- FDA may revise approval path to avoid some procedures abused by pharmaceutical companies
- Bayer terminates $670 million CAR-T partnership with Atara after patient death
- How much do cancer patients pay for CAT-T immunotherapy?
- Highly pathogenic bird flu outbreak: Watch out for ‘super-spreader’ bird species
- CanSino’s COVID-19 vaccine is included in WHO’s emergency use list (EUL)
- Switchable drug and spinal fluid trials may cure Alzheimer’s disease
Alert: Scientists remind Merck of the genotoxic risk of COVID-19 pills
- Unexplained acute hepatitis in children may be related to COVID superantigens
- How long can the patient live after heart stent surgery?
- Keytruda: The 5-year survival rate for advanced lung cancer doubled!
- Amylyx released the latest statistical analysis of new ALS drugs after being opposed by FDA panel last month
- Celine Dion is paralyzed due to muscle cramps: What are Muscle Cramps?
- Taiwan death from COVID-19 vaccination exceeds death from COVID-19
- The world top 5 best-selling drugs in 2020
Alert: Scientists remind Merck of the genotoxic risk of COVID-19 pills.
Last Friday, Merck announced that its antiviral drug molnupiravir (hereinafter referred to as “M drug“) will halve the number of hospitalizations in a trial for high-risk COVID-19 patients. This news sparked heated public opinion.
It seems that people have seen a world in which the treatment of Covi d -19 infection is as simple as swallowing a few pills.
However, some scientists who have studied the drug warn that the method used to kill the new coronavirus is potentially dangerous and may limit the use of the drug.
The principle of action of M drug is to integrate itself into the genetic material of the virus, and then cause a large number of mutations when the virus replicates, effectively killing the virus.
In some laboratory tests, the drug has also been shown to integrate into the genetic material of mammalian cells, causing mutations when these cells replicate.
If this happens in the cells of patients treated with M drugs, it could theoretically lead to cancer or birth defects.
A Merck spokesperson said they conducted extensive tests on animals and the results showed that this was not a problem. “The overall data of these studies show that M drugs are not mutagenic or genotoxic in mammals.” However, scientists who have studied NHC, the active substance of M drug in the body, pointed out that Merck needs to be careful!
“Be careful and at your own risk,” Raymond Schinazi, a professor of pediatrics at Emory University School of Medicine and dean of the Department of Biochemical Pharmacology, has been studying the active substances of M medicine for decades. He reminded him in an email to Barron’s.
Scientists disagree on the severity of this risk. It is really difficult to determine because there is no detailed data from Merck’s animal tests and long-term human safety data.
Safety concerns indicate that the stock market’s reaction to Friday’s positive data from molnupiravir has been overstated. Merck’s (Merck) stock price rose 8.4% on Friday, the COVID-19 pneumonia vaccine maker Moderna’s stock price fell 11.4%, and the stock price of Regeneron, which has developed neutralizing antibodies, fell 5.7%. Shares of Vir BioTechnology, which collaborated with GSK to develop another monoclonal antibody, fell 21.1%.
“This is actually a very subjective idea.” SVB Leerink analyst Dr. Geoffrey Porges said on Friday that investors see Merck’s drug as a panacea for ending the COVID-19 pandemic and will appear in everyone’s medicine cabinet. In fact, this will not happen.
Porges predicts that the FDA will have difficulty answering when it can be used for pregnant women. In his opinion, M drug would be a restricted drug. This restriction refers to the sale and acquisition of M drugs, not to treat them as “controlled substances” under US law like some addictive and illegal drugs.
The M drug was obtained by Merck through a partnership with a private company called Ridgeback Biotherapeutics, which obtained a license for the drug from a non-profit biotechnology company at Emory University.
Professor Schinazi is a professor at Emory University. Although he has not studied M drug, he has studied the active substance of M drug NHC for many years and has written many papers on the compound.
Professor Schinazi is one of the founders of the biotechnology company Pharma Asset. In 2003, he considered developing NHC as a treatment for hepatitis C, but he gave up considering its mutagenicity. Pharmasset later developed the hepatitis C drug sofosbuvir, which Gilead eventually acquired for US$11 billion.
Professor Schinazi told Barron’s that he believes that M drugs should not be used for pregnant women or young people of childbearing age until more data is available. Merck’s M drug trial excluded pregnant women; according to the federal government website that tracks clinical trials, the trial’s scientists asked male participants to “avoid sexual intercourse with the opposite sex” while taking the drug.
In May of this year, Schinazi and scientists from the University of North Carolina published a paper in the Journal of Infectious Diseases, reporting that the NHC caused a mutation in a laboratory test designed to detect mutations in animal cell cultures. “The host’s risk may not be zero,” the author concluded. “Assessing the effectiveness of this drug should be carried out among those who may benefit the most, and monitoring should be provided to assess potential long-term genotoxic side effects.”
Related reading: Genotoxicity? Will the “New Hope of the People” Molnupiravir have this risk?
One of the authors of this paper, Dr. Shuntai Zhou, a scientist at the University of North Carolina’s Swanstrom Laboratory, said that he and his colleagues gave their preliminary findings in July 2020, about a year before his paper was published. Merck & Co.
Shuntai Zhou said, “I am worried that this will lead to long-term mutational effects and even cancer.” “This drug will be incorporated into DNA, and biochemistry will not lie.” Given the various systems that human cells use to limit the effects of mutations, the long-term effects of M drugs are still unknown.
Scientists at Merck responded to the University of North Carolina paper in the subsequent issue of the Journal of Infectious Diseases, saying that their M drug test on animals did not find a higher mutation rate.
It is to question the details of the author’s method of the University of North Carolina. In a reply, scientists at the University of North Carolina believed that M drugs should only be used for high-risk patients with COVID-19 disease until their long-term risks are better understood.
Nathaniel Landau is a professor in the Department of Microbiology at New York University’s Grossman School of Medicine. He has not participated in any research related to the drug. It is very important to prove that there is no cancer.” “Although it looks good in preliminary animal models, it is important not to rush to use it in the clinic, otherwise you cannot be sure that it will not cause cancer even at a very low frequency.”
Drug M first attracted public attention back to May 2020, long before Merck started working with Ridgeback. At the time, the former head of the US government’s Biomedical Advanced Research and Development Administration (BARDA) stated in a complaint that he had been forced to fund M medicine (called E IDD-2801 at the time), but he said Objection, partly because of security considerations. Former BARDA head Dr. Rick Bright told Bloomberg in March this year that Merck’s involvement “melted” his concerns.
Indeed, Merck’s rigorous reputation alleviates the concerns of some observers. SVB Leerink analyst Daina Graybosch pointed out that the M drug data released last week was much later than some investors expected. Graybosch said, “Merck has spent a long time developing this drug. They didn’t say it clearly but I think they have done a lot of work to deal with this risk.”
Graybosch raised its target price on the stock from US$101 to US$104 on Monday. He said, “In the eyes of the public and investors, the continued halo effect of M drug may be more influential than its direct impact on Merck’s income statement.”
Merck said that they conducted two independent experiments on animals, giving animals a higher dose of M drug than the corresponding dose in humans, and for a longer period of time. The results show that M drug is not mutagenic.
In a statement to Barron’s, Merck said: “Patient safety is our company’s common mission and vision: to save and improve lives.” “Our priority is to ensure the safety of patients receiving our medicines and vaccines. . In everything we do—from research and development to the manufacture and distribution of our medicines, vaccines, and other products—safety, quality, and efficacy are our top priorities.”
Merck shares closed up 2.2% on Monday, while Moderna shares fell another 4.5%, and Vir shares fell another 0.8% that day.
Alert: Scientists remind Merck of the genotoxic risk of COVID-19 pills
(source:internet, reference only)