Hope in sight for an oral antiviral pill against COVID-19

The oral antiviral drug molnupiravir, given for 5 days, eliminated SARS-CoV-2 in the nasopharynx of patients with COVID-19, interim results of a phase IIa study have shown, boosting hopes for its potential use in the outpatient setting. 

On day 5 of treatment, there was a reduction in positive viral culture in patients who received molnupiravir (all doses) vs placebo (nominal p=0.001, not controlled for multiplicity). No safety signals have been identified. Of the four serious adverse events reported, none was drug-related.

Molnupiravir inhibits the replication of multiple RNA viruses as shown in preclinical studies. The drug is active in several models of SARS-CoV-2 for prophylaxis, treatment, and limiting viral transmission, even for SARS-CoV-2 and MERS. 

Promising data, yet too early to tell

Experts say it is too early to tell if molnupiravir can keep COVID-19 patients out of the ICU. “It has the potential to be practice-changing,” commented Dr Carlos del Rio, professor of medicine at Emory University in Atlanta, Georgia, US, who is not part of the study. “It’s not practice-changing at the moment though, we are not there yet.”

The data for molnupiravir may be promising, “but we need to see if people will get better from the actual illness,” said Dr Wendy Painter from Ridgeback Biotherapeutics, who presented the findings at CROI 2021.

Virus-free at day 5

The results were based on laboratory values of 78 patients who had an infection at baseline. By day 3, 28 percent of patients in the placebo arm had SARS-CoV-2 in their nasopharynx vs 20.4 percent of those receiving any dose of molnupiravir. [CROI 2021, abstract SS777]

On day 5, none of the patients who received molnupiravir had detectable SARS-CoV-2 in the nasopharynx whereas 24 percent who received placebo had it.

Differences in the SARS-CoV-2 load were apparent midway through the 5-day course. On day 3, about 36.4 percent of patients taking molnupiravir 200 mg had detectable virus in the nasopharynx, 21 percent had it in the 400 mg group, and 12.5 percent in the 800 mg group.

Reductions in the SARS-CoV-2, though evident in the 200 mg and the 400 mg groups, were only statistically significant for molnupiravir 800 mg. While details and study size are limited, a measurable drop in infection duration is significant as it means a smaller chance of transmission or severe symptoms. 

The study included adult patients being treated at an outpatient clinic, with fever or respiratory symptoms, and confirmed SARS-CoV-2 infection on day 4. They were randomly assigned to molnupiravir 200 mg, 400 mg, or 800 mg. The 200 mg arm was matched one-to-one with a placebo-controlled group. The other two groups had three patients in the active group for every one control.

Molnupiravir was administered twice daily for 5 days and followed for a total of 28 days to check for complications or adverse events. At days 3, 5, 7, 14, and 28, patients had nasopharyngeal swabs taken for reverse transcription-polymerase chain reaction (RT-PCR) analysis.

What’s good about the pills, according to Painter, is that they don’t require low temperature for storage, unlike vaccines.

The full study results remain blinded and will be shared as they become available. Phase II/III efficacy and safety studies of molnupiravir for hospitalized and non-hospitalized patients are underway.

Oral antivirals desperately needed

So far, only the nucleoside analog remdesivir is US FDA-approved for COVID-19 in hospitalized patients. The cost of a 5-day course of intravenous remdesivir ranges from $2,340 to $3,120 in the US.

“There’s an urgent need for an easily produced and administered antiviral drug in those who contract the virus,” Painter said. Oral formulations are desperately needed. Were a pill-based treatment is made available, lives would be saved, and hospital beds could be freed for patients who need them most.