What other treatments after molnupiravir may be available soon?

After the Merck laboratory and its treatment with a pill against Covid-19, molnupiravir, authorized in the United Kingdom on Thursday, November 4, the American Pfizer in turn announced, on Friday, November 5, very positive results for its pill against Sars-Cov-2, paxlovid. But the two American groups are not the only ones looking for effective drugs against the virus. Franceinfo takes stock of the treatments being developed.

>>> Treatment against Covid-19: four things to know about molnupiravir, of which France has ordered 50,000 doses

Paxlovid, an oral treatment developed by the American laboratory Pfizer

This medicine, like molnupiravir, is part of antiviral therapy. That is, it works by reducing the ability of a virus to replicate, thus slowing the development of the disease. This remedy has the significant advantage of being easy to use, because it can be taken at home, orally, unlike other treatments administered by intravenous infusion, such as bitherapies of monoclonal antibodies, which require a rather heavy logistics: nursing staff, for one hour at the hospital, then one hour of follow-up care, as reported Le Monde (article for subscribers) in June. Another negative point: their cost. These treatments cost “between 1,000 and 2,000 euros per dose”, specified the daily.

The results of the first tests are very encouraging. Paxlovid has been shown to be 89% effective in adults at high risk of developing a severe form of the disease to prevent the risk of hospitalization or death, according to interim clinical trial results released on Friday. By comparison, molnupiravir halves the risk of hospitalization.

The Pfizer laboratory announced on Friday that it intends to provide these results. “as soon as possible” to the US Medicines Agency (FDA) for authorization. Pfizer boss Albert Bourla then said the same day on CNN that he hoped the filing could take place. “before Thanksgiving”, i.e. November 25. These promising results have prompted the American president to “already” Reserve “millions of doses”, he said Friday in a speech.

Fluvoxamine, an oral antidepressant

Fluvoxamine has two advantages. Already in the public domain and present on the market as an antidepressant and as a remedy for obsessive-compulsive disorders, it can be taken orally and at reduced cost (less than 4 euros per box of 15 tablets). According to a study published Thursday, October 28 in the Lancet Global Health (link in English) – a publication linked to the reference journal Lancet but distinct from it – conducted by researchers in Brazil, this antidepressant is able to reduce hospitalizations in patients with Covid-19 and at risk of severe forms.

What does the study say? Researchers have measured how many Covid-19 patients were eventually hospitalized after 28 days or had to spend more than six hours in an emergency department on one occasion. In the end, fewer patients treated with fluvoxamine than those on placebo – 11% versus 16% – found themselves in one of these two situations.

However, these results need to be qualified. “This study clearly suggests that fluvoxamine is an effective, safe, inexpensive and fairly well tolerated option for treating non-hospitalized Covid-19 patients”, judges researcher Otavio Berwanger, not associated with the trial, in a commentary also published by the journal. But he points to the limits of the study. According to him, this does not allow to conclude on the effect of the drug to reduce deaths and, even in terms of hospitalizations, his conclusions are weakened by the fact of having mixed two criteria (hospitalization after 28 days and being in an emergency department for more than six hours). “There is a weak and interesting signal in favor of this molecule (fluvoxamine), but we are very far from the miracle drug. The whole stake is to transform the test and to see if it really has an incidence on the serious forms “, summarizes Frédéric Adnet, head of emergencies at the CHU Avicenne in Bobigny, and researcher at Inserm, in The Parisian.

AstraZeneca AZD7442, by intramuscular injection

AZD7442 is a medicine made from a combination of long-acting monoclonal antibodies. These synthetic antibodies are directed against the spike protein of the virus and were selected for their ability to neutralize it thanks to a synergistic action, Inserm detailed in a press release dated April 21. Unlike the treatments mentioned above, the one developed by AstraZeneca is not administered orally but by intramuscular injection.

The treatment is both effective against the disease, but also in prevention of it in fragile people, announced the laboratory at the beginning of October. In the process, the European Medicines Agency (EMA) said Thursday, October 14, that it had started to evaluate this treatment, paving the way for a possible authorization for the use of the drug in the European Union.

On the results side, patients who were not hospitalized and had symptoms of the disease for seven days or less, saw a 50% reduction in the risk of contracting a severe form of Covid-19 or of dying, explained AstraZeneca in an early press release. October, and this rate rises to 67% for treatment given within five days of the first symptoms.

Ronapreve, injected intravenously, from the Swiss laboratory Roche

Designed by the biotechnology company Regeneron and marketed by the Swiss laboratory Roche under the name Ronapreve, this treatment combines two so-called monoclonal antibodies, casirivimab and imdevimab. This treatment should be injected intravenously. Like AstraZeneca’s AZD7442, Ronapreve is intended for the treatment and prevention of Covid-19.

This drug has already been authorized in France at the beginning of August, for a period of five months. On the European side, Roche filed an application with the EMA on October 11 for marketing in the European Union. EMA “could issue an opinion within two months”, then specified the agency. As for the World Health Organization (WHO), it recently officially recommended this treatment against Covid-19, but only in certain specific cases.

It should be noted that this treatment promises to be expensive. In recent months, NGOs have denounced the high price of Ronapreve, which they estimated at around 2,000 dollars (1,700 euros) per dose, AFP reported on 11 October.

XAV-19, from the French company Xenothera, “effective against variants”

Developed by the Nantes biotech Xenothera, the XAV-19 treatment is intended for patients with moderate Covid, to prevent the worsening of the disease and a transfer to intensive care. “When you receive XAV-19, you are protected for more than ten days, it diffuses into the lungs and in particular prevents all pneumonia. It is demonstrated, these are recent results. This shows the interest of the product. for patients who have mild pneumonia, so as to avoid any aggravation and any risk of going to intensive care “, specified Odile Duvaux, the president of Xenothera, on France 3 Pays-de-la-Loire. XAV-19 is a synthetic polyclonal antibody developed by biotech on the basis of its glyco-humanized antibody technology, that is to say antibodies of porcine origin, which have been modified.

It is thanks to this technology that the XAV-19 presents results “very interesting”, including with regard to variants. “Because of its polyclonal nature, it is quite effective against variants. It is even surprisingly even more effective on the Delta variant than on the variants which have circulated previously.” Efficacy results on patients are “Analyzing”, specifies Odile Duvaux. “So far we only have preliminary results to talk about it”.

Odile Duvaux announced in September on franceinfo that XAV-19 could be available to patients in France “at the end of 2021”. On May 11, the company announced that it had signed a pre-order contract with the French government for 30,000 doses, the amount of which would amount to 5 million euros, reported the regional daily. The Telegram. But for now, we don’t know when that will be possible. The society “does not master” the exact timing of availability, explained the president of Xenothera to franceinfo. “We are in the regulatory phase to obtain an early access authorization by the French authorizations”, she added.


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