Sars-CoV-2 will not disappear, we must learn to live with it. The scientific community is largely in agreement in stating that, once the health emergency is over, we will not be able to consider ourselves immune and safe anyway. This is why research on therapies and vaccines (also effective against the new variants) does not stop. Rather. On 29 June, the European Commission made an important announcement: in the coming months five new treatments for Covid could be authorized. Four are based on monoclonal antibodies, already under review by the European Medicines Agency (Ema). Then there is an immunosuppressant already on the market (Eli Lilly’s baricitinib), the use of which could be extended for the disease caused by the coronavirus. “We are taking the first step towards a wide range of therapies for the treatment of Covid – he said Stella Kyriakides, EU Commissioner for Health -. Vaccination is progressing at an increasing rate, but the virus will not go away and patients will need safe and effective treatments. We aim to identify more cutting-edge candidates in development and to authorize at least three new therapies by the end of the year. “
Drugs under review
The four monoclonal antibodies under review are: the combination of bamlanivimab ed etesevimab by Eli Lilly; the combination of casirivimab e imdevimab by Regeneron-Roche; regdanivimab of Celltrion; sotrovimab by GlaxoSmithKline-Vir Biotechnology. A group of experts will identify the product categories and select the most suitable therapeutic candidates for each category. Target: have at least three new therapies authorized by October and possibly two more by the end of the year. In Italy some monoclonal antibodies – bamlanivimab, il mix bamlanivimab-etesevimab e il mix casirivimab-imdevimab – were temporarily authorized by decree of the Minister of Health last February, for the treatment of mild to moderate Covid in adults and children. Some local health authorities have launched experiments to administer monoclonals at home.
Target: the Spike protein
So will these drugs help us, together with vaccines, to get out of the Covid emergency? But let’s take a step back. How do they work? “The monoclonal antibody recognizes only one” epitope “(a small group of amino acids) of the virus —explains Giuseppe Nocentini, professor of Pharmacology at the University of Perugia and member of the Italian Society of Pharmacology -. All monoclonals target la proteina Spike: by blocking it, they prevent the virus from entering our cells. If the virus spontaneously changes the target sequence, the drug loses its effectiveness. That’s why they are often used associations of two antibodies: the double mutation is decidedly more unlikely ».
The advantages of the antibody Gsk
Sotrovimab, by GlaxoSmithKline (Gsk) and Vir Biotechnology, was recommended on May 27 by EMA, the European Medicines Agency, as an early treatment for adults and adolescents (aged 12 and over and weighing no less than 40 kilos) with mild symptoms, which do not require oxygen and are at risk of having severe forms of the disease. The drug, like the other monoclonals in use, is administered intravenously. In studies sotrovimab was shown to reduce the risk of death by 85% compared to placebo: a result that made it possible to stop the enrollment of patients, thanks to the evident evidence of efficacy. The evaluation of the EMA is therefore concluded, but the review procedure (rolling review), which began on May 7, is still ongoing. Once completed, it will be possible to authorize the sale throughout the European Union. Education in vitro have shown that sotrovimab is effective against several variants. Sotrovimab has indeed as its target an “epitope” of the Spike protein that is less likely to mutate over time.
More than 6 thousand patients treated
In Italy they are over 6,100, from 10 March to today, Covid patients who have received monoclonal antibodies, authorized in an emergency by Aifa, the Italian drug agency. But, thanks to the vaccination of elderly and frail subjects (for example diabetics and obese), weekly prescriptions continue to drop: between 18 and 24 June, they were 57, 11% less than the previous week (64). These are the data from the Report on monoclonal antibodies of the Italian Medicines Agency. Lazio is the region that has administered the most doses (823), followed by Veneto, Tuscany and Puglia. Monoclonals are reserved for frail people, recently infected with Sars-CoV-2 and without severe symptoms. Most of the patients in Italy have received the combination of bamlanivimab and etesevimab at Eli Lilly.
Doubts about efficacy
In the last few days they have emerged though doubts about the efficacy of the bamlanivimab-etesevimab mix against some variants. In the United States, the Assistant secretary for preparedness and response (Aspr), an office that is part of the Department of Health, and the Food and drug administration (Fda), have suspended the distribution of the Eli Lilly and etesevimab combination until further notice. alone, authorized as an emergency in February. The FDA also asked for alternative therapies to be used. All this because some tests in vitro showed that Eli Lilly’s monoclonal antibodies are not effective against variants P.1 (identified in Brazil) and B.1.351 (“South African”), whose diffusion in the US is 11% and tends to increase. The same tests instead showed that Regeneron’s monoclonal combination maintains activity against P.1 and B.1.351.
The all “Italian” antibody
Meanwhile, phases 2/3 of the clinical trial of “MAD0004J08”, the human monoclonal antibody identified by Mad Lab, a research team of the Toscana Life Sciences Foundation coordinated by Rino Rappuoli. In fact, clinical phase I, carried out at the Spallanzani Institute in Rome and at the Clinical Research Center in Verona on 30 healthy volunteers, was completed. Phases 2/3 involve 14 centers in Rome, Piacenza, Trieste, Pavia, Foggia, Siena, Vercelli, Verona, Milan, Parma, Pisa, Florence, Naples, Avellino. Tests involve over 800 patients with Sars-CoV-2 infection, swab positive for no more than 72 hours, asymptomatic or moderately symptomatic. After administration of the antibody, patients are followed up at home and with periodic hospital visits. Therapy is administered through an intramuscular injection, “Thanks to the extreme neutralization power shown so far in preclinical studies, which allows the use of a lower dosage than other similar treatments currently in use”, explain the researchers.
Tocilizumab for the hospitalized
Another novelty comes from the United States, where the Food and Drug Administration (Fda) emergency approved the monoclonal antibody tocilizumab (from Genentech, a subsidiary of the Swiss Roche group), already employed in the treatment of rheumatic diseases, for the treatment of Covid in hospitalized adults and children (aged 2 years and over), on cortisone therapy and who need oxygen, mechanical ventilation or extracorporeal circulation. The FDA’s decision is based on the results of four studies that evaluated tocilizumab in more than 5,500 patients. The drug – used for some time for Covid on an experimental basis, also in Italy – is not indicated for patients treated at home. In clinical trials, added to routine cortisone therapy, it has been shown to reduce the risk of death, time spent in hospital and the likelihood of being ventilated. Tocilizumab brings down inflammation by blocking the receptors of interleukin-6, a protein produced by the immune system. On June 17, the Italian Medicines Agency (Aifa) also included tocilizumab in the list of drugs for the treatment of adults hospitalized with severe Covid or with high levels of inflammation indices.
Monoclonal antibodies: the latest news
June 30, 2021 (change June 30, 2021 | 16:56)
© REPRODUCTION RESERVED