By Brezo Boerner
A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.
That led Carlos del Rio, MD, distinguished professor of medicine at Emory University in Atlanta, Georgia, to suggest a future in which a drug like molnupiravir could be taken in the early days of symptoms to prevent severe illness, similar to Tamiflu for influenza.
“I think it’s vitally important,” he told Medscape Medical News regarding the data. Emory University participated in the molnupiravir trial, but del Rio was not part of that team. “This drug offers the first oral antiviral medication that could then be used in an outpatient setting.”
Even so, del Rio said it's too early to call this particular drug the breakthrough doctors need to keep people out of the ICU.
"It has the potential to change practice; it is not a change in practice at this time."
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 from an actual illness” to assess the true value of the drug in clinical care.
"That's a phase 3 endpoint that we'll have to demonstrate," he told Medscape Medical News.
Phase 2/3 efficacy and safety studies of the drug are currently being conducted in hospitalized and non-hospitalized patients.
In a brief, prerecorded presentation of the data, Painter outlined what researchers know so far: preclinical studies suggest that molnupiravir is effective against several viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing a viral error catastrophe , essentially overloading the virus with replication and mutation until it burns out and can no longer produce replicable copies.
In this phase 2a, randomized, double-blind, controlled trial , researchers recruited 202 adults who were treated in an outpatient clinic for 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 of molnupiravir, 400 mg, or 800 mg. The 200 mg arm was matched 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 daily for 5 days and were then monitored for a total of 28 days for complications or adverse events. On days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for PCR testing, sequencing the virus, and culturing SARS-CoV-2 to see if the virus present was actually capable of infecting others.
In particular, the pills do not need to be refrigerated at any point in the process, which alleviates the cold chain challenges that have plagued vaccines.
"There is an urgent need for an antiviral drug that can be easily produced, transported, stored, and administered against SARS-CoV-2," Painter said.
Of the 202 people recruited, 182 had swabs that could be tested, of which 78 showed infection at the start of the study. The results are based on the laboratory data of those 78 participants.
By day 3, 28% of patients in the placebo group had SARS-CoV-2 in their nasopharynx, compared to 20.4% of patients who received any dose of molnupiravir. But by 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 group still had detectable virus.
By the midpoint of the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200 mg group had detectable virus in their nasopharynx, compared to 21% in the 400 mg group and only 12.5% in the 800 mg group. And while the reduction in SARS-CoV-2 was notable in both the 200 mg and 400 mg arms, it was only statistically significant in the 800 mg arm.
Conversely, at the end of the 5-day period 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 highlights the variability in the course of SARS-CoV-2 disease.
"You just don't know" which infections will lead to serious illness, Painter told Medscape Medical News . "And wouldn't you want us to?"
Seven participants discontinued treatment, although only four experienced adverse events. Three of them stopped the trial due to adverse events. 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 conclusion, Painter said, was that people treated with molnupiravir had markedly different results in laboratory measurements during the study.
“On average, 10 days after symptom onset, 24% of placebo-treated patients remained culture-positive” for SARS-CoV-2, meaning that not only was the virus present in the nasopharynx, but it was capable of replicating, Painter said. “In contrast, no infectious virus could be recovered by day 5 of the study in any patient treated with molnupiravir.”
Conference on Retroviruses and Opportunistic Infections 2021: Summary SS777. Presented on March 6, 2021.