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This story originally appeared in The Conversation
By Francisco López-Muñoz, the Camilo José Cela University and Jose Antonio Guerra Guirao, the Complutense University of Madrid
The US Food and Drug Administration (FDA)Food and Drug Administration), You have just issued an emergency permit (USA, Emergency approval) for the treatment of COVID-19 with mild to moderate intensity in adult and pediatric patients who have not been hospitalized. The therapy that is still being investigated is based on monoclonal antibodies and is called Bamlanivimab.
Developed by pharmaceutical company Eli Lilly, this therapeutic is a monoclonal antibody that is similar to those that were part of the drug cocktail for COVID-19 given to Donald Trump.
What are monoclonal antibodies?
In general, antibodies are large proteins that make up the immune system, which is necessary to identify and neutralize foreign objects in the body such as bacteria and viruses.
In the special case of monoclonal antibodies (mAbs, from English monoclonal antibodies) are glycoproteins that are produced by the clone of a hybrid cell (which results from the fusion of a single stem cell of the immune system and a tumor plasma cell) and are intended to attack a specific antigen.
Its production is based on the establishment of immortal B lymphocytes that are modified to produce a specific immunoglobulin. Depending on the purity of the immunoglobulin, it can be completely murine, chimeric, humanized, or completely human.
Monoclonal antibodies are carefully selected and directed against a specific molecule that plays a key role in a disease process, and they are often used to treat certain diseases such as cancer or rheumatoid arthritis.
What about neutralizing antibodies?
Neutralizing antibodies are one of the immune system’s possible defense mechanisms against infection.
These antibodies make it possible to counteract and eliminate the action of invading microorganisms, and their activity is triggered, for example, by proteins that are on the surface of viruses and to which they bind to “block” infection.
With this in mind, science has been investigating for some time whether the defense reaction by neutralizing antibodies can induce effective and lasting immunity. In particular, it is investigating whether the antibodies generated by patients who have come into contact with the SARS-CoV-2 coronavirus can be used as the basis for new treatments for Covid-19.
Although neutralizing antibodies are generated when a person has an infection and appears to play an important role in the immune response, their specific role in the Covid-19 cogs has not been fully elucidated.
The studies carried out so far with the SARS-CoV-2 virus show that neutralizing antibodies appear about two weeks after the onset of the infection and that their maximum activity peak would be between the 4th and 6th week. However, there are still many unknowns: It has not been confirmed whether all infected patients produce neutralizing antibodies. What factors determine appearance and activity (age of the patient, severity of infection)? Even if its degree of neutralization is not always sufficient to provide protection, as these are highly variable and cannot be detected in 10-30% of patients.
The entry of SARS-CoV-2 into cells is initiated by the interaction of the receptor binding domain (RBD) of the viral spike (S) glycoprotein with the angiotensin converting enzyme-2 (ACE2), which acts as a receptor for the virus on the Surface of the target cell. The most potent neutralizing mAbs target RBD and some can act simply by competing with the receptor for binding to the S protein.
What is Bamlanivimab?
Bamlanivimab is a neutralizing recombinant monoclonal human IgG1 kappa antibody against the spike protein of the SARS-CoV-2 virus and is not modified in the Fc region.
This agent is approved for the treatment of patients with positive SARS-CoV-2 test results who are 12 years of age or older, weigh at least 40 kilograms and are at high risk of developing severe COVID-19 or hospitalization. . This includes patients who are 65 years of age or older or who have certain chronic conditions. Bamlanivimab is a drug that must be given intravenously. Therefore, patients must go to a hospital for administration.
While the safety and effectiveness of this investigative therapy continues to be evaluated, clinical studies have confirmed that bamlanivimab compared to placebo reduces hospital or emergency room admissions related to Covid-19 in patients at high risk of disease progression within 28 days of starting treatment. For this reason, use is recommended in the early stages of the disease, preferably in the first 10 days after the symptoms of the disease appear.
However, bamlanivimab is not approved in patients hospitalized for COVID-19 or in need of oxygen therapy, as no significant benefit from treatment with this monoclonal antibody has been demonstrated in hospitalized patients with COVID-19. In fact, mAbs like bamlanivimab can be linked to poorer clinical outcomes when administered to hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation.
In terms of the safety profile, the adverse effects of mAbs can generally be classified into two different types: those resulting from the action of the antibody, such as opportunistic infections, frequent infections or the development of autoimmune phenomena; and those resulting from the administration of proteins: anaphylactic reactions, cytokine release syndrome, and development of antibodies. In the specific case of bamlanivimab, the most common side effects reported to the FDA were nausea, dizziness, headache, itching, non-severe immediate hypersensitivity, diarrhea, and vomiting.
Bamlanivimab is a new therapeutic tool in the fight against Covid-19 that has been approved in the United States under the heading of Subject to Conditions Emergency approvalThis implies, as is the case in Europe, that it will meet an unmet medical need, provided that the public health benefit of its immediate availability is greater than the uncertainty arising from the limited clinical data available.
However, the drug company responsible for development, Eli Lilly, must commit to providing more clinical data to complement the information on the drug’s efficacy and safety as the results of ongoing clinical trials are available. And only if these data are positive would full and final approval be granted, otherwise the drug would have to be withdrawn from the market.
Bamlanivimab therefore opens a new and promising window in the therapy of Covid-19, unlike other drugs available on the market for other diseases that have shown some effectiveness in this pathology (remdesivir, plitidepsin, dexamethasone, hydroxychloroquine, etc.) this is the first medicine that has been specially developed and approved for the treatment of Covid-19 patients.
The last fight against the virus has begun.
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