PANORAMIC RCT – Molnupiravir…or Mol-NOPE-iravir?

February 8, 2023

Written by Jason Lesnick

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Molnupiravir does not decrease death or hospitalization in vaccinated patients with COVID-19 at high risk for progression to severe disease.

Why does this matter?
Molnupiravir is an antiviral drug developed initially to treat the flu but then repurposed in an attempt to provide oral therapy against COVID-19. An industry funded, placebo controlled phase 3 trial in unvaccinated non-hospitalized patients with COVID-19 at high risk of adverse outcomes showed a 30% reduction in hospital admissions and deaths. Would this oral treatment show benefit in vaccinated adults at high risk for deterioration from COVID-19 when omicron was the dominant variant? 

More like mol-nope-iravir, am I right?
From December 8th, 2021 until April 27th, 2022 patients were recruited and randomly assigned to receive 800 mg molnupiravir BID for 5 days plus usual care or usual care only. The patient population of 25,783 participants included people ≥ 50 years old or > 18 years with relevant comorbidities and confirmed COVID-19 for ≤ 5 days. 94% of participants had at least 3 doses of a SARS-CoV-2 vaccine. 

The authors used a Bayesian logistic regression model. Hospitalization or death was recorded in 105 of 12,529 (0.8%) patients in molnupiravir group compared to 98 of 12,525 (0.8%) in the usual care group, aOR1.06 (95% Bayesian credible interval, BCI 0.81-1.41). There was no evidence of a treatment interaction in any of the analyzed subgroups. Those who received molnupiravir showed earlier recovery with regard to symptom improvement – 9 days compared to 15 days in the usual care group, estimated benefit 4.2 days (95%BCI 3.8-4.6). 

The primary analysis estimated a 33% chance of superiority (reducing hospitalization or death with addition of molnupiravir to usual care) but also that there is a 67% chance of inferiority (that molnupiravir could increase hospitalization or death). 

This well done study reaffirms my practice of not prescribing molnupiravir for the vast majority of COVID-19 patients. 

Editor’s note: I agree with Jason, as do NIH treatment guidelines. Molnupiravir should not be a first-line drug. I have largely used it in immunocompromised patients who have drug-drug interactions with nirmatrelvir/ritonavir (Paxlovid). Avoid it during pregnancy. ~Clay Smith

Source
Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet (London, England) vol. 401,10373 (2023): 281-293. doi:10.1016/S0140-6736(22)02597-1.