EMA refuses lagevrio marketing authorisation for treatment of COVID

28th February 2023

The EMA has recommended against issuing of a marketing authorisation for lagevrio (molnupiravir) for the treatment of adults with COVID-19

Lagevrio was refused a marketing authorisation by the European Medicines Agency on the 23rd February 2023, for the treatment of adults with COVID-19. However, the manufacturer, Merck Sharp & Dohme B.V., may ask the EMA to re-examine its opinion within 15 days.

Data on lagevrio had initially revealed how treatment with the drug treatment led to a reduction in the risk of hospitalisation or death among unvaccinated individuals with at least one risk factor for more severe disease. However, with the introduction of widespread COVID-19 vaccination, the question of whether the drug would still offer benefit to at-risk and vaccinated patients, remained unanswered. Nevertheless, while there was some preliminary data which suggested that the drug retained anti-viral activity against several COVID-19 variants, even among those who had been vaccinated, more definitive data were required.

The PANORAMIC trial was designed to examine if the addition of lagevrio to usual care could reduce hospital admission and COVID-10-related mortality among patients who had been vaccinated against the virus. PANORAMIC was a huge, randomised trial, recruiting over 26,000 patients and assigning nearly 13,000 to lagevrio. The results clearly showed that lagevrio failed to reduce the frequency of COVID associated hospitalisations or deaths in high-risk, vaccinated individuals. In fact, the authors of the PANORAMIC trial went as far as to say that the observed avoidance of both hospitalisation and mortality due to COVID-19 were largely as a result of extensive vaccination.

In a letter explaining the decision, the EMA noted that after an evaluation of the data provided by the manufacturer, it was concluded that clinical benefits of the drug among patients who are not receiving supplemental oxygen but still at risk of developing severe COVID-19, could not be demonstrated. In fact, the EMA stated that ‘based on the totality of the data, it was not possible to conclude that Lagevrio can reduce the risk. of hospitalisation or death or shorten the duration of illness or time to recovery in adults at risk of severe disease.’ Adding that ‘it was not possible to identify a specific group of patients in whom a clinically relevant benefit of Lagevrio could be demonstrated.’