An experimental cocktail of monoclonal antibodies, REGEN-COV2, has been shown to be a life-saving treatment for some of the most severely affected Covid-19 patients, the results of a clinical trial in the United Kingdom have shown. How important are the results for the management of Covid-19, including in India?
What are monoclonal antibodies?
To fight a viral infection, our body creates proteins called antibodies. Monoclonal antibodies are artificial antibodies that mimic the activity of our immune system. They are produced by a process of extracting specific antibodies from human blood and then cloning them.
These monoclonal antibodies are designed to target a virus or a specific part of a virus – for example, REGEN-COV2 is a cocktail of two monoclonal antibodies developed to target the SARS-CoV-2 spike protein. Monoclonal antibodies bind to specific parts of the spike protein, blocking its ability to infect healthy cells.
In addition to Covid-19, monoclonal antibodies have been used in the treatment of cancers as well as Ebola and HIV.
What is their importance in the treatment of Covid-19?
Research during the pandemic has heightened optimism about the ability of monoclonal antibodies to help reduce the risk of hospitalization. Some monoclonal antibodies have been shown to be able to retain activity against several variants of the virus, suggested Dr.Anthony Fauci, chief medical adviser to the US president and director of the US National Institute of Allergy and Infectious Diseases, at a briefing at the White House on June 3. .
Although they are a crucial and promising part of treatment, monoclonal antibodies also have limitations. So far, these therapies have been most successful in high-risk groups with mild to moderate Covid-19. They are not approved for use in people hospitalized with severe Covid-19 and those requiring oxygen.
Delivering them to the “right patients at the right time” is very important for the greatest benefits, especially in resource-constrained environments, according to Dr D Behera, Padma Shri and former division head of PGIMER’s Respiratory Department. Chandigarh.
Some emerging variants like the ‘variant of interest’ Delta Plus have also shown the ability to override the use of monoclonal antibodies, according to Dr. VK Paul, NITI Aayog health member and chair of the National Expert Panel. on the administration of vaccines against Covid-19.
What does the new study show?
The University of Oxford said last week that its RECOVERY trials found that for hospitalized patients with severe Covid-19 “who have not developed their own natural immune response,” the cocktail of monoclonal antibodies from Regeneron reduced the risk of death by a fifth compared to those who had received standard care. “So for 100 of those patients treated with the combination of antibodies, there would be six fewer deaths,” the university said in a statement.
The therapy reduced hospital stays by four days for patients lacking their own natural immune response. It also reduced their risk of needing a ventilator. However, “no such benefit was observed in the overall study population”, which includes patients who may have developed a natural antibody response.
These results essentially mean that the therapy would be more beneficial for those who have not been able to develop their own antibody response, even if they have developed severe symptoms or have been hospitalized.
With 9,785 participants between September 2020 and May 2021, this is the first trial large enough to determine “definitively” whether this treatment reduces mortality in hospitalized patients with severe Covid-19. This is important, given that this therapy has so far only been approved for mild to moderate Covid patients.
Is this therapy available in India?
REGEN-COV2 is available in India thanks to a partnership between the Swiss pharmaceutical giant Roche and the Indian company Cipla. The therapy, a combination of monoclonal antibodies casirivimab and imdevimab, had received restricted emergency use approval from the Central Drugs Standard Control Organization in May.
In early June, another antibody cocktail therapy – Eli Lilly’s bamlanivimab and etesevimab – received similar emergency approval.
Both cocktails of antibodies are indicated for use in people with mild to moderate Covid-19 who do not need oxygen and are at high risk of progressing to serious illness.
GlaxoSmithKline, which on May 26 announced the US FDA’s emergency use approval for Sotrivimab, is exploring options to make monoclonal antibody therapy available for India.
In India, Zydus Cadila plans to take an antibody cocktail, ZRC-3308, in trials.
Is it expensive?
Such therapies are expensive because they are difficult to perform and take a long time. In India, Cipla supplies 100,000 packs of REGEN-COV2 at a maximum retail price of around Rs 1.20 lakh per pack. With a pack offering a treatment for two patients, the price of a dose for one patient is Rs 59,750, all taxes included.
Eli Lilly is engaged in an “active dialogue” with the Indian government to “donate” his cocktail of antibodies to Covid-19 patients.
Monoclonal antibodies must be made in tissue culture, said Dr Arturo Casadevall, chair of the Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. “You have to grow the cells. And those cells have to produce the protein which then has to be purified, ”Dr Casadevall said in the school’s“ Public Health on Call ”podcast on Nov. 2.
How do monoclonal antibodies compare to convalescent plasma therapy?
Last month, India abandoned the use of convalescent plasma as an ‘off-label’ option from its Covid-19 treatment guidelines. Over the past eight months, evidence from trials has shown that it does not have significant benefits in improving patient outcomes.
Compared to plasma, scientists have expressed more confidence in the promise of monoclonal antibodies. The two antibody therapies, they differ in the way they are made.
Convalescent plasma therapy involves delivering antibodies from plasma recovered from a Covid-19 patient. This means that those who receive this therapy will get all the antibodies that the recovered patient has made.
Monoclonal antibodies are the process of taking a specific antibody and mass-producing it in a factory. For antibody cocktails, you provide a combination of two or more of these antibodies.
Monoclonal antibodies are “extremely pure” due to their homogeneous nature, Dr. Fauci told MedPage Today in August. “The difference between monoclonal antibodies and convalescent plasma is (that) the plasma contains a lot of other things, which could lead to allergic and other reactions,” Fauci said. Data from clinical trials of monoclonal antibodies at the time indicated that it was a “very promising form of prevention and treatment,” Dr Fauci said.