Molnupiravir fails to beat standard of care in trial

3 minute read

The covid antiviral showed no benefit in death or hospitalisation rates, though it shortened recovery time for survivors.

Questions have been raised about the effectiveness of antiviral molnupiravir against Covid, with new data suggesting it’s no better than usual care at reducing hospitalisation and death.

Preliminary analysis of data from the randomised, controlled open-label PANORAMIC trial – published on the non-peer-reviewed preprint server SSRN – found twice-daily molnupiravir for five days, in addition to usual care, had no significant effect on the rate of hospitalisation or death among more than 25,000 adults aged over 50 years or with at least one comorbidity.

The study failed to show any benefit even among subgroups such as those with various comorbidities including diabetes and obesity, from different age groups or with varying duration of symptoms before starting treatment.

Participants given molnupiravir did report a shorter recovery time – around four days less than for participants who received usual care only – and this was seen across all subgroups.

The cohort were community-based, the vast majority were vaccinated, and the study took place during the first major Omicron surge in the UK.

Meanwhile, another recent study involving nearly 20,000 adults aged over 40 years – around 1000 of whom were treated with molnupiravir – found no significant benefit among younger adults, but a near-halving of hospitalisation rates and nearly 75% reduction in deaths among those aged over 65 years.

The PANORAMIC findings contradict those of the earlier manufacturer-funded MOVe-OUT trial, whose interim analysis after 50% of patients had been recruited suggested the treatment halved the risk of hospitalisation or death from covid. However the final analysis found a trend favouring placebo, and no difference in mortality between the treatment and placebo arms.

Commenting on the findings, infectious diseases physician Associate Professor Paul Griffin said the difference between the two studies showed how things can change from well-controlled clinical trials to the real-world setting. “Sometimes the real-world experience doesn’t mirror that; there are more variables, it’s less well controlled and with different populations,” said A/Professor Griffin, Director of Infectious Diseases at Mater Health Services in Brisbane. “Whether it’s selecting the right patients but also getting therapy to them at the right time, those things can certainly have a big impact in what we see.”

Researcher Dr Kyle Sheldrick, from Merunova in Sydney, was one of several experts who raised concerns about the interim results of the MOVe-OUT trial and the fact that those results were used by justify the emergency use authorisations granted by the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency.

“It was very clear in MOVe-OUT that the drug had stopped working halfway through the trial without a clear reason as to why,” Dr Sheldrick told The Medical Republic.

Given this, Dr Sheldrick said the results of the PANORAMIC trial are disappointing but not surprising. “I don’t think it’s possible to look at this trial and still come up with a reasonable conclusion that this drug does anything at all for stopping hospitalisation or death,” he said.

Dr Sheldrick suggested that the reason for the failure could be that the variant or strain present during the early phases of study have since died out and subsequent Omicron strains are more resistant to the antiviral.

In Australia, molnupiravir is approved for treatment of covid in at-risk adults who are unable to take Paxlovid (nirmatrelvir-ritonavir). However given the drug is under provisional registration, the manufacturer is still required to submit further safety and efficacy data for full registration.

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