Authors' objectives: The academic technology assessment group (ATAG) reviewed a report on molnupiravir's additional benefits and cost-effectiveness compared to standard of care (SoC) in adults with coronavirus disease 2019 (COVID-19) who are at an increased risk of progression to severe COVID-19 (except adults with severe COVID-19). The report was submitted by the manufacturer of molnupiravir (MSD). This report summarizes the results of a review and reanalysis conducted by the ATAG. When evaluating the additional benefits of molnupiravir over the SoC, the manufacturer provided data from the MOVe-OUT trial. The manufacturer insisted on the additional benefits of molnupiravir over SoC based on the MOVe-OUT trialfs findings, which indicated that molnupiravir had a statistically significant effect on the incidence of hospitalization or death at day 29 compared with placebo. The ATAG observed that the MOVe-OUT trial was conducted in unvaccinated adults infected with the delta, gamma, and mu variants of SARS-CoV-2. Given that the main variant of SARS-CoV-2 is Omicron and COVID-19 vaccination has become widespread in Japan, the generalizability of the study results is limited. Therefore, the ATAG proposed that the evaluation should follow the PANORAMIC trial (conducted in the U.K., University of Oxford) for vaccinated adults infected with omicron variants. However, owing to differences in the definition of risk factors for progression to severe COVID-19 and the SoC in Japan versus the U.K., the PANORAMIC trial included participants who were not defined as having risk factors in Japan and those who were treated with other medications indicated for the treatment of COVID-19. Therefore, the ATAG evaluated the treatment effect of molnupiravir after extracting adults who met the Japanese definition of risk factors for progression to severe COVID-19 and the SoC in Japan from the PANORAMIC study. The post-hoc analysis of the PANORAMIC trial demonstrated that the odds ratio for hospitalization or death was 1.053 (95% confidence interval: 0.775?1.396), and the difference in event rate was not significant between the molnupiravir plus usual care group and the usual care group. Based on these results, the ATAG 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 based on the results of the subgroup analysis by age; however, the available evidence is limited, and further data are required to establish these benefits. The manufacturer conducted a cost-effectiveness analysis using a decision-tree model representing the acute phase of COVID-19 and a Markov model representing the post-acute phase of COVID-19. As molnupiravir did not exhibit additional benefits over the SoC, the ATAG conducted a cost-minimization analysis, revealing that molnupiravir increased costs by JPY 94,312. In conclusion, for adults with COVID-19 at an increased risk of progression to severe COVID-19, the results of the ATAG analysis suggest that the ICER for molnupiravir compared with SoC is likely to indicate equivalent effectiveness and cost increase from the perspective of public healthcare payers in Japan.

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2024

URL for published report: https://c2h.niph.go.jp/en/results/C2H2208.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com