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

March 13, 2024

[C2H2208] Summary of cost-effectiveness evaluationof molnupiravir (Lagevrio®)
1. Indications
Coronavirus disease 2019 (COVID-19)
2. Price of the drug
Molnupiravir has been reimbursed from August 2022 at JPY 2,357.80 (as of March2024). The price was calculated using a cost calculation method with a usefulness
premium (II) of 10%. This product was designated as an H1 cost-effectivenessevaluation item.
3. Scope of cost–effectiveness evaluation
This product is indicated for the treatment of COVID-19. The scope of evaluationagreed upon at the first session of the Expert Committee of Cost-EffectivenessEvaluation (ECCEE) is described below.
Adults with COVID-19 who have an increased risk ofprogression to severe COVID-19 (aged 18 years and older)
Population(except adults with severe COVID-19*)*The definition follows Clinical Management of Patients with
COVID-19 by the MHLW version 8.1
Standard of care (SoC)*Comparator* Except other medications indicated for treatment of COVID19

4. Evaluation of additional benefits
The manufacturer performed a systematic review of randomized controlled trials(RCTs). Of these, they used the MOVe-OUT trial to evaluate additional benefits.

The manufacturer insisted on the additional benefits of molnupiravir over SoC
because the MOVe-OUT trial showed that molnupiravir had statistically significant
effect on the incidence of hospitalization or death at day 29 compared to placebo(molnupiravir: 7.3%, placebo: 14.1%, difference: -6.8%(95% CI：-11.3 to -2.4)).
The academic group noted that the MOVe-OUT trial was conducted in
unvaccinated adults infected with the delta, gamma, and mu variants of SARSCoV-2. Because the main variant of SARS-CoV-2 is Omicron and COVID-19
vaccination has become widespread in Japan, the generalizability of the study
results to Japanese clinical practice is limited. Therefore, the academic groupconsidered that the evaluation should be conducted according to the PANORAMIC
trial (U.K., University of Oxford) for vaccinated adults infected with omicronvariants. However, due to differences in the definition of risk factors for
progression to severe COVID-19 and the SoC in Japan and the U.K., thePANORAMIC trial included some participants who were not necessarily defined ashaving risk factors in Japan and those who were treated with other medications
indicated for COVID-19 when using molnupiravir. Therefore, the academic group
evaluated the treatment effect of molnupiravir after extracting adults who met
the Japanese definition of risk factors for progression to severe COVID-19 andthe SoC in Japan from the PANORAMIC study. The post-hoc analysis of thePANORAMIC trial demonstrated that the odds ratio for hospitalization or death
was 1.053 (95% CI: 0.775 to 1.396), and the difference in event rate was not
significant between the molnupiravir plus usual care group and the usual caregroup. Thus, the academic group could not determine that molnupiravir had
additional benefits for hospitalization or death. Clinical experts have suggested
that molnupiravir may have additional benefits for older adults from subgroup
analysis by age; however, the available evidence is limited, and further data arerequired to establish their benefits.
5. Results of the cost-effectiveness analysis
The manufacturer performed a cost-effectiveness analysis using a decision-tree
model expressing the acute phase of COVID-19 and a Markov model expressing
the post-acute phase of COVID-19. The academic group performed a costminimization analysis because molnupiravir did not show any additional benefits
over the SoC. The ECCEE accepted the following results:

Population

Comparator

Additional
benefit

ICER (JPY/QALY)

Adults with COVID-19 whohave an increased risk ofprogression to severe
COVID-19SoC

No additional
benefitCost increase