Unknown Risk of DNA Mutation in Merck Covid-19 Vaccine
Some researchers recommend the Merck vaccination pill be restricted to high-risk individuals only since it caused modest amounts of mutations in hamster cells.
According to the University of North Carolina research, the medication only caused modest levels of mutations in hamster cells, prompting some experts to recommend that the treatment be reserved for individuals at high risk.
In a study conducted by Merck and Ridgeback Biotherapeutics, the COVID-19 tablet was shown to decrease the chance of hospitalization by generating mutations in the coronavirus, preventing it from replicating.
Early findings from a clinical study were encouraging. The firms decided to end it early and requested the Food and Medication Administration (FDA) this month for emergency approval to sell the antiviral drug.
However, according to a study conducted by researchers at the University of North Carolina earlier this year, the medication also caused modest amounts of changes in the DNA of hamster cells, raising the possibility that it may pose a small risk of cancer.
"Host risks may not be zero," the authors of a paper published in the Journal of Infectious Diseases stated. "
Researchers from Merck, based in Kenilworth, New Jersey, expressed their opposition to the study in a letter to the journal's editor, claiming that the cell experiments, which were conducted in a lab dish, were not representative of how the drug would affect an entire animal, let alone a human being.
Once this was done, the authors of the UNC paper responded with their own letter, supporting their methodology and asking that the drug's usage be restricted to individuals who are at high risk of severe COVID side effects until additional studies are performed.
The back-and-forth between the scientists is densely packed with technical jargon that defies easy comprehension.
However, there is little doubt that the stakes are very high.
In anticipation of FDA approval of the medication, the United States government has committed to purchase $1.2 billion worth of the tablets. At the cost of about $700 per course of therapy, this will be enough to treat 1.7 million individuals.
Moreover, even as the epidemic enters its second year, hundreds of new patients are admitted to hospitals throughout the United States each week, despite the availability of very effective vaccinations that prevent the majority of hospitalizations.
It was published in Barron's only a few days after Merck announced that the medication, molnupiravir, seemed to decrease the chance of hospitalization and mortality by half.
That conclusion was reached after participating in an international clinical study. High-risk individuals with mild to moderate COVID were randomly assigned to receive the medication or a placebo treatment.
Within 29 days, 14.1 percent of participants who received the placebo were hospitalized or died (53 out of 377 individuals), while only 7.3 percent of volunteers who received the medication (28 out of 385) were hospitalized.
This group did not succumb to their illnesses, leading Anthony Fauci, the nation's top infectious disease expert, to praise the findings as "quite remarkable."
The complete set of data has not yet been made public.
However, additional information, such as the age of study participants and any pre-existing medical problems, will be made public before the FDA takes further action.
None of the volunteers had received any vaccination.
Physicians believe that molnupiravir, if approved for emergency use, would be a helpful weapon against COVID because of the ease with which the oral tablets may be administered.
The intravenous administration of a previously authorized therapy known as remdesivir, on the other hand, is required.
Having the prefix "vir" at the end of both names indicates that they are antivirals, which implies that they are intended to operate by fighting the virus directly rather than by treating patients' symptoms or assisting their immune systems.
Molnupiravir, the medication Merck and Ridgeback Pharmaceuticals developed in Miami, is classified as a nucleoside analogue.
Its molecules are chemical relatives of one of the building blocks of RNA, which is the genetic information contained inside the coronavirus itself.
According to Brianne Barker, a Drew University scientist who studies the immune system's reaction to viruses, the similarity between the molecules allows the molecules to integrate themselves into the viral RNA and induce mutations in the process of doing so.
However, none of these changes would lead the virus to become more contagious or virulent in any way.
The medication produces a more significant scattershot impact, which causes the viral genome to become more infected with mutations in chemical "bases" until the virus cannot replicate itself any longer — a process known as "error catastrophe."
"As the virus continues to reproduce, more and more of the incorrect bases are being produced," she said.
However, in the UNC cell studies, the drug seemed to induce modest amounts of mutation in DNA, which is the genetic code in humans and serves as the foundation for the medication's action.
The question is whether or not the dosage in question represents a genuine threat.
The Merck scientists stated in their letter disputing the UNC research that the hamster cells were exposed to the medicine for 32 days, which was "significantly longer than the 3-to-6-hour exposure period usually utilized per established standards," according to the experts.
Furthermore, the Merck team said that it performed its own tests on lab rats rather than isolated cells and found no evidence that the medicine was responsible for animal DNA changes.
One of the study's authors from the University of North Carolina, Ronald Swanstrom, felt that the medication showed promise.
He is a biochemistry professor at the University of North Carolina in Chapel Hill's medical school. He believes his team's results are merely a sign that further research is required.
In regards to the mutations, he described them as "truly an unknown danger." "It falls between in the middle of being a little danger and being a significant risk."
The results of studies in cells and laboratory animals may not always transfer to human outcomes.
However, the fact remains that there is a small risk that the medication may induce DNA changes in individuals who take it. Therefore, according to him, it may make sense only to administer it to those above a certain age.
They are at greater risk of severe COVID. They are also elderly enough that even a modest amount of mutation would not develop cancer before they die from other reasons, which is why they are considered high-risk.
"I have nothing against them dispensing the medication," he added. "What I'd want to see the FDA demand is that they restrict it to those who might benefit from it," says the author.
The UNC study's author, Barker, who was not engaged in it, felt additional beneficial research. She said that the tests employed by the UNC team were "sensitive," meaning that they were able to identify DNA abnormalities at very low levels — perhaps at levels that were not harmful to the patient's health.
According to her, to be on the safe side, "maybe this implies that we should not utilize this in women of reproductive age."
According to a blog article published earlier this week by Derek Lowe, a pharmaceutical scientist who writes on drug development for Science magazine, the very idea has been made before.
With such limitation in place, "the chemical seems to have the potential to play an important role in the battle against the pandemic," he stated.
As is common in medication trials, pregnant and nursing women were excluded from the Merck study.
Furthermore, women of reproductive age were requested to take contraception or refrain from sexual activity, as did males of all ages in the study.
The research findings are anticipated to be reviewed by an FDA advisory group within a few weeks. The agency's approval may come as soon as that.
Until then, Drs. Lowe and Fauci, among others, remind us that it is preferable to depend on vaccinations and other preventative measures rather than on disease occurrence.
"It reduced the chance of hospitalization and mortality by 50%, which is what this medication achieved," Fauci said on CNN's State of the Union.
"Do you know how to reduce the danger to zero percent? Do you know the way to decrease the risk by 100%? Don't get infected in the first place."
Dr. Anthony Fauci: Merck antiviral Covid drug is an 'important advance.'