MSD Anti-Covid Pill May Be Risk to Pregnant Women

A new anti-Covid pill by MSD drugmaker (known as Merck in the US and Canada) has raised hopes of transforming the landscape of treatment options for Americans at risk of becoming seriously ill from Covid, at a time when the omicron variant of the coronavirus has been multiplying the cases of the disease in European countries with a high rate of vaccination.

But two weeks after a committee of experts at the Food and Drug Administration (FDA) narrowly approved the authorization to use the drug, known as molnupiravir, the FDA is still analyzing the request for approval. One of the biggest unknowns facing regulators is whether the drug has the potential to mutate human DNA while wreaking havoc on the virus’s genes.

Scientists are especially concerned about pregnant women because the drug can affect dividing fetal cells, theoretically causing birth defects. Members of the FDA’s expert committee voiced this same concern at a November 30 public meeting.

“Do we want to reduce the risk to the mother by 30% but at the same time expose the embryo and fetus to a much greater risk from this drug?” asked Dr. James Hildreth, director of Meharry Medical College, at the meeting. Tennessee. “My answer is ‘no’. Under no circumstances would I advise a pregnant woman to take this medication.”

FDA advisers also noted that the risks could extend to other patients, including men who want to become fathers, although these risks are still poorly understood and MSD said its own studies have not provided evidence that molnupiravor cause mutations in the DNA.

Crucially, mulnupiravir is expected to work against omicron. But the drug is viewed with concern by some scientists and regulators in Europe for being less effective than certain other treatments: it has been shown to reduce the risk of hospitalization and death by 30% if given within five days of symptoms appearing. .

See what scientists already know about how mulnupirovir works and its potential risks.

How does molnupirvir work?

When the drug is processed in the body, it creates compounds very similar to the building blocks of RNA, the genetic material present in the coronavirus.

This creates problems for the coronavirus as it copies itself: once the virus enters a cell and begins to replicate, the drug compound can penetrate the virus’s RNA and insert enough errors to make the virus impossible to survive.

“Molnupirvir disguises itself,” explained Elizabeth Campbell of Rockefeller University. Specialist in structural biology, she studies coronavirus antivirals. “It can propagate errors that will spread throughout the genome.”

By making more and more mistakes, the virus eventually stops, Campbell said. This helps the body fight the infection, potentially saving the patient’s life.

The problem is that the same compound that interferes with the replication of the virus’s genetic material can also be turned into something that resembles one of the fundamental elements of DNA. Some scientists fear that this could cause errors in the patient’s own DNA or that of a developing fetus.

“If the cells are replicating, it means they are adopting a version of one of the key DNA elements derived from molnupirvir and incorporating it,” Campbell said.

How serious is this a problem?

A team of researchers at the University of North Carolina studied the use of molnupirvir in isolated hamster cells for 32 days and found that the drug actually causes DNA mutations.

These mutations could “contribute to the development of cancer or cause birth defects in a developing fetus or by incorporation into sperm precursor cells,” the study authors wrote.

The drug only attacks dividing cells, which are relatively few in adults. This poses a more restricted risk than other mutagenic agents, such as radiation, which can damage DNA in all types of cells.

Still, Ronald Swanstrom, an HIV researcher at the University of North Carolina at Chapel Hill and co-director of the hamster cell study, said adults have enough dividing cells — for example, in bones and intestinal epithelium — to cause concern. He also pointed out that men constantly produce dividing sperm cells that may carry potential mutations.

“I don’t think anyone knows what this dose means in terms of human outcomes,” Swanstrom said. “I hope it’s trivial, but I don’t think anyone knows.”

In a letter objecting to Swanstrom’s findings, MSD scientists said the hamster cells were exposed to molnupirvir for a considerably longer period than would be the case in patients with Covid. The company said it tested the drug on rodents and found no signs of DNA mutations (or mutagenicity).

“We believe that this molecule carries a very low risk of mutagenicity,” Dr. Roy Barnes, MD, MD, said in an interview. “This drug is used for five days and the goal is to eradicate the virus quickly. It is not a long-term treatment.”

Biologist Brianne Barker of Drew University said MSD should publish its data obtained from rodents, but the fact that the treatment is short-lived reduces the risks. She also said that isolated hamster cells are “a little different from what is actually found in an organism”, making it difficult to know how serious the dangers to humans would be.

What are the risks during pregnancy?

Cells in the fetus are constantly dividing, increasing the risk of mutations. For this reason, MSD excluded pregnant women, nursing mothers, and women who were likely to become pregnant from its clinical trial.

“Human development in utero is a simply amazing sequence of events,” said infectious disease expert Dr. John Mellors of the University of Pittsburgh Medical Center. “If you start interfering with it in any way, it could end up wreaking havoc.”

Mellors noted that, according to MSD information, high doses of molnupiravir given to pregnant rats could cause developmental abnormalities or fetal death.

Scientists say older antiviral pills hold lessons for the safe prescription of molnupirvir. Before the arrival of potent hepatitis C medications in recent years, doctors often used a drug known as ribavirin as part of a combination treatment of patients with hepatitis C.

“If you read the package insert, you’re definitely going to think about it,” said Dr. Ashwin Balagopal, a Johns Hopkins University researcher who has treated hepatitis C patients with ribavirin and is now directing a study of molnupiravir. “We were careful, but we didn’t avoid using the drug because we thought ‘let’s hope something better comes along’.”

How are scientists weighing the benefits and risks of molnupirvir?

Pfizer is expected to receive government clearance in a matter of weeks for its own anti-Covid pill, which appears to be more effective than MSD’s — and does not carry the risk of mutating human DNA.

But molnupiravir is expected to be more readily available than Pfizer’s drug in the coming months, when the United States could face another large outbreak of cases caused by the omicron variant.

“We have to do what we can with what we have at hand right now,” said Balagopal.

As people age or develop health conditions that put them at greater risk of becoming seriously ill if they become infected with the coronavirus, the benefits of molnupiravir may outweigh the risks, scientists said. Barker noted that adults readily accept the increased risk of mutations from sunbathing, for example.

“In particularly high-risk individuals who contract Covid, that risk may outweigh that of mutagenesis,” she said. “But a younger person who is planning to have children or who is pregnant may want to take a different drug.”

Translation by Clara Allain.