How Merck’s Covid-19 pill, molnupiravir, could change the Covid-19 pandemic

Pharmaceutical giant Merck on Friday announced good news for people with Covid-19: its antiviral drug, molnupiravir, reduced the risk of hospitalization and death in at-risk patients by 50%, according to interim analysis of the society.

A new and effective Covid-19 treatment – if approved by health regulators – could be a versatile tool for doctors to treat Covid-19 patients and could ultimately save lives. While there are a number of treatments for Covid-19 on the market, many are expensive, difficult to administer, not readily available, or ineffective. Meanwhile, treatments that have little evidence behind them, like the antiparasitic drug ivermectin and the antimalarial drug hydroxychloroquine, have gained traction in some circles.

Molnupiravir, originally developed to treat influenza, could solve many of these challenges. It is given as a pill twice a day for five days, compared to other Covid-19 treatments that require expensive intravenous transfusions, such as monoclonal antibodies and convalescent plasma. Remdesivir, an antiviral drug, currently the only drug fully approved by the Food and Drug Administration to treat Covid-19, must also be given into the bloodstream.

A drug like molnupiravir (the name refers to Thor’s hammer, Mjölnir) could also help address persistent gaps in Covid-19 vaccine coverage, both in the United States and abroad.

However, the results were announced in a press release from the company, which carries less scientific weight than a peer-reviewed article or even a pre-printed article that presents data for review by outside scientists. Merck’s findings come from a phase 3 randomized clinical trial involving 775 adult patients with Covid-19. Participants had mild to moderate illness and were considered at risk but not hospitalized when the trial began in early August.

By day 29 of the trial, 7.3% of patients who received molnupiravir had died or were hospitalized, compared to 14.1% of patients in the placebo group (meaning they did not receive the drug) . Merck claims that molnupiravir was also effective against variants of the coronavirus, including gamma, delta, and mu. The trial was halted, with regulatory approval, once these results showed the drug’s effectiveness.

“With these compelling results, we are optimistic that molnupiravir may become an important drug in the global pandemic effort and will add to Merck’s unique legacy of advancing breakthroughs in disease. infectious when they are needed most, ”Robert Davis, CEO and President of Merck, said in a statement.

Merck and collaborator Ridgeback Biotherapeutics said they would seek emergency use authorization for the drug from the U.S. Food and Drug Administration, which would allow doctors to start prescribing it to patients. The federal government is already planning its potential approval: it has committed to purchasing 1.7 million molnupiravir treatments for $ 1.2 billion (about $ 700 per course), and production of the drug has already started. Ridgeback Biotherapeutics and Merck plan to do 10 million courses of the drug by the end of the year.

But it will still be weeks or months before most people have access to the little brown pill. And even when it is available, there may still be refractories resistant to treatment for the disease.

How Merck’s new antiviral drug, molnupiravir works

Viruses are difficult beasts to catch. They are passive parasites and cannot reproduce without hijacking the machinery of a host cell. It is therefore very difficult to find a drug that can interfere with the life cycle of a virus without also causing collateral damage to healthy human cells. And because viruses mutate so quickly, effective treatment may become less so over time.

Compare that to bacteria, which contain all the biological material they need to make copies of themselves. Their machinery is different enough from human cells that a class of drugs called antibiotics can kill many bacteria with minimal harm to humans.

Molnupiravir works a lot like remdesivir, an antiviral drug (-vir is a commonly used suffix for antiviral drugs). The SARS-CoV-2 virus, which causes Covid-19, copies itself by encoding instructions on RNA, which is made up of “basic” molecules identified by the letters A, C, U, and G. While the remdesivir mimics A (adenosine), molnupiravir can mimic U (uracil) or C (cytosine).

When the virus incorporates remdesivir into its RNA, the drug blocks its reproductive cycle. Molnupiravir works a little differently, causing genetic mutations that hamper the virus.

Mostly, these drugs can trick the virus, but they don’t trick human cells, so they have a targeted effect and for the most part leave human cells alone.

Merck did not note any specific side effects of molnupiravir in its press release and said the complication rate was similar between the placebo group and the treatment group in the clinical trial. Unspecified side effects occurred in 35 percent of molnupiravir recipients, but occurred in 40 percent of the placebo group.

Molnupiravir was the subject of some controversy in the early stages of its development. Some researchers have previously raised concerns that the mechanism of molnupiravir could lead to unforeseen problems. Rick Bright, the former head of the Biomedical Advanced Research and Development Authority, alleged in a whistleblower complaint last year that his agency was pressured to fund the manufacture of the drug (then known as EIDD- 2801) before receiving adequate security data. The FDA tends to pay special attention to safety concerns when evaluating which drugs to use in an emergency.

Molnupiravir fills critical gap in Covid-19 response

While the United States has several very effective vaccines that help our immune system fight Covid-19, the vaccination rate has slowed and many refractories remain. At the same time, many other countries still do not have access to enough vaccines. The unvaccinated continue to account for the majority of hospitalizations and deaths, with currently around 2,000 deaths per day in the United States alone.

Treatments for Covid-19 therefore remain an essential element of the response to the pandemic. But developing new drugs to treat one disease is expensive and time consuming, which is why researchers have been eager to find standard therapies that have already been found safe to use against other diseases. Some have been shown to be successful, such as the corticosteroid dexamethasone. Scientists have also seen promise in the antidepressant drug fluvoxamine as a therapy.

New drugs like molnupiravir require more testing and review, but they offer the possibility of a stronger, more focused approach. A drug like molnupiravir might be particularly helpful because it is given in the early stages of the disease. Since it is only a pill, it can save the patient from going to a clinic for a transfusion of treatments such as monoclonal antibodies. This reduces the chances of an infected patient transmitting the virus to medical personnel and avoids the potential complications associated with transfusions.

And while $ 700 for a course of molnupiravir isn’t exactly cheap, a transfusion alone can cost $ 1,000, and that’s on top of the cost of intravenous drugs. A course of monoclonal antibodies can cost $ 2,100, while remdesivir can cost $ 3,100.

Pills are also much easier to store and transport than transfused drugs, so they can reach more remote areas with fewer resources.

This is why some of the most important effects of molnupiravir could be happening in other countries, especially in places where Covid-19 vaccines have not yet taken up much space. Merck said it is implementing tiered pricing for molnupiravir, which means it could cost less in other countries, and is licensing five generic drug manufacturers in India to increase supplies. .

Treatments help people get better, but it’s important to remember that vaccination is still the most effective tactic in controlling the pandemic. Vaccination can prevent disease in the first place, and even the most expensive vaccines are very inexpensive compared to most disease therapies. The first two doses of the Pfizer / BioNTech vaccine and the Moderna vaccine cost around $ 50.

Other measures beyond drugs also remain essential. Wearing masks, social distancing and Covid-19 testing are always effective, and the arrival of an effective drug will not be a reason to let our guard down. The existing pillars of the pandemic response will remain crucial in bringing this deadly disease under control.