NOT ONLY vaccines. The European Union strategy against Covid-19 also passes by medications. The European Commission has recently announced a first portfolio of five treatments that may soon be available in the Union. Four of these therapies are monoclonal antibodies in rolling review by Ema. The fifth, an immunosuppressant already authorized for other indications, could receive the extension for the treatment of Covid-19 patients.
No specific drug for the virus
Effectively treating Covid-19, the disease that develops following the infection with Sars-Cov-2, immediately proved to be a feat. Faced with a completely new virus – and the resulting disease – research went by trial and error. While on the one hand they tried to control the symptoms of the disease through the use of anti-inflammatories, on the other hand the scientists tried – while waiting to develop new drugs – to test “old” antivirals in the hope that they also worked against SARS. Cov-2. Unfortunately, among all those tested, only one proved to be partially effective – and in particular conditions – against the virus. This is why, to date, an approved specific cure that selectively affects Sars-Cov-2 does not yet exist.
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Antivirals in use
The antivirals they are the perfect weapon against viruses. In fact, they are able to interfere with the mechanisms that the virus puts in place to replicate. Being able to act on them, the final result is the blocking of viral growth.
The only one that gave partial results against the coronavirus was Gilead’s remdesivir, an antiviral developed years ago against the Ebola virus. The idea of using it was born from the evidence obtained in the laboratory in effectively countering other forms of coronavirus. While not specific to Sars-Cov-2, the FDA approved the drug for coronavirus-positive patients in October 2020.
The authorization for use was based on data from a clinical study published in May. Although remdesivir does not reduce mortality from Covid-19, the clinical study conducted and which led to the approval has shown that the antiviral is able to shorten the average hospital stay from 15 to 11 days. Results that, according to various insiders, are partial and not exactly comforting. It is no coincidence that the WHO, in February of this year, after analyzing the data of a massive clinical study, ruled that remdesivir “had little or no effect on patients hospitalized with Covid-19”.
In experimentation
Among those being tested – among the over 200 being tested – there is one in particular, molnupiravir (developed by MSD and Ridgeback), which has shown itself to be particularly promising. The results obtained in humans were presented at the last CROI conference. A single pill of the investigational drug molnupiravir taken twice daily for 5 days could clear the SARS-CoV-2 virus from the nasopharynx.
The molecule in question, preventing the virus from replicating, could be useful to administer at the first symptoms to reduce the viral load and therefore limit the damage of the virus. The trial is still in progress and in case of efficacy, according to the first rumors, the drug could arrive on the market by the end of the year.
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Monoclonal antibodies
Another possible strategy in contrasting the virus is that which involves the use of the antibodies developed following a Sars-Cov-2 infection. Initially, this strategy took the form of hyperimmune plasma, a procedure in use for decades that involves the administration of plasma to convalescent patients. However, it is an emergency strategy as it requires that there are people who have become infected. Unfortunately, however, according to the larger study conducted in recent months and recently published by the British Medical Journal, the use of convalescent plasma would not lead to significant results. The conditional is, however, a must since the clinical studies in this regard are still in progress.
The plasma
However, starting from the concept of hyperimmune plasma, research was set in motion in an attempt to find alternative ways to obtain a similar product. And this is the case with monoclonal antibodies. The principle is the same as for plasma but in this case the strategy is to copy and produce on a large scale only the necessary antibodies and in large quantities. Antibodies that can be reproduced industrially in unlimited quantities and for an infinite number of times in order to have a concentrate of the best weapons to target the virus. But be careful to think that monoclonal antibodies are the solution to the coronavirus problem: intravenous administration and at the onset of symptoms are characteristics that enormously limit the use of these drugs.
Among those approved and most widely used is the combination bamlanivimab and etesevimab developed by Lilly. According to data released in March, developed by testing these antibodies on over 700 people, this combination led to an 87% reduction in hospitalizations and deaths related to Covid-19. An excellent result which, however, could no longer be such in light of the new variants that have developed in recent months. It is no coincidence that the FDA has recently “paused” the distribution of the combination. News that could heavily influence decisions in Europe as well.
The other combination that is focusing attention, also in Europe, is casirivimab and imdevimab, both produced by Regeneron. A Phase 3 study last April showed that the combination significantly reduced the risk of hospitalization and death among high-risk patients with Covid-19. Not only that, the administration greatly reduced the duration of symptoms. In addition, another study showed a reduction in deaths in patients with compromised immune systems.
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Another promising monoclonal antibody is sotrovimab, developed by Gsk and Vir Biotechnolog. This antibody has a dual function: it binds the Spike protein of the virus, thus inhibiting the bond between the virus and the body’s cells and manages to eliminate the virus that has entered the cells. Clinical data reported an 85% reduction in the risk of hospitalization or death if sotrovimab is used in the early stages. An important result which was followed by the positive opinion of the CHMP (Committee for Medicinal Products for Human Use) of Ema (European Medicines Agency’s) last May. Since then, member states have been able to decide to use them according to their needs. Finally, the European Commission’s negotiations include Celltrion’s regdanvimab, also a monoclonal antibody that received an opinion from the CHMP.
Turn off inflammation
While waiting for new drugs, there is another category of molecules that has proved useful in preventing complications from Covid-19. One of the main characteristics of Sars-Cov-2 infection is in fact the inflammation that is generated both at the lung and at the systemic level. In severe cases, when the response becomes uncontrollable, the patient undergoes serious complications that can lead to death.
Stopping excessive inflammation is critically important. To obtain this result, more and more studies indicate dexamethasone and its derivatives (corticosteroids) as a useful molecule for this purpose. In a study published in May of over 6,000 people, dexamethasone was shown to be useful in reducing deaths by a third in patients receiving mechanical ventilation and by a fifth in those receiving oxygen therapy. Additional data published in a review of Jama in September showed that dexamethasone is useful in reducing deaths by a third in all Covid-19 patients.
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But there is another molecule that has been shown to help quench inflammation. Baricitinib, a medicine developed by Lilly for rheumatoid arthritis, has been shown to be effective in reducing healing times, primarily for patients with moderate pneumonia who need oxygen support but not mechanical ventilation. Effectiveness essentially due to its ability to extinguish inflammation. For this reason, the molecule has been included by the European Commission in the list of the most promising to limit damage from Covid-19.
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