Regeneron: Not a panacea


In early October 2020, then-US President Donald Trump contracted in Corona. Shortly after diagnosis He was treated with a drug called REGEN-COV2 (later the number 2 was removed from the name of the drug), which was then an experimental treatment that had not yet received the approval of the health authorities in the country. There are good reasons to believe that the treatment did help Trump deal with the disease successfully and recover easily and quickly.

Since then, the treatment has been received from the Food and Drug Administration (FDA) in the United States Permission for emergency use For the treatment of mild corona patients who are at high risk of degenerating into a serious condition, as well as for high-risk people living in the same home with a verified patient. The drug is essential to receive within a few days from the moment of diagnosis. It is not intended for patients who already need extra oxygen, as at this stage the drug is ineffective.

What does the drug do?

Antibodies are proteins thatThe immune system produces In order to identify foreign elements that have invaded the body and cling to them. For example, most of the antibodies to the coronary virus (SARS-COV-2) are adapted to detect very small parts of one of the envelope proteins in the virus, called “spike”. Some antibodies only mark the invader and thus make it easier for the immune system cells to recognize it and destroy it. Others cling to the virus in a place that interferes with its proper functioning, so they are called neutralizing antibodies.

The drug REGEN-COV, By Regeneron, includes two antibodies that neutralize corona spike protein. The antibodies, called Casirivimab and Imdevimab, attach to the region in the spike protein through which the virus enters our body cells. By doing so, they prevent the virus from taking over the cell’s mechanisms and multiplying. These two antibodies Selected from a database Of about two hundred different antibodies detected in the blood of corona patients.

Efficiency close to infection

Treatment is given as part of clinical trials by intravenous infusion. It is given to patients aged 18 and over who have been infected with corona and are in one of the risk groups that are relatively likely to develop a serious illness. Phases 1 and 2 of the trial, designed to test the drug’s safety and its ability to elicit the desired biological response, were performed on 275 mild patients, and their findings were published in the New England Journal of Medicine. The final phase (Phase 3), whose role is to test the drug’s effectiveness, was conducted on about 4,000 mild patients and its findings Published in the article archive medRxiv, And have not yet undergone professional control as usual.

The study found that the drug was 71 percent effective in preventing serious illness and mortality, when given to non-hospitalized patients within less than 72 hours of the onset of symptoms. In addition, patients experienced relief of corona symptoms four days on average before the control group of patients who did not receive the drug and who did not develop a serious illness.

A follow-up study by Regeneron, S.Also published inNew England Journal of Medicine Examine the effectiveness of the drug in preventing infection or the appearance of symptoms in family members aged 12 and over who live in the same home with a diagnosed corona patient. In this case the drug was given by subcutaneous injection, rather than by infusion – a much easier and less invasive method. Approximately 1,500 subjects whose family member was diagnosed with corona up to four days before the study, but who themselves were found to be negative on corona testing, were divided into a group that received the drug and a control group that did not receive it. The study found 66 percent efficacy in preventing infection and 81 percent in preventing symptomatic disease. Among those who nevertheless occurred, the symptoms of those who received the drug passed within a median time of about ten days, compared with three weeks in the control group.

Parallel research Conducted on about two hundred asymptomatic patients, found that a subcutaneous injection of the drug reduced by a third the proportion of patients who eventually developed symptoms – 29 percent, compared with 42 percent of all verified in the control group. In addition, the drug shortened the duration of symptoms by five and a half days compared to the control group, and prevented deterioration to severe disease in all recipients of the drug.

Efficacy for patients in critical condition

Treatment therefore seems to be helpful when given in the very early stages of dealing with the disease. What about patients whose condition has already deteriorated?

Researchers from Toulan University in New Orleans reported bNewspaper Viruses About a patient with lymphoma (leukemia) infected with corona. For nine months he was hospitalized in a mild-moderate condition in them and no treatment benefited him. Finally when he received REGEN-COV he recovered from the virus.

In contrast, a study conducted at the University of Oxford in the UK found that the drug is almost ineffective for patients who are already hospitalized. The study, Published in the MedRxiv article archive, examined about ten thousand hospitalized patients the effect of the drug on the development of the need for assistance of the respirator and mortality from the disease. The researchers found that the drug reduced mortality from 30 percent to 24 percent, but only in inpatients who had not yet developed antibodies to the virus in their bodies. Among patients who had already developed their own antibodies, there was no difference in mortality, nor was there a significant difference in disease exacerbation between the treatment group and the control. It follows that the drug is effective only in the first days of the disease, especially before the body has developed antibodies and before there has been a significant deterioration in respiration.

The research data show that the antibodies given by injection are absorbed into the bloodstream and their concentration reaches a peak about a week later, so an infusion provides a faster response than the administration of the antibodies by injection. In both methods, the levels of antibodies in the blood remain high over time, and the level of antibodies in the blood drops to half the initial amount only about a month later.

Also, almost no side effects of the drug were found, other than an allergic reaction or a side effect of giving the infusion itself, such as local bleeding, swelling, or infection. In addition, the company notes that in some cases patients’ coronary symptoms worsened as a result of treatment, but it is unclear whether this is related to the administration of the drug or the course of the disease.

Durability of new variants

Like the corona vaccines, the drug was developed on the basis of antibodies that act on the spike protein of the original corona virus. In the meantime, however, the virus has accumulated changes (mutations), and since July 2021 Raging in Israel Variant deltaOf the virus, the characteristics of which are slightly different from those of the original virus. Is the drug still effective against it as well?

Virologist Olivia Schwartz of the Pasteur Research Institute in France studied with his research group the efficacy of several antibodies, including caziribimab and imadbimab, by neutralizing some of the variants of the virus. Findings of the study, Q.Published in the journal Nature, Showed that caziribimab is not effective against the beta variant (the variant discovered in South Africa), but acts at the same level of efficacy against the original virus, the alpha (British) and delta variant. Imadbimab is also effective against beta. Thus, the drug appears to be approximately as effective against the Delta variant as it is against the original virus.

The Regeneron website states that the drug Also effective against newer variants Such as Epsilon, Kappa and Lemda. A new variant, called C.1.2, Also contains the mutations of beta and therefore may impair the effectiveness of the drug against it – although no data have yet been published confirming that this is indeed the case. The research of Schwartz and colleagues, as well as company data, is based on cell cultures only, so care should be taken not to draw too sweeping conclusions from them, although it is likely but not certain that the drug will work similarly within the human body.

One of the concerns about antibody treatments is that antibody-resistant variants will develop during them. To test this, the company compared treatment with single antibodies to a combination of two or three antibodies between the two antibodies in the drug. BA study published in the journal Cell, They showed that while the use of a single monoclonal antibody encourages the emergence of resistant variants in cell cultures and blood of laboratory animals, a combination of two antibodies in the drug prevented the appearance of a similar process in cell and blood cultures of laboratory animals and humans. Therefore, they state that the risk of developing drug-resistant viruses is very low.

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Save hospitalizations and suffering

If so, according to studies published so far, the position of physicians calling for more widespread use of the drug seems to be a justified position. The cost of treatment, which is estimated according to Press releases In Israel, about $ 1,500 per use, lower than the cost of prolonged hospitalization due to a serious illness, and will also save those infected weeks or months of suffering during hospitalization and subsequent rehabilitation and reduce mortality. Giving the drug to people in risk groups who spend a long time with a verified patient will prevent many of them from getting sick, and will slow down the spread of the plague.

The use of the drug in the United States is steadily rising and according to An article published in mid-August on the Bloomberg website, Its use has expanded within a few weeks from several thousand servings per week to more than one hundred thousand. A model published in the archive medRxiv It was estimated that if the drug had been given to half of the patient families in the United States who are 50 or older who are not vaccinated, they would have avoided about 1,800 symptomatic patients, over 500 hospitalizations, 83 deaths and spending about $ 3 million on the health care system. Extensive use of the drug will also help to learn about its efficacy and safety based on large numbers of patients, including those who have already been vaccinated – information that is still lacking.

 

However, it is important to remember that a drug is not a substitute for a vaccine and that it is always better to prevent the onset of a disease in the first place than to treat it after you have already been infected. Regeneron also emphasizes this in its publications. The vaccine is a long-term preventative treatment, which protects very highly from severe morbidity and death from all the variants known today.

The drug is effective only if given in a short period of time from the onset of symptoms or exposure, but is almost useless after the patient’s condition has deteriorated. In addition, the drug is less effective against the beta variant and the like. The US Food and Drug Administration (FDA)’s approval to use the drug is limited to people who are at high risk of experiencing severe symptoms of the disease. Therefore those who are not in the risk group will not receive the drug, although even low-risk people, and even children, may become seriously ill and die if not vaccinated.

By Editor

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