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A single pill of the study drug molnupiravir, taken twice daily for 5 days, eliminated SARS-CoV-2 from the nasopharynx of 49 participants.
That prompted Carlos del Rio, MD, a senior professor of medicine at Emory University in Atlanta, Georgia, to envision a future where a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe prevent disease, similar to Tamiflu for flu. .
“I think it’s critical,” he said Medscape Medical News of the data. Emory University was involved in the molnupiravir trial, but del Rio was not part of that team. “This drug provides the first antiviral oral drug that can then be used in an outpatient setting.”
Still, Del Rio said it’s too early to call this particular drug the breakthrough clinicians need to keep people out of IC.
“It has the potential be practice-changing; it does not change 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 have to see if people get better from an actual disease” to assess the drug’s true value in clinical care.
“That’s a phase 3 goal we have to prove,” she told Medscape Medical News.
Phase 2/3 studies of the drug’s efficacy and safety are now underway in hospitalized and non-hospitalized patients.
In a short, pre-recorded presentation of the data, Painter explained what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing a catastrophic viral error – essentially overloading the virus with replication and mutation until the virus burns itself up and cannot produce replicable copies.
In this phase 2a, randomized, double-blind control study, researchers recruited 202 adults treated in an outpatient setting with fever or other symptoms of a respiratory virus and a confirmed SARS-CoV-2 infection on Day 4. Participants were randomly assigned to three different groups: 200 mg molnupiravir, 400 mg; or 800 mg. The 200 mg arm was paired one-to-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 were then followed for a total of 28 days to check for complications or side effects. On days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for PCR tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus present can infect others as well. .
Notably, the pills do not need to be refrigerated at any point in the process, easing the cold chain challenges that vaccines have plagued with.
“There is an urgent need for an easy to manufacture, transport, store, and administer SARS-CoV-2 antiviral agent,” Painter said.
Of the 202 people who were recruited, 182 had smears that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.
On Day 3, 28% of patients in the placebo group had SARS-CoV-2 in their nasopharynx, compared to 20.4% of patients who received a 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 the people in the placebo group still had a detectable virus.
There were already differences in the presence of infectious virus halfway through the treatment. On day 3 of the 5-day course, 36.4% of the participants in the 200 mg group had detectable virus in the nasopharynx, compared to 21% in the 400 mg group and only 12.5% in the 800 mg group. group. And while the decrease in SARS-CoV-2 was noticeable in the 200 mg and 400 mg arm, it was only statistically significant in the 800 mg arm.
In contrast, by 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 of the disease course of SARS-CoV-2.
“You just don’t know” which infections will lead to serious illness, Painter said Medscape Medical News“And wouldn’t you want us to?”
Seven participants discontinued treatment, although only four experienced side effects. Three of them stopped the study because of side effects. The study is still blinded, so it’s unclear what those events were, but Painter said they weren’t thought to be related to the study drug.
The bottom line, Painter said, was that people treated with molnupiravir had vastly different results in laboratory measurements during the study.
“An average of 10 days after the onset of symptoms, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there was not only a virus in the nasopharynx, but it was able to replicate, Painter said. “In contrast, none of the molnupiravir-treated patients could be recovered on Study Day 5.”
Conference on Retroviruses and Opportunistic Infections 2021: Abstract SS777. Presented March 6, 2021.
Heather Boerner is a scientific and medical reporter based in Pittsburgh, PA and can be found on Twitter at @HeatherBoerner. Her book Positively Negative: Love, Sex, and Science’s Surprising Victory Over HIV was released in 2014.
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