.24 to 1.16]; and (b)the additional benefits were proven based on the result of re-analyzing theNAVIGATOR trial while considering the definition of this population. The academic
group judged that the results of the manufacturer’s evaluation were generally
acceptable, but the academic group referred data including a subgroup analysis
for patients at EOS≥150/μL in the NMA by Menzies-Gow, et al. to examine thevalidity of the conclusion for population (a-1). Based on the NMA by MenziesGow, et al., the AAER ratio against dupilumab 300 mg was 0.91 (95% credibleinterval: 0.58 to 1.44), and the point estimate was close to 1.0. Therefore, theacademic group judged that the additional benefits of tezepelumab were notproven in population (a-1) even when they referred the data which may beextrapolatable to this population. In addition, it should be noted that thedifferences in the effectiveness between biologics accompanied a large

uncertainty because the academic group recognized that the extent to thedifferences varied according to which indirect comparison methods were selectedon their review process.
5. Results of the cost-effectiveness analysis
The manufacturer performed a cost-effectiveness analysis using a Markov model
consisting of five health states, “well controlled”, “poor controlled”, “exacerbationfrom well control”, “exacerbation from poor control”, and “death”. The
manufacturer calibrated the transition probability to “death” to higher value
because the mortality rate calculated by the model was lower than 8.0%/2 years,
which was reported by an epidemiological study for patients with severe asthma
in France. However, the academic group removed the calibration because themortality rate from the French study was higher than that reported byepidemiological data in Japan and the inconsistency between the population inthe model and in the French study. The ECCEE accepted the following results.

Population(a-1) Type 2 asthma (EOS≥150/μ
L and IgE sensitization negative)(a-2) Type 2 asthma (IgEsensitization positive)

Comparator

Additionalbenefits

ICER (JPY/QALY)

Dupilumab

Not proven

Cost increase

Omalizumab

Proven41,602,810

Soc

Proven16,959,488(b) Non-type 2 asthma(EOS<150/μL and IgEsensitization negative)