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A single pill of the experimental drug molnupiravir, taken twice daily for 5 days, cleared SARS-CoV-2 from the nasopharynx of 49 participants.
This prompted Carlos del Rio, MD, distinguished professor of medicine at Emory University in Atlanta, Georgia, to suggest a future in which a drug such as molnupiravir could be taken in the early days of symptoms to prevent serious illnesses, similar to Tamiflu for influenza.
“I think it is extremely important,” he said Medscape Medical News of the data. Emory University was involved in testing molnupiravir, but del Rio was not part of that team. “This medication offers the first oral antiviral medication that could be used on an outpatient basis.”
Still, del Rio said it is too early to call this specific medication that doctors need to keep people out of the ICU.
“Has the potential be a change in practice; it is not a change in practice at the moment. “
Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the virtual Conference on Retroviruses and Opportunistic Infections, agreed. While the data is promising, “we will need to see if people get better with real illnesses” to assess the drug’s real value in clinical treatment.
“This is a phase 3 objective that we need to prove,” she told Medscape Medical News.
Phase 2/3 drug efficacy and safety studies are ongoing in hospitalized and outpatients.
In a brief pre-recorded presentation of the data, Painter exposed what the researchers know so far: preclinical studies suggest that molnupiravir is effective against several viruses, including coronavirus and specifically SARS-CoV-2. It prevents a virus from replicating itself by inducing a catastrophe of viral error – essentially overloading the virus with replication and mutation until the virus burns and cannot produce replicable copies.
In this phase 2a, double-blind, randomized control trial, the researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection on day 4. Participants were randomly assigned to three different groups: molnupiravir 200 mg, 400 mg; or 800 mg. The 200 mg arm was combined one by one with a placebo-controlled group, and the other two groups had three participants in the active group for each control.
Participants took the pills twice a day for 5 days and then were followed up for a total of 28 days to monitor for complications or adverse events. On days 3, 5, 7, 14 and 28, the researchers also collected nasopharyngeal smears for PCR testing, to sequence the virus and to grow cultures of SARS-CoV-2 to see if the virus that is present is really capable of infecting other people.
Notably, the pills do not need to be refrigerated at any point in the process, alleviating the cold chain challenges that have affected vaccines.
“There is an urgent need for an antiviral drug that is easily produced, transported, stored and administered against SARS-CoV-2,” said Painter.
Of the 202 people recruited, 182 had smears that could be evaluated, of which 78 had infection at the beginning of the study. The results are based on the laboratories of these 78 participants.
On day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients who received any dose of molnupiravir. But on day 5, none of the participants who received the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable viruses.
Halfway through the treatment, the differences in the presence of infectious viruses were already evident. On day 3 of the 5-day course, 36.4% of participants in the 200 mg group had detectable viruses in the nasopharynx, compared with 21% in the 400 mg group and only 12.5% in the 800 mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200 mg and 400 mg arms, it was only statistically significant in the 800 mg arm.
In contrast, at the end of the 5 days in the placebo groups, the infectious virus ranged from 18.2% in the 200 mg placebo group to 30% in the 800 mg group. This points to the variability in the course of SARS-CoV-2 disease.
“You just don’t know” which infections will lead to serious illness, said Painter Medscape Medical News. “And wouldn’t you like us to do it?”
Seven participants discontinued treatment, although only four experienced adverse events. Three of them discontinued the study due to adverse events. The study is still blind, so it is unclear what those events were, but Painter said they were unrelated to the study drug.
The end result, Painter said, was that people treated with molnupiravir had totally different results in laboratory measurements during the study.
“On average 10 days after the onset of symptoms, 24% of the placebo patients remained culture positive” for SARS-CoV-2 – meaning that there was not only a virus in the nasopharynx, but was able to replicate, Painter said. “In contrast, no infectious virus could be recovered on day 5 of the study in any patient treated with molnupiravir.”
Conference on Retroviruses and Opportunistic Infections 2021: Abstract SS777. Presented on March 6, 2021.
Heather Boerner is a medical and scientific reporter based in Pittsburgh, PA and can be found on Twitter at @HeatherBoerner. His book, Positively Negative: Love, Sex, and Science’s Surprising Victory Over HIV, was released in 2014.
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