— Independent appraisal committee votes 11-2 that the evidence is not adequate to demonstrate a net health benefit for molnupiravir over symptomatic care alone; Paxlovid and fluvoxamine receive more favorable votes —

— Through government price negotiation or generic pricing, economic modeling suggests all three treatments have prices well aligned with patient benefits, with all drugs also conveying important other potential benefits beyond direct health improvement —

— Policy recommendations include a focus on transition to private market payment for these treatments, at which point manufacturers and payers should explore innovative reimbursement approaches such as subscription-based models or volume-based purchasing models in order to avoid restrictions on access through tight utilization management —

BOSTON, May 10, 2022 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of the following outpatient treatments for COVID-19:

  • molnupiravir (Merck)
  • PF-07321332/ritonavir (Paxlovid™, Pfizer)
  • fluvoxamine (Investigator initiated)

Information on monoclonal antibody treatments sotrovimab and REGEN-COV2 is included in supplemental documents to the report given that, at the time of this final report, these treatments no longer had active emergency use authorization (EUA) from the Food and Drug Administration (FDA) for use in any U.S. region.

ICER’s report on outpatient COVID-19 therapies was reviewed at the April 2022 public meeting of the Midwest CEPAC (Midwest CEPAC), one of ICER’s three independent evidence appraisal committees.

Downloads: Final Evidence Report | Report-at-a-Glance | Policy Recommendations

“The evidence on outpatient treatments for COVID-19 must be viewed as highly sensitive to the evolving landscape of COVID-19 variants and vaccination status in the US,” said ICER President Steven Pearson, MD, MSc. “As indicated by the votes from the independent appraisal committee, the current evidence was judged more persuasive for Paxlovid and fluvoxamine than for molnupiravir, but clinical trials are ongoing for all three treatments.  At their current negotiated price (molnupiravir, and Paxlovid) or their generic market price (fluvoxamine), these drugs appear to have prices reasonably aligned with patient benefits. One of the key lessons to be learned from the development of these drugs is that the federal government’s advance market commitment mechanism was effective in reducing the financial uncertainty that could have deterred manufacturers from bringing a drug to market, and ultimately resulted in multiple drugs becoming available in a relatively short time at prices that were aligned with clinical benefit.  That experience has many lessons for the future of US policy in preparing for future pandemics.”

Voting on Clinical Effectiveness and Contextual Considerations

A majority (11-2) found current evidence is not adequate to demonstrate a net health benefit when molnupiravir is compared to symptomatic care alone.

All panelists (13-0) found that current evidence is adequate to demonstrate a net health benefit when Paxlovid is compared to symptomatic care alone.

A slight majority (7-6) found that current evidence is adequate to demonstrate a net health benefit when fluvoxamine is compared to symptomatic care alone.

During their deliberations, panel members also weighed the therapies’ other potential benefits, disadvantages, and contextual considerations. Discussion highlighted the following potential benefits of effective outpatient treatments for COVID-19 beyond those of health improvement for individual patients:

  • Effective outpatient treatments for mild-moderate COVID-19 may help reduce population spread of COVID-19.
  • Effective outpatient treatments for mild-moderate COVID-19 may reduce the number of hospitalized patients enough to increase capacity to treat non-COVID-19-related conditions.​
  • Effective outpatient treatments for mild-moderate COVID-19 will help address the disparate burden of the pandemic in disadvantaged communities.
  • Effective outpatient treatments for mild-moderate COVID-19 may help provide psychological reassurance allowing for broader opening of schools and workplaces.
  • Molnupiravir cannot be used in people who are attempting to conceive or who are pregnant.
  • Paxlovid has many drug-drug interactions that may limit the number of patients who can use it.
  • Fluvoxamine affects a different phase in COVID-19 pathophysiology and therefore it may be possible to combine its use with other agents.​

Voting on Long-Term Value for Money

After reviewing the clinical evidence and considering the treatments’ other potential benefits, disadvantages, and contextual considerations noted above, the Midwest CEPAC evaluated the long-term value for these treatments.  All three treatments had prices that fell below the level of ICER’s health benefit price benchmarks derived from cost-effectiveness modeling:

  • Due to uncertainty in the net health benefit for molnupiravir, a majority of panelists voted that it represents “low-to-intermediate” long-term value for money.
  • A majority of panelists found that Paxlovid represents “high” long-term value for money.
  • A majority of panelists found that fluvoxamine represents “intermediate-to-high” long-term value for money.

ICER’s HBPBs are price ranges suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

Key Policy Recommendations

ICER’s independent assessment of value informs the critical decisions that stakeholders across the US health system need to make around pricing and coverage. Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, representatives from US payers, and pharmaceutical manufacturers — convened to discuss the pricing implications and recommendations to ensure fair access. Key recommendations stemming from the roundtable discussion include:

  • Federal policymakers should view the advance market commitment strategy followed with outpatient COVID-19 treatments as a success that should be built upon. 
  • The framework for drug price negotiation between the government and drug makers during a pandemic should be made more transparent so that the public is aware of the parameters that the federal government considers in pricing negotiations.
  • The FDA needs to establish a clear and effective pathway for supporting evaluation of repurposed drugs during a pandemic.

  • The federal government should work with states and other policymakers to adopt policy changes needed to improve the effectiveness of its “test-to-treat” program. 

  • When COVID-19 drug pricing and payment moves from federal contracts into private markets, manufacturers and payers should work together to explore innovative approaches for coverage and pricing that minimize the use of restrictive coverage access as a means of cost control.

ICER’s full set of policy recommendations, including comprehensive considerations for establishing evidence-based prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.