TIT LAST the news in the fight against covid-19 is encouraging. Two new antiviral drugs were found to be so effective that clinical trials ended prematurely. Data from these trials have not yet been published. However, regulators are rushing to consider the general use of the drugs. They will fill a big gap in the toolbox doctors are using to fight the virus and may well help end the global pandemic.
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The new drugs are molnupiravir (Lagevrio), developed by Merck, a pharmaceutical company, in collaboration with Ridgeback Biotherapeutics, a biotechnology company, and Paxlovid, which was developed by Pfizer. All three are American companies. People most at risk of severe covid effects are much less likely to be hospitalized or die if they take any of these pills within five days of onset of symptoms.
Merck said in October that molnupiravir roughly halves the risk of hospitalization or death when given to patients with a risk factor for covid, such as obesity or heart disease. Regulators in America, Europe and the World Health Organization are evaluating the drug. Britain has approved it and will start using the treatment next month. On November 5, Pfizer said its pill reduced the risk of hospitalization or death by 89% if taken within three days. (In fact, during his trial, no patient died while taking Paxlovid within five days of experiencing symptoms.)
Molnupiravir is called a prodrug, which means it gets converted to its active form when it gets inside cells. Once there, it is incorporated into the genetic material of the virus, disrupting its ability to replicate. Errors accumulate in the genetic material of the virus, a process known as the “error catastrophe”. Animal testing has raised concerns that the drug may pose risks to unborn children, which is why the UK government has advised against its use during pregnancy or breastfeeding. Other regulators may issue similar warnings.
Paxlovid is actually a combination of two drugs: an existing one called ritonavir, which is given with a new protease inhibitor known asPF-07321332. The protease inhibitor was designed to bind to and block the protease enzymes that sars-cov-2 uses to replicate. Ritonavir prevents too rapid breakdown of the protease inhibitor in the body.
Molnupiravir and Paxlovid are also known as ‘small molecule’ drugs. They are easy to manufacture molecules. Both companies say the price of the drugs will vary depending on the wealth of the country buying them. This will likely mean that rich countries will pay $ 700 for a five-day course of pills, while poorer ones will pay around $ 20, and perhaps less as the cost of manufacturing drops.
Although both companies have said they intend to make these drugs widely available around the world, Merck already has an advantage. He has signed a number of licenses that allow other manufacturers to produce the drug and has set aside 3 million doses for low- and middle-income countries. This is to ensure that rich countries do not monopolize the supply of new drugs as they have done with vaccines. Merck plans to make 10 million doses this year and 20 million next year. Generic manufacturers will do a lot more. Pfizer, which has yet to receive regulatory approval, expects 180,000 boxes of tablets to be produced by the end of this year, and 21 million in the first half of 2022.
These drugs herald a second major turning point in the pandemic (the first being vaccines). The increase in the number of cases across Europe suggests that there will be a high demand for such drugs to avoid hospitalization. While patients wait for their arrival, doctors may also consider the use of fluvoxamine, an antidepressant drug that also appears to reduce the risk of covid.
As new treatments roll out, some scientists and doctors will be concerned about resistance to the virus developing, especially if patients do not complete their treatment. Staying one step ahead of sras-cov-2 will require planning for such an eventuality. This means deducing which antiviral drugs can be given in combination to create a therapy that the virus will be hard pressed to overcome. ■
This article appeared in the Science & Technology section of the print edition under the title “Pills with promise”