Covid-19: five minutes to understand the disappointment of Molnupiravir in France – archyde

the Molnupiravir will ultimately not be used. in France by the end of the year, despite the hopes it had initially raised. Health authorities in fact refused on Friday early access to this antiviral drug against mild to moderate forms of Covid-19, judging its effectiveness less than that of existing treatments. France had however pre-ordered hundreds of thousands of these capsules, developed under the name Lagevrio by the Merck laboratory, with the aim of treating 50,000 patients. We take stock.

What does the Haute Autorité de santé say?

MSD France, the subsidiary of the American laboratory Merck, requested early access – a procedure which allows a drug to be prescribed quickly – for adults infected with the SARS-CoV-2 virus and presenting mild to moderate forms but having a risk factor for develop a severe form of the disease.

But according to the High Authority for Health (HAS), “the efficacy results put forward by the laboratory are less good than those of the available treatments”. They would only reduce the risk of the disease progressing to a severe form by 30%, while some monoclonal antibodies are 80% effective. “Access to Lagevrio in the city risks causing a loss of opportunity for patients, compared to access to more effective treatment,” therefore considers the HAS. In addition, the health authority considers that the impact of treatment on reducing the presence of the virus in the patient “has not been demonstrated”.

How is this a major disappointment?

” There is a game changer, it’s Molnupiravir ”, assured Olivier Véran on October 26, during his hearing before the Senate. This drug has shown that “when taken early in symptomatic people”, it “could reduce the risk of severe form by around 50%”, continued the Minister of Health, confirming having pre-ordered “50 000 doses ”. At the beginning of October, the American laboratory had announced that its treatment reduced the risk of hospitalization or death by half compared to placebo in its interim phase 3 analysis of the MOVe-OUT clinical trial.

Scientists, however, remained cautious. “These first data had surprised us”, nuance with the Parisian professor Frédéric Adnet, head of the emergency department at the Avicenne hospital (Seine-Saint-Denis). They seemed “out of step with the conclusions of the first study that we had read and which was particularly interested in the decrease in viral load under Molnupiravir. “After five days of treatment,” the virus was not isolated from any of the participants receiving 400 or 800 mg of Molnupiravir, against 11.1% of those receiving the placebo “, indicated this study. “We therefore did not expect to see a result as important” as that obtained in the interim analysis of phase 3, or 50% reduction in serious forms, continues Frédéric Adnet.

The latest results communicated at the end of November by the Merck laboratory, those of the final analysis of the MOVe-OUT study, cooled the most enthusiastic: 48 of the 709 patients who received the treatment and 78 of the 699 patients included in the placebo group were hospitalized or died after have been infected. The risk is therefore reduced by 30% if the drug is taken. “The final results show a much lower efficiency than the interim analyzes and the results on patients who did not participate in the interim analyzes are not good, or even bad,” notes Mahmoud Zureik, professor of epidemiology and public health at the University of Versailles Saint-Quentin-en-Yvelines and director of Epi-Phare, for whom the decision of the HAS does not “come as a surprise”.

Will France have to pay for the doses ordered?

No, assures the Ministry of Health, which had ordered enough to treat 50,000 patients with Molnupiravir. “The nature of the contract provides for orders to be triggered only in the event of early authorization for deployment. “The High Authority of Health having refused this authorization of early access,” we will not receive and will not have to pay these ordered doses “. In the United States, where the United States Health Agency (FDA) ruled on December 1 in favor of the Merck pill, the treatment costs around $ 600 per patient, at two doses per day for five days.

Is this refusal final?

The Ministry of Health indicates to have “taken note” of the decision of the HAS and adds however that “exchanges with the European Medicines Agency (EMA) continue”. “A European decision concerning the marketing authorization application is expected at the beginning of 2022”, specifies the ministry.

What does Merck say?

The MSD France laboratory also “took note” of this refusal and said it regrets “that the clinical data provided at this stage did not allow the HAS” to accede to its request. “The efficacy demonstrated by Lagevrio in clinical trials confirmed the additional benefit that it could bring to the arsenal of the fight against the Covid-19 pandemic, especially since it allows simple treatment in the city. “, Pleads in particular its president, Clarisse Lhoste, quoted in a press release of the group.

“We hope that the complete data of the study which were not yet available, as well as the new data collected in the European countries which have already taken the decision to give access to Lagevrio, will be able to help answer the questions raised by the French health authorities ”she underlined.