Effective treatment for severe covid reserved in the United States

“A scandal.” This is how Antoine Flahault, director of the Institute of Global Health at the University of Geneva, describes on Twitter, the decision of Lilly Laboratories. The US pharmaceutical company has developed the only monoclonal antibody, bebtelovimab, which remains completely effective in neutralizing Omicron’s BA.4 and BA.5 sub-variants, as shown by a recent study by a Columbia University team that was pre-published on the BioRxiv site. Problem: Lilly refuses to market her treatment outside the United States, where 600,000 doses have already been ordered.

Why is this important? Because the BA.4 and BA.5 sub-variants, more transmissible than their predecessors, have recently seen dramatic progress in the world, becoming dominant in the United States, South Africa, but also in Portugal, which sees currently an increase in confirmed cases, hospitalizations and Covid-19-related deaths. In Switzerland, these sub-variants now account for almost 50% of new transmissions, according to Christian Althaus, an epidemiologist at the Institute of Social and Preventive Medicine at the University of Bern. According to the latter, 65% of the Swiss population still has immunity to BA.5, but 15% of the population could be infected with the newcomer within the next few weeks.

Also read: Ten questions to understand the bounce of covid in Switzerland

On the other hand, Omicron also appears to have increased its pathogenicity as its sub-variants appear. According to a study by the University of Tokyo, which evaluated the characteristics of the BA.4 and BA.5 sub-variants, the latter would replicate more effectively in human lung cells. In hamsters, lung damage would be more severe during infection with these two new sub-variants, compared with BA.2. Hence the importance of having effective treatments for people at high risk of developing severe forms of the disease or in immunocompromised patients.

Forgotten treatments

“Lilly told us she didn’t want to share her antibody to do clinical trials in Europe or market doses,” said Antoine Flahault. It’s very worrying because we won’t have an effective neutralizing antibody to treat the most at-risk infected people. ” The Federal Office of Public Health, for its part, had already inquired in February about the possibility of supplying bebtelovimab to Lilly, who replied that she “did not intend to make the drug available in outside the United States ”. Negotiations are underway between the pharmaceutical company and the US government for the supply of additional doses under an amended purchase agreement. But nothing else.

What are the reasons for this decision? When contacted, the pharmaceutical company, which has an office in Switzerland, replied succinctly that it was “continuing to assess the need and demand for [son] treatment in other markets. ” However, hypotheses emerge: “Lilly launched a first generation of monoclonal antibodies against SARS-CoV-2, but this treatment quickly lost its effectiveness against new variants,” said Alexandra Calmy, an infectiologist at the University Hospitals of Geneva. HUG). Is it possible that the company has been scalded by this experience and no longer wants to invest so much in this therapeutic field? It is very difficult for us, as a doctor, not to have a medicine that seems to be effective against BA.4 and BA.5. ”

Also read: Covid-19: Towards a new wave of variants BA.4 and BA.5 this summer?

In fact, as Antoine Flahault points out, most of the monoclonal antibodies placed on the market have been forgotten one after the other, collateral victims of the various variants of SARS-CoV-2. “As soon as mutations in the virus’s spike protein appear, there is a decrease in the activity of monoclonal antibodies, which forces us to constantly adapt to our clinical decisions,” said Oriol Manuel, an assistant physician in the Department of Infectious Diseases. of the Vaud University Hospital Center (CHUV). Proof of the fragility of these treatments: “The monoclonal antibody developed by Regeneron was approved by Swissmedic (Swiss Institute for Therapeutic Products) on the same day that it was discontinued in the clinic, when it became completely ineffective. against the Omicron variant, ”recalls the specialist.

An antiviral as a glimmer of hope

Inaccessible Lilly monoclonal antibody, what are doctors now relying on to care for patients at risk of developing severe forms of Covid-19? Fortunately, the bad news did not follow, and Swissmedic authorized the use of Paxlovid, the oral antiviral developed by Pfizer, for a limited period of time, almost 5 months after the European Medicines Agency (EMA). Clinical studies have been shown to be very effective against hospitalizations, “Alexandra Calmy said. “It simply came to our notice then.

“The fact that Paxlovid has been authorized reassures us,” said Oriol Manuel. For now, this treatment is still limited to patients at very high risk for severe complications of Covid-19, but data from other countries show that it could possibly also be used in more patients. . » His limitation? Possible interactions with certain medications for heart disease or immunosuppressants. “This requires a thorough discussion of the benefits and risks of such treatment,” said the doctor. But it will still make it much easier for patients at risk to be cared for. ”

The remaining therapeutic arsenal still includes intravenous Remdesivir antiviral, which is currently being tested by oral manufacturer Gilead in early stages of clinical trials. Or Evusheld, a combination of monoclonal antibodies used in prevention in people at high risk for complications, and perhaps soon in the early treatment of Covid-19.

Industrial dependence

In the face of developments in antiviral drugs against Covid-19, what good are monoclonal antibodies? “They can be useful in highly immunosuppressed patients,” says Oriol Manuel. The antiviral decreases the viral load in the body and prevents immediate complications, but recurrences are not ruled out when patients do not have enough antibodies to fight an infection. These antibodies could give them some immunity. ” “Given the race against the variants, you absolutely have to have treatments with different mechanisms of action, otherwise you play the lottery,” says Alexandra Calmy.

The example of bebtelovimab also highlights the question of Europe’s independence with regard to Covid-19 treatments. “Europe may understand that it has lacked the audacity and risk-taking in the development of treatment for Covid-19,” said Antoine Flahault. There is no ambitious R&D program in this area. ” And the epidemiologist reminds that the best strategy to deal with the rebound of infections and prevent an increase in mortality is to test and treat.

“Prevention is also very important, especially in EMS, where the mask should again be worn by caregivers and visitors,” said the Geneva epidemiologist. Vaccination would also prevent a rise in mortality with a welcome fourth dose to boost the immunity of those whose long-term booster dose. “

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