By Rebecca Aicheler, Senior Lecturer in Immunology, Cardiff Metropolitan University
Cardiff (UK): A new treatment could soon help protect people from developing severe COVID. AstraZeneca has just released results from a phase 3 clinical trial the final stage of testing before a drug is authorised that suggest its new COVID treatment, AZD7442 is effective at reducing severe disease or death in non-hospitalised COVID patients.
The treatment contains antibodies, which are usually produced naturally in response to a COVID infection or vaccination. They work by recognising specific parts of SARS-CoV-2 the virus that causes COVID and either attack these directly or bind to them to stop the virus from working and flag it for destruction by other parts of the immune system.
After they’ve done their job of clearing the virus, the antibodies remain in the body for a period of time, making up part of our immunological memory. If what they target is encountered again, they can leap into action.
The new treatment, AZD7442, uses special antibodies called monoclonal antibodies. These are antibodies produced in a lab that imitate the body’s natural defences in this case mimicking the immune system’s response to COVID.
Artificially developing antibodies to fight disease isn’t a new technique. This technology is already used to treat many diseases, including leukaemia, breast cancer and lupus. In fact, this isn’t even the first time the technique has been used for COVID. The first COVID monoclonal antibody treatment was approved in the UK in August 2021.
How does AstraZeneca’s treatment work?
AZD7442 is a cocktail of two monoclonal antibodies tixagevimab and cilgavimab that are designed to reduce the severity of a SARS-CoV-2 infection and so prevent people from getting severely ill.
Both of these antibodies bind to different parts of the virus’s spike proteins, which cover its outer surface and are what the virus uses to infect cells. It’s thought that attaching to these proteins is what gives the medicine its effect, as this stops the virus from being able to get inside cells and reproduce.
The two monoclonal antibodies in the cocktail are based on antibodies taken from patients who survived COVID. Scientists at AstraZeneca took blood samples from patients and isolated immune cells called B cells, which are the antibody factories of the human body. They then grew more of these B cells in the lab and used them to make large quantities of the two antibodies, which they had identified as specifically targeting the coronavirus’s spike protein.
But the key difference between this and other antibody-based treatments is that in AZD7442, the antibodies have been modified so they stay in the body for longer.
Studies using similarly modified antibodies against another respiratory virus respiratory syncytial virus have shown that this approach gives long-term protection, with the modified antibodies having triple the durability of conventional antibodies. It’s hoped that a single dose of AZD7442 could offer 12 to 18 months of protection from severe COVID, though we’ll have to wait to see exactly how long protection lasts.
How well does it work?
AstraZeneca’s phase 3 trial investigated the effectiveness of the treatment when given to patients who were infected with SARS-CoV-2.
The study looked at 822 participants who were over the age of 18. Only around 13% were 65 years and over, but 90% had health conditions that put them at high risk of severe COVID, such as cancer, diabetes, obesity, chronic lung disease or asthma, cardiovascular disease or a weakened immune system.
The trial results show that of the 407 people who received AZD7442, 18 developed severe COVID or died, compared with 37 of the 415 people who received a placebo. This suggests that those in the AZD7442 group were 50% less likely to develop severe COVID than those taking a placebo.
The trial also looked specifically at patients who received treatment quickly that is, within five days of their symptoms starting. In this group, AZD7442 reduced the risk of severe disease or death by 67%, suggesting that early treatment with AZD7442 provides greater protection.
It’s important to note, however, that these results have been released by AstraZeneca but don’t yet appear to have been formally reviewed by other scientists. So any findings need to be treated with caution.
How useful will it be?
These results suggest that AZD7442 could be a valuable tool for patients in need of instant immunity against COVID, such as those who have not responded to vaccines because of a weakened immune system or those in other high-risk groups.
However, more detail of the characteristics of the patients who did and did not benefit from the medicine is required to fully understand who will benefit most from receiving this drug.
And when considering how useful AZD7442 could be, it’s important to consider when in the course of the disease the treatment will be given. For many, severe disease with COVID isn’t caused by the virus replicating, but by the immune system going awry.
This means that to prevent severe disease, drugs such as AZD7442 need to be given early in infection before the overzealous immune response kicks in. Give them too late, and treatments like this that target the virus directly are unlikely to offer many benefits (unlike those that can control inflammation and immune overreaction, such as dexamethasone or tocilizumab).
But one thing that could help the treatment be deployed early during infection is the fact that it only needs to be injected into a muscle, rather than be given intravenously. This means it can be given at a clinic, without patients needing to come into the hospital.
However, monoclonal antibody treatments are notoriously expensive, and the cost of AZD7442 has not yet been released. This could be the biggest barrier to the drug having a big impact worldwide assuming, of course, that its phase 3 results pass the scrutiny of regulators and the drug is approved. (The Conversation)
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