A pill that will help COVID-19 patients avert life-threatening illness has been something of a holy grail for doctors and drugmakers. The earliest therapeutics shown to help have typically been administered to patients via a transfusion or once they have become sick enough to require hospitalization. Two years after the first COVID cases were reported in China, two pill-based treatments have emerged that even skeptical scientists are hailing as potentially huge advances. Intended for newly infected patients at risk of developing severe disease, the medicines promise to reduce hospitalizations and death as well as make users less likely to spread the coronavirus. Research is ongoing to determine how well these and other treatments perform against the Omicron variant of the virus identified in late November.
1. What are the new drugs?
The oral treatment, Paxlovid, developed by Pfizer Inc., is a combination of two antiviral pills. One is designed to block the action of a key enzyme that the coronavirus uses to make copies of itself; the other, the HIV medication ritonavir, helps slow the breakdown of the first, enabling it to remain active in the body for longer and at higher concentrations. The other treatment, molnupiravir, from Merck & Co. And Ridgeback Biotherapeutics LP, was originally developed to treat influenza. The pill inhibits replication of the coronavirus by a mechanism known as lethal mutagenesis. In simple terms, it causes the machinery that reproduces the virus’s genetic material to make mistakes, thereby rendering the copies defective. The U.S. Food and Drug Administration cleared Paxlovid Dec. 22 for emergency use and the next day authorized molnupiravir in cases where other treatments aren’t accessible or appropriate for patients. China granted emergency approval for Paxlovid on Feb. 11 — the first foreign pharmaceutical product specifically targeting COVID it has endorsed.
2. How effective are they?
Paxlovid was shown to reduce the risk of hospitalization or death by 89% in high-risk COVID patients, according to an interim analysis of a trial reported by Pfizer on Nov. 5. The results were the same whether people started treatment within three or five days of developing symptoms. Molnupiravir was found to reduce the likelihood of hospitalization or death by 30% in a study of adults with an increased risk of severe COVID, Merck and Ridgeback reported on Nov. 26.
3. How are they meant to be used?
The FDA said both drugs, available in the U.S. Only by prescription, should be started as soon as possible after a COVID diagnosis and within five days of the start of symptoms. The agency authorized Paxlovid for adults and children 12 and older who weigh at least 88 pounds (40 kilograms). It limited molnupiravir to those 18 and older because of concerns the drug may affect bone and cartilage growth and said the treatment isn’t recommended for use during pregnancy, as it may also have an impact on dividing cells. Paxlovid is administered as three tablets taken together orally twice daily for five days, for a total of 30 tablets. Molnupiravir is given as four capsules taken orally every 12 hours for five days, for a total of 40 capsules.
4. How do these drugs differ from other treatments?
- Affordable and easy-to-administer antivirals are ideal treatments, assuming they are safe and well-tolerated, because they directly counter the virus, limiting the duration of illness and its damage to the body. Japanese drugmaker Shionogi & Co. Said Jan. 31 that an antiviral pill it’s developing was effective in an early clinical study.
- There are other proven therapeutics that specifically target the coronavirus: Gilead Sciences Inc.’s antiviral remdesivir as well as laboratory-made antibodies that mimic the body’s immune defenses against the virus. But these are all administered via infusion, adding complexity and cost that may put them beyond the reach of poor countries. Infusing patients in hospitals can also raise the risk of transmission to medical staff and other patients.
- Other medications reduce hospitalized COVID patients’ symptoms, but don’t directly fight the virus. These include the cheap steroid dexamethasone and interleukin-6 receptor blockers, which can suppress a harmful overreaction of the immune system. Blood thinners can also prevent COVID-linked clots that destroy patients’ organs.
5. How well will treatments work against the Omicron variant?
- The World Health Organization said Dec. 23 that steroids and interleukin-6 receptor blockers are expected to remain effective for managing patients with Omicron infections, since the drugs target inflammation rather than the virus itself.
- Treatments that directly combat the virus are being assessed to see how they perform against Omicron. Pfizer and Merck have said they expect their antiviral pills to stand up to the new variant; lab experiments on both suggest they are active against Omicron. Gilead said it expects its infusion remdesivir to retain efficacy against the variant. The antibody therapies are of greater concern because they target the spike protein that the coronavirus uses to enter cells, and Omicron is characterized by 30 or more changes to that region. U.S. Health authorities restricted use of antibody therapies from Regeneron Pharmaceuticals Inc. And Eli Lilly & Co. After data showed they were “highly unlikely” to be effective against the variant. The authorities said it appeared that GlaxoSmithKline Plc’s antibody treatment, sotrovimab, which it makes in partnership with Vir Biotechnology Inc., would hold up.
6. What other types of treatments are being investigated?
Studies published in September 2020 focused on the role of an immune substance called interferon that helps orchestrate the body’s defenses. The research found that people with low levels of the substance do poorly in fighting off the coronavirus, suggesting that interferon treatments could help in the early stages of the infection and perhaps prevent life-threatening illness. However, interferon therapy didn’t help hospitalized patients in a study reported in October 2021. A number of COVID treatments have lost favor. The WHO in December advised against treating COVID patients with an infusion of plasma from people who’ve recovered from the virus. It said the treatment, while costly, doesn’t improve survival or reduce the need for mechanical ventilation. U.S. Regulators in March 2020 authorized the use of the malaria drugs chloroquine and hydroxychloroquine to treat COVID, and the next June reversed themselves after determining the drugs were unlikely to work against the coronavirus and could have dangerous side effects.
7. How do scientists prove a treatment is effective?
Even if a treatment shows promise in laboratory, animal or early human experiments, rigorous testing is needed to prove it’s both safe and effective. That requires carefully structured and monitored tests known as clinical trials. Typically, these studies are designed to show that patients randomly assigned to get the drug do better than those in a control group who don’t, and that the results aren’t a product of chance. The trials try to subtract all the other influences and factors that might disguise the true effectiveness of the drug. For one thing, patients often recover from viral illness on their own, or improve because of supportive care such as rest and hydration. And some really sick patients might not respond to treatment no matter how effective it is.
8. How long does it take to prove efficacy?
It depends. Drugs that are already approved against one infection and shown to be safe can be tested for effectiveness against another in a matter of months. Experimental drugs may take longer to test, as they have to go through initial studies to evaluate whether they are safe. Other factors that can slow the process include the supply of drug candidates and the availability of patients to test them in. The trials also have to be approved by ethics watchdogs and drug regulators. According to a 2017 review, the median time for regulators to approve a new drug in 2015 was 333 days in the U.S., 422 days in Europe, and 639 days in China. China has since expedited its process. But when drugs are deemed to fill an immediate need, such as in a pandemic, regulators can speed them through the approval process using a number of paths, including emergency authorizations.
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