Merck says research shows its Covid-19 pill works against variants

[steveluv]

https://www.straitstimes.com/world/united-states/merck-says-research-shows-its-covid-19-pill-works-against-variants

Merck says research shows its Covid-19 pill works against variants

Molnupiravir instead targets the viral polymerase, an enzyme needed for the virus to make copies of itself.PHOTO: REUTERS

WASHINGTON (REUTERS) - Laboratory studies show that Merck & Co's experimental oral Covid-19 antiviral drug, molnupiravir, is likely to be effective against known variants of the coronavirus, including the dominant, highly transmissible Delta, the company said on Wednesday (Sept 29).

Since molnupiravir does not target the spike protein of the virus - the target of all current Covid-19 vaccines - which defines the differences between the variants, the drug should be equally effective as the virus continues to evolve, said Jay Grobler, head of infectious disease and vaccines at Merck.

Molnupiravir instead targets the viral polymerase, an enzyme needed for the virus to make copies of itself. It is designed to work by introducing errors into the genetic code of the virus.

Data shows that the drug is most effective when given early in the course of infection, Merck said.

The US drugmaker tested its antiviral against nasal swab samples taken from participants in early trials of the drug.

Delta was not in wide circulation at the time of those trials, but molnupiravir was tested against lab samples of the variant behind the latest surge in Covid-19 hospitalisations and deaths.

Merck said earlier this year that a small, mid-stage trial found that after five days of molnupiravir treatment, none of the patients taking various doses of the drug tested positive for infectious virus, while 24 per cent of placebo patients did have detectable levels.

Merck is currently conducting two Phase III trials of the antiviral it is developing with Ridgeback Biotherapeutics - one for treatment of Covid-19 and another as a preventive.

Merck anticipates that the Phase III treatment study will finish in early November, Grobler said.

The trial enrolled non-hospitalised Covid-19 patients who have had symptoms for no more than five days and are at risk for severe disease.

The latest analysis was presented during IDWeek, the annual meeting of infectious disease organisations, including the Infectious Diseases Society of America.

Shares of Merck were up 2.3 per cent at US$75.04 on Wednesday afternoon on the New York Stock Exchange.

[Kb27]

Malaysia in talks to procure Merck's COVID-19 pills

KUALA LUMPUR, Oct 2 (Reuters) - Malaysia is in talks to procure an experimental antiviral pill developed by Merck & Co (MRK.N) for COVID-19 treatment, the health minister said on Saturday.

Health Minister Khairy Jamaluddin said in a tweet that he has started negotiations to procure the new drugs, referring to a Reuters story on Friday that the pill developed by Merck could halve the chances of dying or being hospitalised for those most at risk of contracting severe COVID-19.

"As we transition to living with COVID, we will be adding new, innovative treatment options to our arsenal in addition to vaccines," he said.

Merck and partner Ridgeback Biotherapeutics are planning to seek U.S. emergency use authorisation for the pill as soon as possible and to make regulatory applications globally.

The pill molnupiravir, designed to introduce errors into the genetic code of the virus, would be the first oral antiviral medication for COVID-19.

Current treatment options include Gilead Sciences Inc's (GILD.O) infused antiviral remdesivir and generic steroid dexamethasone, both of which are generally only given once a patient has already been hospitalised.

There was not immediate response to a request to clarify if the ministry's negotiations also included Gilead Sciences or Pfizer which is developing an antiviral pill with Swiss drugmaker Roche Holding AG (ROG.S).

[Blueray]

Coronavirus: Hong Kong looking to procure world’s first Covid-19 pill

Quote

Sources tell the Post that Hospital Authority is planning to buy hundreds of courses of the antiviral medication, known as molnupiravir

https://www.scmp.com/news/hong-kong/health-environment/article/3150999/coronavirus-hong-kong-looking-procure-worlds

[Kb27]

First pill to treat Covid gets approval in UK

The first pill designed to treat symptomatic Covid has been approved by the UK medicines regulator.

The tablet - molnupiravir - will be given twice a day to vulnerable patients recently diagnosed with the disease.

In clinical trials the pill, originally developed to treat flu, cut the risk of hospitalisation or death by about half.

Health secretary Sajid Javid said the treatment was a "gamechanger" for the most frail and immunosuppressed.

In a statement he said: "Today is a historic day for our country, as the UK is now the first country in the world to approve an antiviral that can be taken at home for Covid."

 

First oral treatment

Molnupiravir, developed by the US drug companies Merck, Sharp and Dohme (MSD) and Ridgeback Biotherapeutics, is the first oral antiviral medication for Covid which can be taken as a pill rather than injected or given intravenously.

It targets an enzyme that the virus uses to make copies of itself, introducing errors into its genetic code. That should prevent it from multiplying, so keeping virus levels low in the body and reducing the severity of the disease.

Merck said that approach should make the treatment equally effective against new variants of the virus as it evolves in the future.

The UK regulator, the MHRA, said the tablet had been authorised for use in people who have mild to moderate Covid and at least one risk factor for developing severe illness such as obesity, old age, diabetes or heart disease.

The organisation's chief executive, June Raine, described the treatment as "another therapeutic to add to our armoury against Covid-19".

"It is the world's first approved antiviral for this disease that can be taken by mouth rather than administered intravenously," she said.

"This is important, because it means it can be administered outside of a hospital setting, before Covid-19 has progressed to a severe stage."

The UK has initially ordered 480,000 courses of molnupiravir to be delivered by the end of the year, along with 250,000 courses of a similar experimental drug currently being developed by the US drug company Pfizer.

England's deputy chief medical officer, Prof Jonathan Van-Tam, warned on Wednesday of some "hard months to come" in the pandemic.

He said that while Covid cases appeared to have stabilised, deaths were rising and there were signs infections were starting to "penetrate" older age groups.

The UK recorded 41,229 Covid cases on Wednesday and 217 deaths within 28 days of a positive test.

[Playtime]

Get ready for the mother of all fake medicine tsunami... this has all the makings of the fake little orange pill beating the fake little blue pill.

 Soon this will turn up at geylang back lane... 

[inlinesix]

 

[mersaylee]

That's such a depressing colour...can't they cum out with happy pill colour like yellow or orling? 😁

[Kb27]

apparently the drug has its detractors.

The Dangers Of Molnupiravir

Yesterday I wrote about the potential dangers the antiviral drug molnupiravir could unleash by supercharging new SARS-CoV-2 variants. Today, my focus is on the people who may receive the drug as a treatment and the possibility that molnupiravir could lead to cancerous tumors in those patients and birth defects in the unborn.

Molnupiravir is a relatively new drug, initially developed as an antiviral treatment for influenza. Molnupiravir’s metabolite, an active compound called NHC, has been known and studied for decades. The metabolite works by creating havoc with RNA polymerase, the enzyme critical for viral replication. As I described in yesterday’s article, the drug inserts errors into the virus’ genetic code every time it copies itself. Insert enough errors and you essentially kill off the virus, preventing it from replicating any further. 

Against other coronaviruses, like MERS-CoV and mouse hepatitis virus (MHV), the drug was found to create up to more than a hundred mutations at every section of the viral genome. Against SARS-CoV-2, molnupiravir’s manufacturers Merck and Ridgeback say that the drug’s antiviral effects are powerfully effective, limiting the virus’ ability to proliferate unchecked and cutting the risk of hospitalization and death by half among those infected. The trouble with the drug, however, is that its mutagenic powers may also create havoc among other enzymes in the body, including the nucleic acids in our own healthy DNA. 

As far back as 1980, researchers have been trying to understand just how damaging NHC, molnupiravir’s metabolite, can be to our own healthy cells. Earlier this year, a study published in the Journal of Infectious Diseases found that the metabolite could indeed be incorporated into and mutate within our host DNA. As others have pointed out, just because something is mutagenic doesn’t mean it’s entirely bad — even sunlight is mutagenic. But, just like sunlight, overexposure can lead to long term ill effects, like cancer. In the case of molnupiravir, the drug may not just lead to the growth of cancerous tumours but also, potentially, to birth defects, either through sperm precursor cells or in pregnant women.

Molnupiravir has been tested for mutagenicity in animals before being moved to human trials, where it is being tested for safety. But that doesn’t mean the drug is fully in the clear. The pool of participants in the clinical trial — around 1,500 patients — is too small to pick up on rare mutagenic events and the early nature of the trial is too short-term to provide a proper view of issues that may occur months, if not years, down the road. Merck would do well to remember their experience with Vioxx, a painkiller that was deemed safe based on initial studies, but later proved deadly. The FDA originally approved Vioxx based on a safety database that included around 5000 people. Five years later, the drug was recalled after a broader and longer term study found a definitive link between the drug and rare cardiac events. There is evidence that during the time the drug was on the market it may have killed up to 56,000 people and left up to 140,000 with heart disease. 

I believe Merck and Ridgeback know there are questions around the possible mutagenicity and teratogenicity of molnupiravir that need to be answered. Both male and female participants in the trial were asked to abstain from sex or use contraception during and shortly after the trial. And reporters have asked the manufacturers about potential mutagenic effects, which Merck has answered by saying that, “the drug will be safe if used as intended and at the concentrations where we have looked and in the concentrations which we are achieving in patients.” 

 

This isn’t the first time a mutagenic drug has been tested for antiviral activity. In that respect, our prior experience with another antiviral drug, favipiravir, may be of interest. It too is an antiviral that targets RNA polymerase, initially developed as a treatment for influenza and, like molnupiravir, now being tested against SARS-CoV-2. The two drugs work in a similar fashion, interchanging two of the four letters of the viral RNA code to create copying errors — molnupiravir switches uracil (U) and cytosine (C), while favipiravir switches guanosine (G) and adenosine (A). Like molnupiravir, favipiravir works by creating enough copying errors during replication to essentially kill off the virus.

The study on mutagenicity of the molnupiravir metabolite in the Journal of Infectious Diseases earlier this year also tested favipirivir. The study found that the molnupiravir metabolite, NHC, was a far more potent mutagen than favipirivir (FAV) (see Figure 1), which is a drug that has widely known issues related to teratogenicity and links to birth defects.

Because of this, favipiravir has not been approved in the US or the UK, and is only approved in Japan under the strictest of regulations and for the most severe form of influenza, for which no other drugs exist. The challenge with approval of any drug, even under the strictest of regulations, is that once approved it can be used for many purposes, off-label. Favipiravir is already reportedly being distributed and used in Hungary as a treatment for Covid-19, despite no clear evidence of its value and its known risks. This is a danger not just to those receiving the drug, but also — as I wrote about in my previous article on molnupiravir — a danger to all of us, given the potential of drugs like these to supercharge the creation of viral variants.

In November, the FDA will debate the use of molnupiravir only as a treatment for high-risk individuals with mild to moderate disease. But an initial emergency use approval for the drug may lead to unknown harm to all those who receive it. Yesterday, I wrote that if the FDA approves the drug it should be only on a very narrow basis and include a black box warning to emphasize the potential danger of using the drug at suboptimal doses or for large numbers of people for preventive purposes. To that, I add the need for specific warnings for men and women who are actively trying to become pregnant and for women who are already pregnant — under no circumstance should these individuals receive this treatment. I hope that Merck, Ridgeback, the FDA and the CDC explore the dangers of molnupiravir thoroughly before granting emergency use approval of the drug, especially as other potentially safer antivirals are already on the way. This drug could harm the very people it’s meant to help, those receiving the drug and all of us around them, should new more powerful variants be unleashed.

[Kb27]

FDA approve Merck molnupiravir, but it seems to come a bit late with efficacy of 30%, compared to Pfizer 90%.

 

U.S. authorizes Merck pill as second at-home COVID-19 treatment

Dec 23 (Reuters) - The U.S. on Thursday authorized Merck & Co's (MRK.N) antiviral pill for COVID-19 for certain high-risk adult patients, a day after giving a broader go-ahead to a similar but more effective treatment from Pfizer Inc (PFE.N).

The U.S. Food and Drug Administration said Merck's drug could be used when other authorized treatments are not accessible or clinically appropriate.

The drug, molnupiravir, was developed with Ridgeback Biotherapeutics and shown to reduce hospitalizations and deaths by around 30% in a clinical trial of high-risk individuals early in the course of the illness.

The authorization allows use of the drug for mild-to-moderate COVID-19 and along with the Pfizer pill, could be an important tool against the fast-spreading Omicron variant, which is now dominant in the United States.

Pfizer's drug, Paxlovid, was authorized on Wednesday for people aged 12 and older and has shown to be nearly 90% effective in preventing hospitalizations and deaths in patients at high risk of severe illness, according to trial data.

The FDA says some patients should avoid Pfizer's two-drug regimen because it includes an older antiviral called ritonavir that is known to have interactions with some other prescription medicines. It is also not recommended for people with severe kidney issues.

Merck plans to ship hundreds of thousands of treatment courses in coming days and 1 million over the next few weeks. Pfizer plans to ship about 250,000 courses in the next month.

Availability of other treatments is the first consideration for doctors thinking of prescribing Merck's treatment, according to Patrizia Cavazzoni, the director of FDA's Center for Drug Evaluation and Research.

The FDA has authorized intravenous treatments, mostly for hospital use, called monoclonal antibodies but availability is limited and efficacy against the Omicron variant is lower.

FDA official John Farley said during a press briefing that GlaxoSmithKline's (GSK.L) and Vir Biotech's (VIR.O) antibody drug - which has been shown to work against Omicron - is expected to be in short supply this winter.

Merck said that its treatment had advantages over the Pfizer pill.

"It doesn't require any second drug to boost its efficacy, and you can give it in a variety of special patient populations, including people who have significant issues with liver function or kidney function," Nick Kartsonis, Merck's senior vice president of clinical research for vaccines and infectious diseases, told Reuters.

"This approval comes at the right time since more COVID-19 treatments are needed to supplement the vaccination effort, especially in light of variants of concern," said Cantor Fitzgerald analyst Louise Chen.

Nearly 62% of people in the United States are fully vaccinated, leaving many Americans unprotected against a wave of Omicron infections. Two doses of the highly successful vaccine from Pfizer Inc and BioNTech SE are only somewhat protective against infection with the Omicron variant while a third dose improves the immune response.

Merck's and Pfizer's antiviral both work by preventing the virus from replicating. Merck's pill does so by introducing errors into the genetic code of the virus.

Some of the FDA's experts have said that could lead to more troublesome variants.

There have also been some safety concerns around the drug because it may affect bone cartilage and growth.

Due to that reason, Merck's drug is not authorized for use in patients younger than 18, the FDA said. The pill is not recommended for use during pregnancy, the agency added.

The agency advised that men of reproductive potential use a reliable method of birth control during treatment with molnupiravir, and for at least three months after the final dose.

The drug is meant to be taken twice a day - four pills each time - for five days, making a full treatment course 40 pills. The treatment was priced at about $700 per course in a deal with the U.S. government for up to 5 million courses.

The U.S. government has ordered 10 million courses of the Pfizer drug at a price of $530 per course compares to the deal with Merck for as many as 5 million courses of molnupiravir at a price of $700 per course.

Merck has said molnupiravir, which helps prevent the virus from replicating, should be effective against any variant, including the new Omicron variant.