Molnupiravir, an antiviral drug for the treatment of mild to moderate COVID-19, is under review by the FDA for approval.
Merck
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Merck
Molnupiravir, an antiviral drug for the treatment of mild to moderate COVID-19, is under review by the FDA for approval.
Merck
An FDA advisory committee will meet Tuesday to consider whether to recommend a new antiviral drug for the COVID-19 treatment kit.
Medicines taken at home can be a game changer for keeping COVID-19 under control and helping people recover from the early stages of the disease.
“With omicron [variant] neck sigh, we need medicine, we need really effective antiviral drugs and we need more,” Carl Dieffenbach, director of the AIDS Division at the National Institute of Allergy and Infectious Diseases, who is leading the development of antiretroviral drugs.
If approved by the FDA, the new antiviral pill, molnupiravir – produced by pharmaceutical companies Merck and Ridgeback Biotherapeutics – will be the first oral home treatment available for mild to moderate COVID-19. The second antiviral pill, Paxlovid – from the pharmaceutical company Pfizer – is tested by FDA and authorization could be done soon.
Currently, the only FDA-approved treatments for non-hospitalized COVID-19 patients are monoclonal antibodies, often requiring intravenous infusion in the clinical setting. In contrast, pills are cheaper and easier to dispense and take.
“This [could be] huge for the world, in terms of what we can do to slow down and hopefully stop the transmission of this virus,” Dr. Phyllis Tien, an infectious disease specialist at the University of California, San Francisco and a member of COVID-19 Table of treatment instructions for the National Institutes of Health.
Tien and other specialists note that the drug is not used to replace vaccination, but to further support people with the disease, especially the elderly or immunocompromised people, who have not responded. strong response to vaccines.
“You can’t take medicine until you’re sick,” says Dieffenbach. “So you still want to avoid getting this disease. I think that’s the number one rule.”
NPR consulted experts treating COVID-19 for their views on the pill’s promises and pitfalls, and what’s next on the COVID-19 treatment horizon.
How effective are these pills?
According to Merck’s data analysis, molnupiravir reduces risk Hospitalization and death rates in COVID-19 patients are 30%, when the drug is started within five days of symptom onset.
Medical professionals found these results disappointing. “We all want to see higher percentages, but that’s the result,” Dr. Rajesh Gandhi, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School who serves on the COVID-19 Treatment Guidelines Boards for NIH and the Infectious Diseases Society of America.
Oral drug appears to be significantly less effective than monoclonal antibody treatment, reducing risk of severe COVID-19 from 70% to 85%. Given the greater effectiveness of antibody treatments, “I think we’ll continue to use those, especially for those at high risk,” Gandhi said.
Paxlovid, the drug Pfizer, could be much more effective – company has released preliminary results show risk-reducing drugs 89% of hospitalizations and deaths, although these numbers are subject to change once the full study results are analyzed.
Both molnupiravir and Paxlovid are a series of pills taken twice daily for five days. Paxlovid is made with an additional enhancer ritonavir, a medicine that helps keep the medicine working in the body for longer.
How do they work?
When the coronavirus enters a human cell, it makes more copies of itself — more viruses that can spread throughout the body and out of the body to infect others. Both drugs stop the virus from multiplying – by targeting parts of the replication process.
“For the virus to make itself, it first needs to make a very long protein chain,” explains Dieffenbach.
Molnupiravir changes the order of the amino acids that make up proteins, so the proteins fail – and the newly created virus breaks down, unable to infect new cells or replicate itself.
Paxlovid, the Pfizer drug, interferes with the next step of replication – when the virus uses protease – a specific enzyme – to cut the protein chain in precise places to make its building blocks. The drug blocks the enzyme and keeps the virus trapped at this step. “It promotes cell death and activity and generates an amazing immune response,” says Dieffenbach.
Both drugs are intended to help your body fight the COVID-19 infection. “If your viral load drops rapidly, your body doesn’t have to work as much to try to get rid of the virus,” says Tien.
Molnupiravir attenuates the replication of SARS-CoV-2. The drug works by changing the order of amino acids in the proteins it makes to make a new virus, so the proteins are faulty – and the new virus can’t infect or reproduce new cells.
Juan Gaertner / Science Source
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Juan Gaertner / Science Source
Molnupiravir attenuates the replication of SARS-CoV-2. The drug works by changing the order of amino acids in the proteins it makes to make a new virus, so the proteins are faulty – and the new virus can’t infect or reproduce new cells.
Juan Gaertner / Science Source
Are there any known risks or side effects?
Some experts have raised concerns that molnupiravir may interfere in development of infants during pregnancy, or promote growth of new virus variants. At the moment, the safety concerns of this drug are mostly hypothetical, but they are important to weigh the risks of the drug against its benefits, Tien said. She looks forward to a discussion of these potential issues at an FDA advisory committee meeting today.
Because Pfizer works through a different mechanism, concerns about molnupiravir do not directly apply to Paxlovid, although the company has not made its safety data public. Ritonavir, the booster for Paxlovid, is a drug that has been used in the treatment of HIV, and is known to cause nausea, vomiting, and a bitter, metallic taste.
Who will they help?
Both drugs work best when used early in the infection, in patients at high risk for disease progression, says Dr. In clinical trials, both molnupiravir and Paxlovid was given to the patient within five days of symptom onset.
That’s because COVID-19 can be divided into two phases – the viral phase and the immunoregulatory phase. “The goal of the drug is to support the process of actually killing the virus so strongly that the immune system can destroy it,” says Dieffenbach.
In the later stages of the disease, health problems are often turned over-inflammatory – where a person’s own immune response causes many of the symptoms of severe illness. Then, dampening the immune response with drugs such as steroids will be more helpful for recovery.
It would be great to contain the virus, says Gandhi – but there’s a hitch: Because the drug works best when taken within days of infection, testing and treatment is always on. double with each other.
“When someone develops a symptom, they [should be] can do the test and get the results quickly, and if they’re at high risk for advanced disease, start taking the pills,” he said.
Do they work with variations, including omicrons?
Probably. It’s likely that antiviral pills will still be effective against coronavirus variants, says Dieffenbach, even if protection from current vaccines and antibody treatments wears off – although studies are still needed to confirm this, Dieffenbach said.
That’s because antiviral pills target another part of the virus’ life cycle.
Vaccines and monoclonal antibody treatments target the virus through its mutated protein, the protein it uses to attach to and enter cells. Dieffenbach says that this part of the virus is under “strong selection pressure” – new variants of concern, including delta and omicron, often have changes to the mutant protein that could help the virus spread more easily .
Antiviral pills, on the other hand, target the “viral replication machinery,” or the enzymes that help the virus multiply once it’s inside the cell, says Gandhi: “So there’s reason to get lost. It is important that these drugs will continue to be effective against variants including omicrons,” even as immunization-induced immunity declines.
In an email to NPR on Monday, a Merck spokesperson concurred, writing “we believe molnupirvir will likely work against [the omicron variant], “note that the drug” demonstrated consistently effective “on gamma, delta, and mu virus variants.
However, both Dieffenbach and Gandhi say that specific studies are needed to categorize this pill against specific variants to confirm this hunch.
What’s next?
These antiviral pills, if approved by the FDA, could be useful tools, says Dieffenbach – but there is still room for the development of better antiviral drugs. And that was expected: “It wasn’t until we had been on HIV drugs for six or seven or eight years that we really had a cocktail of three drugs that were easier to take and didn’t work. which side is serious,” he said.
Gandhi wanted to see pills that were proven to be safe and effective in specific, vulnerable populations. “I hope for a drug that we can safely give pregnant women, as they are at high risk for severe COVID,” he said. He also wants to see trials for immunocompromised people, who have a longer chance of taking antiretroviral therapy, as they tend to take longer to clear the virus from the system. mine.
Tien said it may be necessary to develop future COVID-19 treatments to stave off drug resistance, should the coronavirus develop to render specific targets ineffective. Once again drawing lessons from HIV treatment, she says, using a combination of therapies can be a strategy against variants.
Even as treatments become better, Gandhi said, they should not be seen as a substitute for vaccines. “What omicron tells me most strongly is that until we reduce COVID rates around the world, these variations will continue,” he said. On treatments: “They’re a backup. They’re a support. They’re not the main way we should get out of this pandemic.”
