Authors' objectives: The academic technology assessment group (ATAG) reviewed a report on nirmatrelvir/ritonavir's additional benefits and cost-effectiveness in patients with COVID-19 (Pfizer Japan Inc.). This report summarizes the results of the review and the re-analysis by the ATAG. The target population was adult COVID-19 patients with risk factors toward severe COVID-19. The situation in Japan was considered in the analysis scope since the emergence of the Omicron variant, as well as vaccination coverage. In evaluating the additional benefits of nirmatrelvir/ritonavir, the manufacturer noted that no randomized controlled trials (RCT) that directly compared nirmatrelvir/ritonavir and molnupiravir were identified. Given this, the manufacturer identified the EPIC-HR trial, a clinical trial evaluating nirmatrelvir/ritonavir, following a systematic review. The manufacturer conducted a matching-adjusted indirect comparison with the MOVe-OUT trial, a clinical trial evaluating molnupiravir (the comparator drug). The manufacturer found the effectiveness of nirmatrelvir/ritonavir in preventing severe disease (hospitalization or death due to COVID-19) and concluded that nirmatrelvir/ritonavir offers added benefit over molnupiravir. The ATAG pointed out that both the EPIC-HR and MOVe-OUT trials did not match the analysis scope, where the Omicron variant was prevalent and COVID-19 vaccination had become widespread. Furthermore, the EPIC-SR trial, published after the manufacturer's analysis, failed to demonstrate efficacy in shortening the duration of symptoms compared with placebo, while nirmatrelvir/ritonavir had fewer hospitalizations or deaths in 28 days although the result was not statistically significant. Although the result indicates potential benefit, EPIC-SR was conducted when Delta variant was prevalent and its sample size was not sufficient to assess the efficacy in preventing severe disease. Therefore, the ATAG concluded that it was difficult to provide a definitive assessment of the additional benefits based on the available evidence as of May 2024 and recommended that the assessment be based on PANORAMIC trial. The trial is a platform-adaptive RCT involving three groups-nirmatrelvir/ritonavir, molnupiravir and placebo-, and was conducted in the United Kingdom amidst the ongoing vaccination program and the Omicron variant spread; it was therefore considered appropriate to assess the additional benefit of nirmatrelvir/ritonavir based on the results of this trial. The patient enrolment had already been completed by May 2024. The Central Social Insurance Medical Council determined to suspend the evaluation for one year in September 2024 and restart it in November 2025, with the 3-month additional analysis period. However, no additional literature supporting additional benefit was identified, including the available evidence from PANORAMIC trial. The ATAG therefore concluded that nirmatrelvir/ritonavir did not demonstrate additional benefit compared with the comparator technology. The manufacturer conducted a cost-effectiveness analysis using a decision tree model for the acute period from the onset of COVID-19 to the end of acute treatment, and a Markov model for the subsequent lifetime analysis period. Parameters from an indirect comparison of the EPIC-HR and MOVe-OUT trials were used for the model's effectiveness in preventing severe disease. The ATAG evaluated that nirmatrelvir/ritonavir did not offer additional benefit compared to molnupiravir, and then the ATAG conducted a cost-minimization analysis. As a result, the cost of the nirmatrelvir/ritonavir group was 12,432 yen higher than that of the molnupiravir. Based on the result of the analysis, the ATAG suggest that nirmatrelvir/ritonavir is likely to fall into the category of "equivalent (or inferior) effectiveness and increased costs" when compared with molnupiravir.

Project Status: Completed

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

Year Published: 2026

URL for published report: https://c2h.niph.go.jp/en/results/C2H2211.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