The first oral drug for COVID-19 was Effective Against Multiple Variants

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The first oral drug for COVID-19 was Effective Against Multiple Variants

The first oral drug for COVID-19 was Effective Against Multiple Variants.

The world’s first oral drug for COVID-19 was approved, effective against multiple mutant strains.

On November 4th, the British Medicines and Healthcare Products Regulatory Agency ( MHRA) approved the world’s first anti-coronavirus oral drug Molnupiravir (hereinafter translated as Molnupiravir) to be marketed in the country.

According to the MHRA announcement, the drug will be used in patients with mild to moderate COVID-19 disease who are hospitalized over 18 years of age or at a higher risk of severe illness. The so-called “high risk” means that it has at least one risk factor that easily develops into a serious illness, such as obesity/overweight, advanced age (>60 years) , diabetes or cardiovascular disease, etc.

The medicine needs to be taken orally twice a day, 4 capsules each time, taking 5 days as a course of treatment. Studies have shown that taking the drug within 5 days after the COVID-19 test is positive and symptoms appear, the patient’s risk of hospitalization or death will be halved.

The first oral drug for COVID-19 was Effective Against Multiple Variants.

Effective against multiple mutants

Molnupiravir was jointly developed by Merck and Ridgeback Biotechnology.

According to the “In-Depth Interpretation｜The first oral drug for the COVID-19 is here, what impact will it have on the epidemic?” 》 (Click on the title to learn more) . It is active against a variety of RNA viruses, including the new coronavirus, and can cause false mutations in the virus, thereby interfering with virus replication and achieving antiviral effects.

Judging from the MHRA announcement, Molnupiravir was approved for listing in the country, mainly based on the interim analysis results of the phase III clinical study MOVe-OUT released by Merck on October 1 this year. The study was originally planned to recruit 1,550 unvaccinated patients with COVID-19s. Due to the gratifying data in the previous period, the study terminated the recruitment early.

The interim analysis showed positive results in 2 areas:

First, the risk of hospitalization and death in the medication group was halved.

29 days after 775 subjects were randomized, the hospitalization or mortality of Molnupiravir group and control group were 7.3% (28/385) and 14.1% (53/377) (p=0.0012), respectively . A total of 8 subjects died, all in the control group. Based on this, the researchers believe that Molnupiravir can reduce the chance of mild to moderate patients progressing to severe illness or death by 50%, and reduce the mortality rate to 0%.

Second, it is effective against mutant strains.

About 40% of subjects received virus sequencing. The results showed that Molnupiravir showed consistent efficacy in the mutant strains Delta, Gamma and Mu.

“Genotoxicity” question not answered

“Based on the MOVe-OUT analysis, the safety of the Molnupiravir group and the control group are equivalent, and there is no statistical difference in the probability of adverse drug events.” Albert Shaw, an infectious disease expert at Yale University School of Medicine, said in a post, but in the middle of phase III The analysis was released within one month of the market, which could not answer the long-term safety issues of the drug.

The process of artificially increasing the mutation rate of the virus until it can no longer replicate and eventually disappears is called lethal mutation. Like Molnupiravir, those that permanently change the genetic information of the virus’s RNA by inserting an error code into it are called mutagenic agents. In May of this year, the American Journal of Infectious Diseases published a study by the University of North Carolina that mutagenic agents may have teratogenic effects on human genes. This may induce cancer, may also affect fetal development and increase the incidence of birth defects.

Rick Bright, former head of the U.S. Biomedical Advanced Research and Development Administration (BARDA) , said that in an animal drug experiment similar to Molnupiravir, his offspring were found to have no teeth at birth or part of their skulls missing. In April 2020, due to concerns about mutagenicity, Rick Bright, who was still in office, refused to fund the development of Molnupiravir.

The British MHRA stated that the above-mentioned “genotoxicity” problem has been extensively studied and has not been found to pose a risk to humans. Animal experiments did not find that Molnupiravir has gene mutagenesis or toxicity, so it was able to enter Phase III clinical.

But Jaimie Meyer, an infectious disease expert at Yale University School of Medicine, pointed out that the MOVe-OUT study did not include women who are pregnant, breastfeeding, or trying to become pregnant. Both men and women were required to take contraceptive measures and could not have unprotected sex within 1 week after taking the drug. “Drugs move from clinical trials to the market, and long-term safety issues will be particularly important.”

Can oral drugs end the epidemic?

Molnupiravir was approved and was regarded as the “new dawn of anti-epidemic”. Its oral administration method will greatly improve patient compliance and convenience. The home isolation treatment can also reduce the workload of the hospital and help avoid medical runs.

However, some comments pointed out that this may lead to a new round of pandemic.

First of all, timely and effective distribution of drugs is a problem.

The applicable population of Molnupiravir is more limited. Except for mild to moderate symptoms and at least one high-risk factor, the earlier the drug is used, the better the effect. MHRA recommends that the medication should be taken as soon as possible within 5 days of the onset of symptoms after a positive test.

This point in time is extremely important. An earlier clinical study of patients with Wuhan Covid-19 showed that the average time for an infected person to progress from mild illness to dyspnea is 5 days.

However, in most countries, virus testing is not a “compulsory act.” The people conduct self-tests based on their own conditions and at home. This may cause the patient to miss the optimal medication time.

Secondly, when patients with mild and moderate illnesses are treated at home, their mobility may increase or lead to more spread of the virus.

The doctor prescribes the drug to eligible patients, and the patients can leave without being hospitalized and isolated. In July, India announced the research data of Molnupiravir, claiming that 78.3% of mild patients had a negative nucleic acid with a 5-day treatment course and 28-day observation period. That means that within a period of time, positive patients may spread the virus out when they are free to move around. The newly infected patients will also prescribe drugs, move freely, and spread the virus.

US Cable News Network (CNN) reported that the oral antiviral medication may be a “game changer.” But in the early days of drug supply, this was just a “game” for a few countries.

Merck said it will produce 10 million courses of Molnupiravir by the end of this year.

Up to now, the U.S. government has ordered 1.2 billion U.S. dollars, or about 1.7 million courses of drugs. At the same time, at least eight countries or regions in the Asia-Pacific region, including New Zealand, Australia and South Korea, have signed agreements or are negotiating procurement. Among them, Australia confirmed the purchase of 300,000 treatment courses.

As of October, the UK has purchased 480,000 courses of related drugs. The British government and the British National Medical Service System (NHS) will confirm how to configure and use it during the course of treatment. Independent drug analyst Penny Ward told the British Medical Journal that according to the current average daily rate of more than 40,000 infections in the UK, it will soon run out.

“What we worry most is that, just like the distribution of the COVID-19 vaccine, rich countries get a share that far exceeds their population. Low-income and middle-income countries are once again at a disadvantage.” CNN said.

On October 27th, Merck and its partner Ridgeback announced that they have reached a treatment license agreement with the United Nations to give up patents in 105 low- and middle-income countries around the world to allow them to produce generic drugs.

Merck also said that it plans to adopt a tiered pricing strategy for developing countries. According to a draft document disclosed by Reuters, the World Health Organization (WHO) is working to provide low-income countries with access to treatment at a price of US$10 per course of treatment.

The first oral drug for COVID-19 was Effective Against Multiple Variants.

Reference: The first oral drug for COVID-19 was Effective Against Multiple Variants

1.Merck and Ridgeback’s Molnupiravir, an Oral COVID-19 Antiviral Medicine, Receives First Authorization in the World. Merck

2.Covid-19: UK becomes first country to authorise antiviral molnupiravir. BMJ. 2021; 375. doi.org/10.1136/bmj.n2697

3.Countries in Asia are placing orders for a new drug to treat coronavirus. Poorer nations could miss out again. CNN

4.Molnupiravir: The Game-Changing Antiviral Pill for COVID-19?. John Hopkins Bloomberg School of Public Health

5.9 Things You Need To Know About the New COVID-19 Pill. Yale Medicine

6. COVID-19 oral medicine is coming soon? In the fourth quarter, focus on these 4 companies for Phase 3 clinical unblinding | See Zhi Institute. Wall Street Insights

7.Molnupiravir: long-term safety questions linger as approvals approach. pharmaceutical technology

8.β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells. The Journal of Infectious Diseases. Volume 224, Issue 3, 1 August 2021, Pages 415–419. doi.org/10.1093/infdis/jiab247

(source:internet, reference only)

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