Cost-Effectiveness of Ensitrelvir for COVID-19 Post-Exposure Prophylaxis Among High-Risk Household Contacts in Japan: A Model-Based Cost-Utility Analysis

Background

Ensitrelvir reduced symptomatic COVID-19 after household exposure in the SCORPIO-PEP trial, but its economic value as post-exposure prophylaxis is unknown.

Objective

To estimate the cost-effectiveness of ensitrelvir post-exposure prophylaxis for high-risk household contacts in Japan.

Methods

We developed a decision-analytic cost-utility model from the Japanese public healthcare payer perspective. Trial risks of symptomatic COVID-19 through day 10 were linked to Japanese evidence on hospitalization, mortality, costs, quality of life, and life expectancy. Because the trial observed no COVID-19-related hospitalization or death, downstream outcomes were modeled only through prevention of symptomatic disease. We performed deterministic, probabilistic, structural, subgroup, and threshold analyses.

Results

Ensitrelvir increased costs by JPY 54,945 and gained 0.003267 QALYs per exposed contact, yielding an ICER of JPY 16.82 million/QALY. None of 10,000 simulations was cost-effective at JPY 5 million/QALY. Applying the overall-trial relative risk to the high-risk baseline yielded JPY 19.24 million/QALY. Restricting post-acute utility loss to 6 months, halving it, or excluding it yielded ICERs of JPY 23.62 million, JPY 26.76 million, and JPY 65.51 million/QALY, respectively. The drug acquisition-cost threshold was JPY 11,021 per course.

Conclusions

At current Japanese costs, ensitrelvir post-exposure prophylaxis for high-risk household contacts was unlikely to be cost-effective at JPY 5 million/QALY. This conclusion remained unfavorable under conservative efficacy, post-acute utility, hospitalization-attribution, and mortality assumptions. Severe-outcome benefits remain model-based extrapolations rather than trial-observed effects.

Key Points for Decision Makers

• The pivotal post-exposure prophylaxis trial showed a substantial reduction in symptomatic COVID-19, but no COVID-19-related hospitalization or death occurred; modeled severe-outcome benefits therefore depend on external Japanese evidence.

• At current Japanese drug and delivery costs, the base-case ICER was JPY 16.82 million per QALY. The probability of cost-effectiveness was 0% at JPY 5 million per QALY and 2.28% at JPY 10 million per QALY.

• The acquisition-cost threshold was approximately JPY 11,000 per course. Conservative efficacy and post-acute utility scenarios remained above JPY 19 million and JPY 23 million per QALY, respectively.