What are anti-Covid monoclonal antibodies, and which ones are on the way?

What are anti-Covid monoclonal antibodies, and which ones are on the way?

It is one of the most promising therapies against Covid 19: artificially produced antibodies to defeat the virus. Let's see which ones are currently in development

(illustration: Getty Images) Donald Trump is one of the great protagonists of this pandemic. He will certainly remain famous for his bluster, his sudden changes of opinion about the virus, and his surprise endorsements to this or that miracle therapy, which then tends to prove (inevitably) dramatically useless. Finally, his recent illness, and the consequent quick recovery, have focused the spotlight on monoclonal antibodies, heralded by the US president as a cure-all, which he promises to provide free to all Americans to defeat the epidemic once and for all . And if the criticisms, even in this case, were not long in coming, the truth is that monoclonal antibodies are really the most promising therapeutic strategy in development, and could save the lives of many patients (here too). before finally seeing an elusive vaccine arrive. Let's see what it is, and which ones are the most promising currently in development.

Monoclonal antibodies

An antibody is a molecule (or rather a glycoprotein) which has the task of recognizing invaders, and in particular pathogens such as bacteria and viruses, to allow our organism to neutralize them. The immune system produces a multitude of different types, ready to identify the enemy with a key / lock system: when the binding site on an antibody finds a complementary antigen on a pathogen (or other external element) that is invading the our body, the immune system begins to mass produce the antibody in question, and in this way (hopefully) the infection is defeated. As we said, there are billions of antibodies, and not all of them are equally effective against a potential invader. The body also takes time to produce them in sufficient quantities to eradicate an ongoing disease. Two problems that can be solved by producing monoclonal antibodies: artificially produced antibodies to be all identical to each other, and therefore with exactly the same ability to neutralize their own antigen. It is enough to identify a particularly effective antibody, and by producing perfect copies of it in mass, we find in our hands a very powerful drug, with which to attack tumors, malfunctioning elements of our immune system (it happens for example in the therapy of many autoimmune diseases) and obviously also bacteria and viruses such as Sars-Cov-2.

In the case of the current pandemic, it is easy to imagine the usefulness of such a drug. Covid survivors are highly likely to have developed particularly effective antibodies against the virus. By identifying them, and transforming them into monoclonal antibodies, it is possible to give all patients the same chances of success given by chance to these lucky ones. This is obviously a trial and error procedure: initially the antibodies are tested in vitro, to verify their ability to inhibit the replication of the virus; the best are therefore tested on animal models and human volunteers to ensure that they do not have particularly harmful side effects; and finally we reach the patients, to ensure that they really have clinical efficacy. Obviously, only a fraction of those identified in the laboratories reach this last stage of development. But thanks to the enormous efforts (and the rain of funding) put in place by governments and pharmaceutical companies around the world, there are already three currently being tested with phase 3 trials, at the end of which, in case of satisfactory results, it is possible to apply for marketing authorization.

Regeneron

The monoclonal antibodies that Trump has personally tested are those produced by the American biotech Rege ne ron, and are perhaps the ones currently closer to the goal: the pharmaceutical company announced in recent weeks the preliminary results of its trial, in which Regn-Cov2 (their cocktail of monoclonal antibodies) would prove safe and effective, in particular, at least for now, in non-hospitalized patients in the early stages of the disease. Regeneron has already asked the FDA (the American drug agency) for an accelerated authorization procedure for its drug, and with an endorsement as weighty as that of the president, many believe the agency’s approval is likely. The drug in question is a cocktail consisting of two monoclonal antibodies, one isolated from a Singapore patient, and another obtained in the laboratory by inserting the coronavirus spike protein into the body of a mouse that has been generically modified to provide it with a human immune system. The data presented by the company actually seem encouraging, and suggest that the drug could prove useful even in the case of the most serious patients. However, doubts are not lacking: in fact, many believe it impossible for Regeneron to be able to produce the drug in sufficient quantities even for the American market alone. Currently, the company reports that it has stocks for around 50,000 treatments, and promises to produce enough for around 300,000 patients within a few months. According to the estimates of some experts, however, drugs for at least 3-400 thousand therapies every month would be needed to keep up with the needs of the United States alone.

Eli Lilly

Practically in step with the rival Regeneron we find a big in the pharmaceutical industry like Eli Lilly. His drug, currently known as LY-CoV555, was shown to reduce the risk of hospitalization for patients with moderate symptoms by 72% in a placebo trial involving 452 patients. Also in this case, the company requested an accelerated authorization procedure, but the first problems have emerged in recent days. The US government has in fact blocked an ongoing trial with LY-CoV555 on hospitalized patients, due to a change in the clinical conditions of patients treated with the drug considered dangerous. More is not known at the moment, but it is likely that, even if the trial resumes in the coming weeks, the approval of the drug will be at least slowed down by this hitch.

Astrazeneca

Best known for its Covid vaccine (the one that would also be produced in the Pomezia plants), the British drug multinational Astrazene ca also has a monoclonal antibody at an advanced stage of development. It is identified for now with the initials AZD7442, and according to the information released by the company, it has the particularity of having been developed using a technology that allows to extend the survival of antibodies in the body. If it becomes a full-fledged drug, it could provide protection against Covid for a period of 6-12 months. Far longer than the other two rivals, and long enough to transform the therapy into a sort of seasonal vaccine (a strategy called passive immunization, to distinguish it from the active one guaranteed by a vaccine). The company has announced the launch of two phase 3 trials for its monoclonal antibody, which will involve over 6,000 patients, but even if the results are encouraging, the drug is unlikely to reach the market before next year.

Prometheus

Another particularly interesting experience is that of the international collaboration Prometheus, which since 2019 has been working to study new therapies against coronaviruses, and in particular those that (such as Sars-Cov-2) derive from bats. In their case, the monoclonal antibody under development will not arrive in a phase 3 trial before the second half of December. But despite the delays, it is anxiously awaited by the scientific community for two important reasons: it would be effective for over six months and, above all, it promises to be effective on all types of coronavirus, and could therefore prove to be valuable in the future in case of new pandemic spillovers.

Toscana Life Sciences

Also in Italy we are working in the field of monoclonal antibodies. The Monoclonal Antibody Discovery Lab of the Toscana Life Science Foundation in Siena is in charge of it, under the supervision of Rino Rappuoli. In August, the researchers announced that they had isolated 3 extremely promising antibodies, and just in the last few days it was confirmed that one of them was chosen for the development of a drug that, according to its creators, promises to prove to be the most powerful among those under study, with both preventive and therapeutic efficacy (currently studied on hamsters) against the virus. Clinical trials, in this case, should begin by the end of the year.

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