{"id":10609,"date":"2023-01-17T11:48:24","date_gmt":"2023-01-17T16:48:24","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=10609"},"modified":"2023-01-18T20:21:40","modified_gmt":"2023-01-19T01:21:40","slug":"after-the-panoramic-study-whither-molnupiravir","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/after-the-panoramic-study-whither-molnupiravir\/2023\/01\/17\/","title":{"rendered":"After the PANORAMIC Study — Whither Molnupiravir?"},"content":{"rendered":"
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Photo by Piret Ilver<\/a> on Unsplash<\/a>.<\/p><\/div>\n

We turn now to the second of the controversial papers published in late 2022 on COVID-19 — namely the PANORAMIC study of molnupiravir versus usual care in outpatients with the disease<\/a>. This one is controversial not because the study was poorly done, or unimportant, but because molnupiravir has, from the start, been a contentious treatment for this disease.<\/p>\n

Conducted in the United Kingdom, PANORAMIC was impressively large, enrolling over 25,000 people. Eligible participants had symptoms for 5 days or fewer, and were either older than 50 or had comorbidities known to increase the severity of the disease. Randomization was to open-label molnupiravir or usual care. The primary endpoint was hospitalization or death. Importantly, 94% of the participants had already received three doses of a COVID-19 vaccine.<\/p>\n

The main study results were negative — hospitalization or death occurred in only 1% of participants in both groups. Serious adverse events were evenly matched between arms.<\/p>\n

On the plus side, people assigned to receive molnupiravir had a substantially faster time to recovery, 9 vs. 15 days, which yielded a >99% chance of the molnupiravir being superior to usual care for this protocol-specified endpoint. Active treatment also decreased healthcare utilization, and reduced viral load compared to usual care.<\/p>\n

The critical view of molnupiravir:<\/strong>\u00a0 Great study in a highly relevant population — those who are not just “fully vaccinated,” but also boosted. In this context, molnupiravir did nothing to reduce the serious outcomes of hospitalization or death.<\/p>\n

And ignore those time to recovery results. It’s an open-label study, with people getting active treatment of course thinking that what they’re getting is working. The placebo effect in treatment trials can be massive.<\/em><\/p>\n

Only this isn’t a harmless placebo — it’s an antiviral with a concerning mechanism of action, inhibiting viral replication by increasing the frequency of viral RNA mutations. Such a process could conceivably spawn more contagious or more immune evasive SARS-CoV-2 variants, something we definitely want to avoid.<\/p>\n

Plus, there’s the ongoing concern about mutagenesis, which has implications for those of reproductive age, and might have other long-term safety issues.<\/p>\n

Finally, molnupiravir isn’t cheap. Don’t be fooled that it’s “free”, or covered by insurance, or government programs. It’s $700 for a five-day course, another disadvantage it has compared to placebo.<\/p>\n

Now that we know this giant, well-done study is negative, can we take molnupiravir off the treatment guidelines completely, please? Or consider withdrawing the Emergency Use Authorization?<\/p>\n

For further concise, and (mostly) critical thoughts, read the responses to this post:<\/p>\n

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pic.twitter.com\/5mx7i0Yy7y<\/a><\/p>\n

— Patrick Kenney (@PatrickKenney7) January 13, 2023<\/a><\/p><\/blockquote>\n