Deaths from COVID-19 are often due to the immune system overreacting to the coronavirus. New drugs to suppress this response show promise, researchers say. Westend61 / Getty Images Hide caption
Westend61 / Getty Images
Westend61 / Getty Images
Researchers report some advances in finding drugs that suppress the overwhelming immune response that can kill a patient with COVID-19.
These reactions are triggered by coronavirus infections and can get out of control in some people. It is this response, and not the virus itself, that poses the real danger to people seriously ill with COVID-19.
Doctors realized last year that a cheap and readily available steroid drug is called Dexamethasone can often curb this overreactionwhich is a form of inflammation. In fact, it’s the only COVID-19 drug that clearly saves lives.
“Dexamethasone is a really powerful anti-inflammatory agent,” he says DR. Rajesh Gandhi, an infectious disease doctor at Harvard and Massachusetts General Hospital. But “there are still people who need more.”
Sometimes two anti-inflammatory drugs that are designed to treat rheumatoid arthritis are used, either instead of or in addition to the steroid.
But there is also a race to come up with something more.
Humanigen last week announced in a press release that his drug lenzilumab reduces the risk of someone with COVID-19 having to be put on a ventilator.
“You really don’t want to be in intensive care. You don’t want to be on a ventilator,” says Dr. Cameron Durrant, President and CEO of Humanigen. “You don’t want to be in a hospital bed. That’s why we all strive to offer something that gets patients out of it faster.”
According to Durrant, the company plans to ask the Food and Drug Administration to issue emergency approval for its drug based on a study of about 500 patients.
The press release certainly made an impression on investors who, at least for a short time, drove the company’s share price up sharply. That excitement was tempered when scientists said the press release left some key questions unanswered.
Derek Lowe is a pharmaceutical researcher who writes a related blog called In the pipeline. He noted that there was a wide range of uncertainties about the reported results, which could mean the experimental drug is either much worse or much better than the company reports.
Similar questions came up at NeuroRx announced in a press release that its drug Aviptadil also showed promise in treating an excessive immune response in COVID-19.
These drugs both belong to a class of drugs called monoclonal antibodies. They are designed to deactivate certain molecules that help regulate the immune system. The concept is that by interfering with the molecules that help orchestrate inflammation, the response can be silenced. (The steroid dexamethasone, on the other hand, is less targeted in its ability to contain an immune response.)
Another characteristic of these engineered antibodies is that they are expensive to manufacture, and companies often sell them for thousands of dollars a dose. Therefore, Lowe doubts that these drugs – even if the FDA approves them for emergency use – will replace cheap and readily available steroids as the first drug of choice.
“You would envision that more expensive and more targeted types of anti-inflammatory drugs like this would be the second or third line,” he says. “I think they will help some, but they will not be game changers.”
Vaccines are the cornerstone, and as more people get vaccinated, fewer will end up in the hospital in intensive care.
“It’s a paradox because, in many cases, these are expensive drugs that can be found in wealthy developed countries,” says Lowe. “But the wealthy developed countries will be the ones where a higher percentage of vaccinated people will be vaccinated with fewer patients who will actually need it.”
Another challenge is that these potential products all come to market quickly and have not been tested against each other. Hence it is not clear which one could be better. Mass General’s Gandhi says doctors also need to figure out how best to combine them with other drugs to treat COVID-19 and whether it is safe to do so.
“Many of these anti-inflammatory agents suppress the immune system, so you want to make sure you don’t get any additional side effects when you combine drugs,” he says.
In normal times, questions like this would be studied more slowly and methodically. But these are not normal times. The FDA is accepting less evidence for COVID-19 drugs. The key question is whether the benefits outweigh the risks. Therefore, when these drugs are given emergency approval, there will still be many questions about them.
Gandhi says it’s important to remember that there are also drugs that can keep people with COVID-19 out of the hospital in the first place. These are monoclonal antibodies which are adapted to target and neutralize the coronavirus. They are available nationwide for those at increased risk for hospitalization with COVID-19 and are available free of charge through a government program. But they’re not used as often as they could be.
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