OBJECTIVE: The COVID-19 pandemic remains a large burden on the US healthcare system. Novel oral antivirals, molnupiravir and PF-07321332/ritonavir, have been shown to prevent both hospitalization and death in high-risk adults (defined as unvaccinated patients with at least one risk factor for progression to severe COVID-19). The objective of this analysis is to determine a threshold price for cost-effective use of molnupiravir and PF-07321332/ritonavir in the prevention of severe COVID-19 in high-risk US adults.

METHODS: We developed a decision analysis tree to analyze treatment with molnupiravir, PF-07321332/ritonavir, or placebo to prevent severe COVID-19 as measured by hospitalization and death in patients with laboratory-confirmed COVID-19. Key assumptions included all deaths were COVID-19 related and all patients were hospitalized before death. We used a US payer perspective and a lifetime time horizon. QALYs lost due to COVID-19 death were extracted from the literature and accounted for comorbidities, age, and discounting. Costs were obtained from literature and manufacturer-reported US-government price agreements of $710 and $529 per treatment course for molnupiravir and PF-07321332/ritonavir, respectively. Parameter uncertainty was assessed with a deterministic one-way sensitivity analysis (OWSA).

RESULTS: Given a willingness-to-pay threshold of $100,000/QALY, estimated threshold prices per treatment course were $1,287 for molnupiravir and $2,643 for PF-07321332/ritonavir. PF-07321332/ritonavir appears to dominate both placebo and molnupiravir. PF-07321332/ritonavir dominated placebo across all parameter ranges in the OWSA except an increase in PF-07321332/ritonavir hospitalization rate.

CONCLUSION: PF-07321332/ritonavir appears to dominate placebo and molnupiravir for the prevention of severe COVID-19 in unvaccinated high-risk adults. Cost-effective use is estimated at $2,643 per PF-07321332/ritonavir treatment course at a threshold of $100,000/QALY. The gap between this estimated threshold price and current negotiated price agreements highlights the public health importance of affordability of these antivirals. More evidence is needed to determine if these agents will be useful in vaccinated high-risk US adults.