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:http://c2h.niph.go.jp

April 21, 2021

[C2H1903] Summary of cost-effectiveness evaluationof Ravulizumab (Ultomiris)
1. Indications
Paroxysmal nocturnal hemoglobinuria (PNH)
2. Drug price
Ravulizumab was reimbursed in September 2019 for JPY 730,894 (as of April 2021).
The price was calculated using the similar efficacy comparison method, with ausefulness premium of 5%. This product is designated as an H1 cost-effectivenessevaluation item.
3. Scope of cost-effectiveness evaluation
Ravulizumab has indication for PNH. Standard therapy, eculizumab (Soliris), needs
to be administered every 2 weeks, but ravulizumab is administered every 8 weeks.
The scope of evaluation agreed upon at the first session of the Expert Committee of
Cost-Effectiveness Evaluation (ECCEE) is described hereafter. Eculizumab, which isthe current standard therapy, was used as a comparator. On the contrary, best
supportive care (BSC) could be a comparator for patients who were potentiallytargeted to eculizumab but did not receive it. However, the number of such patients
is limited and it is possible that the results of the analysis have large uncertainties.
Therefore, eculizumab was used as a comparator for the sensitivity analysis.

Population

Paroxysmal nocturnal hemoglobinuria (PNH)
EculizumabComparator

In addition, analysis of best supportive care (BSC) used as thecomparator is performed as a sensitivity analysis.

4. Evaluation of additional benefits
Based on the systematic review, two randomized control trials (RCTs), the 301 and302 trials, corresponding to the research questions were detected. In the 301 trial,patients with PNH treated with a complement inhibitor were selected. In contrast, the302 trials included patients with PNH who received eculizumab for more than 6months.
The manufacturer insisted that ravulizumab has an additional benefit to eculizumab
in terms of “reduction of free C5-related breakthrough hemolysis (BTH),” ”avoidanceof blood transfusion,” and “improvement in quality of life (QOL) because frequencyof injection is reduced.”【Free C5-related BTH】
･ According to the 301 and 302 trials, the incidence rate of free C5-related BTH wasnot significantly different between the groups.
･ As the measurement of free C5 is not commonly used in clinical practice, theappropriateness of the endpoint was not clear.
･ The dose of ravulizumab is determined based on the patient’s weight. In contrast,
eculizumab dosage is fixed regardless of the patient’s body weight. Therefore, it ispossible that the dose of eculizumab for patients with a high body weight wasinadequate, thereby causing free C5-related BTH.
Avoidance of blood transfusions
According to the 301 and 302 trials, avoidance of blood transfusion was not
significantly different between the groups.
【Improvement in QOL because the frequency of injections is reduced】･ The discrete choice experiment (DCE) was used to investigate preference in general
people and not in patients. Such results cannot be used for the evaluation ofadditional benefits.
The academic group concluded that ravulizumab did not have an additional
benefit to eculizumab. The third session of the ECCEE accepted the academic group’sview.
5. Result of cost-effectiveness analysisThe manufacturer performed a cost-effectiveness analysis. However, as the additional
benefit was not proven, the academic group performed a cost-minimization analysis.
The comparative costing for 8 weeks showed that the cost of ravulizumab treatment
was higher than that of eculizumab by JPY 343,163.

When BSC was used as a comparator, the academic group accepted theresults submitted by the manufacturer, although the manufacture’s submission had
some problems.
Comparator

ICER (JPY/QALY)

eculizumab

Cost increase

BSC

101,700,385