Why Monoclonal Antibody COVID Therapy Did Not Meet Expectations

Over the past year, the successful development of highly effective vaccines to prevent SARS-CoV-2 infection has progressed rapidly, but the use of treatments for patients infected with the virus has been delayed. There were many barriers to the use of drugs known as monoclonal antibodies, including logistical challenges and the emergence of new viral variants resistant to some of these antibodies.They are not a cure for COVID, but monoclonal antibodies Effective treatment options This will prevent patients with mild or moderate illness from getting sick and going to the hospital.

Monoclonal antibodies are laboratory-made molecules that mimic the immune system’s response to SARS-CoV-2, targeting specific parts of the “peplomer” protein protruding from the surface of the virus into cells. Prevents binding and tagging to. For destruction. Researchers first isolate antibody-producing B cells from patients who have recovered from COVID. They find the most potent of these antibodies and then produce them in mice manipulated by components of the human immune system.

The use of monoclonal antibodies for the treatment of COVID received national and international attention in October last year when President Trump received an antibody cocktail made by Regeneron after being diagnosed with the disease. Shortly thereafter, the two monoclonal compounds received an Emergency Use Authorization (EUA) from the US FDA and were expected to be an important part of the pandemic response.

However, many factors limit their use. The number of more contagious SARS-CoV-2 mutants is increasing, some of which show reduced sensitivity to monoclonal antibodies. It is also difficult to administer these compounds to outpatients with mild to moderate illness in overwhelming hospitals. Nevertheless, the use of these drugs can delay the illness of some patients at risk of exacerbation and may also help prevent it.

Today, there are several monoclonal antibodies that have been studied and given to the EUA by the FDA. This designation is not a formal approval, but the drug can be used in the event of a public health crisis.First drug using EUA Contains Bamlanivimab (Also known as LY-CoV555 and LY3819253), etesebimab (LY-CoV016 and LY3832479), Casilibimab (formerly REGN10933) and Imdebimab (formerly REGN10987)). In November, the FDA granted EUA to both gamlanivimab and individually Kasilibimab / Imdebimab combinations for use in outpatients with mild to moderate COVID who are at high risk of developing severe illness.

These approvals are based on an interim analysis of two mid-term (Phase II) clinical trials in outpatients with mild to moderate COVID, and these compounds may accelerate viral load reduction in patients. was. However, due to an increase in the number of SARS-CoV-2 variants resistant to gamlanivimab (from about 5% in mid-January 2021 to 20% in mid-March 2021), the FDA issued bumlanivimab on April 16, 2021. Canceled EUA. , And it is no longer available for use as the only treatment for patients. Nonetheless, two monoclonal-combined products (bablanivimab and etesebimab, or casilibimab and imdebimab) are used to treat mild to moderate COVID in unhospitalized patients who are at high risk of developing severe illness or hospitalization. It will continue to be available through EUA. None of these drugs have been shown to be beneficial to more ill inpatients.

the current, NIHCO VID Treatment Guidelines One of two cocktails is recommended for the treatment of outpatients diagnosed with mild to moderate COVID infections who are at high risk of developing severe disease. Treatment criteria include an obesity index of 35 or higher, age 65 or older, diabetes, chronic kidney disease or immunosuppressive disease, or taking immunosuppressive drugs. Some people under the age of 65 are also eligible if they meet certain requirements. Data on the use of these drugs in patients under the age of 18 are limited.

When prescribing these treatments, it is important to start treatment as soon as possible after diagnosis and within 10 days of the onset of symptoms.The· Infectious Diseases Society of America Guidelines Note that the data are stronger for gamlanivimab / etesebimab than for casilibimab / imdebimab. However, they also recommend that prescribers consider which mutants are circulating in the community and whether they are susceptible to monoclonal treatment.

The deployment of monoclonal antibodies took place shortly before the introduction of highly effective vaccines. With the advent of vaccines, monoclonal antibodies are not as widely used as initially thought and are reserved for those who cannot be vaccinated, who do not respond to the vaccine, or who need prevention immediately after significant exposure. I have.

After President Trump was treated with monoclonal antibodies, and after the FDA issued the EUA, the federal government purchased both Bamuramibimab and Casilibimab / Imdebimab more than 500,000 times in anticipation of high demand for these drugs. ..

Not only was the demand from patients weaker than expected, but hospitals and clinics struggled to provide these treatments to patients. There are several explanations for why. Patients may delay seeking treatment until more than 10 days have passed since the onset of symptoms. Test results may be delayed. Logistic problems occur when infusions or injections are given in a location where patients with COVID can be safely examined. Perhaps the biggest barrier during the December-January period was that hospitals were overwhelmed by sick patients and lacked staff to administer these drugs to “not sick enough” patients.

So do I still think these are useful medicines? definitely. Currently, about 60,000 new infections are recorded per day in the United States, many among those who benefit from monoclonal antibody therapy to prevent the progression of serious COVID disease and hospitalization. .. Words about monoclonal antibodies still need to go out. In fact, Regeneron aired an ad during the 2021 Academy Awards in the hope of educating patients about the value of these compounds.

For wider distribution of monoclonal antibodies, the possibility of subcutaneous or intramuscular administration rather than intravenous administration should be considered. We also need to move control from clinics to pharmacies and testing sites to make it easier and easier to implement.

As long as cases of COVID continue, vaccination is not the only strategy implemented for management. Vaccination of high-risk populations is increasing in the United States, but there is a need to increase access to effective treatments that can prevent disease progression, hospitalization, and death in people infected with SARS-CoV-2. there is.

This is an opinion and analysis article.