ICER Says No to Molnupiravir, Yes to Paxlovid and Fluvoxamine for Outpatient COVID Treatment

Merck’s oral COVID treatment molnupiravir lacks adequate evidence to support claims that it’s any more effective than symptomatic care.

That was the verdict from the Institute for Clinical and Economic Review (ICER), which recommended two out of three outpatient treatments for COVID-19 now on the market — Pfizer’s Paxlovid (nirmatrelvir and ritonavir) and the generic antidepressant fluvoxamine — but said molnupiravir is a no go.

Eleven of the 13 members of the influential independent nonprofit research panel said that current data on molnupiravir’s superiority to symptomatic care alone is insufficient. At the same time, all 13 said evidence on Paxlovid is enough to establish a net health benefit, and seven out of 13 found fluvoxamine to be sufficiently supported by evidence.

But those recommendations could change as clinical trials are ongoing for all three treatments, said ICER’s President Steven Pearson.

“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 U.S.,” Pearson said.

As for pricing, all three are affordable, ICER said.

“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,” wrote ICER.

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. And a majority of panelists found that fluvoxamine represents “intermediate-to-high” long-term value for money.

The FDA granted Emergency Use Authorization (EUA) for molnupiravir (branded as Lagevrio) in December of 2021 for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19 and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. A month prior, the drug received approval in the UK.

Paxlovid was also granted EUA by the FDA in December of 2021 for the treatment of mild-to-moderate COVID-19 in adults and children (age 12 years and older weighing at least 40 kg) who are also at high risk for progression to severe COVID-19.

Fluvoxamine (branded as Luvox) has been on the market since 1994 to treat obsessive-compulsive disorder and depression. Still, in a clinical trial, those taking the selective serotonin reuptake inhibitor (SSRI) and a sigma-1 receptor (S1R) agonist had far fewer hospitalizations that those on placebo. The fluvoxamine arm of the trial was stopped due to superiority.

Said ICER, 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.”

Other factors the ICER panel took into consideration about the drugs included that molnupiravir cannot be used in people who are attempting to conceive or who are pregnant and that Paxlovid has many drug-drug interactions that may limit the number of patients who can use it. Also, fluvoxamine affects a different phase in COVID-19 pathophysiology and therefore it may be possible to combine its use with other agents, ICER said.

The institute said that 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.

ICER said that federal policymakers should view the advance market commitment strategy followed with outpatient COVID-19 treatments as a success that should be built upon. “That experience has many lessons for the future of U.S. policy in preparing for future pandemics,” said ICER.

“The framework for drug price negotiation between the government and drugmakers 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,” ICER wrote, adding that the FDA needs to establish a clear and effective pathway for supporting evaluation of repurposed drugs during a pandemic.

Merck did not respond to a request for comment.

Read the ICER analysis here: www.fdanews.com/05-13-22-ICERCOVID19FinalEvidenceReport.pdf. — Suz Redfearn