What Are the Treatments for Covid and How Good Are They?

(Bloomberg) --

In the battle against Covid-19, researchers have been able to move faster and go further with vaccines that prevent the disease than therapies to treat the sick. The search for reliable drugs has followed a checkered path with some therapies losing favor after being authorized for emergency use. Nearly two years after the first cases of Covid were reported in China, two pills have emerged that even skeptical scientists are hailing as a potential turning point in the pandemic. The medicines are intended for patients who are early on in their illness, not yet in the hospital, but at risk of developing severe disease. More research is needed to provide better therapy for severely ill patients. 

1. What are the different types of treatments?

• Antivirals: The promising new pills fall into this relatively new class of medicine. One, Merck & Co.’s molnupiravir, cut the risk of hospitalization among high-risk patients by about 50%, according to an interim analysis of trial data. On Nov. 4, the U.K. medicines authority became the first to approve the drug. Pfizer Inc.’s pill, called Paxlovid, reduced hospitalization and death among high-risk patients by 89%. Merck’s drug works by inducing errors in viral genes; Pfizer’s blocks an enzyme that allows the coronavirus to grow. As pills, they’re easier to administer than Gilead Sciences Inc.’s remdesivir, an antiviral delivered by infusion that was the first Covid medication backed by early clinical data. The U.S. Food and Drug Administration cleared it for emergency use in May 2020 after research showed it helped hospitalized patients recover from Covid more quickly than standard care alone; the agency gave it full regulatory approval that October, making it the first to obtain formal clearance for treating Covid. The next month, the World Health Organization recommended against using remdesivir to treat hospitalized patients, based on studies showing a lack of impact on patient improvement and survival. Some infectious disease specialists say antivirals are most likely to be effective when used early, before the infection overwhelms the body. Other antiviral drugs that have been tried include favipiravir, a treatment for the flu virus made by Japan’s Fujifilm Holdings Corp. Japanese regulators haven’t cleared the drug for Covid treatment, but it’s been authorized in India and Russia.
• Antibody therapies: These are protective antibodies produced in a lab that mimic the body’s immune defenses against the coronavirus. U.S. regulators authorized two antibody therapies in late 2020 -- REGEN-COV from Regeneron Pharmaceuticals Inc. and bamlanivimab from Eli Lilly & Co. -- and a third in May called sotrovimab from GlaxoSmithKline Plc and Vir Biotechnology Inc. All three were cleared for use in patients with mild-to-moderate Covid with a goal of preventing hospitalization or death. In April, the FDA revoked the authorization for solo use of bamlanivimab due to fears of reduced effectiveness against coronavirus variants, and later halted shipments of Lilly’s combination of bamlanivimab and another antibody, etesevimab. Since then, use of the antibody cocktail has resumed. In July, the FDA authorized the use of Regeneron’s REGEN-COV preventively in high-risk patients who’ve been exposed to Covid or live in high-risk settings like nursing homes; results released in November suggested it cut the risk of contracting Covid by 82% for as long as eight months. In June, final results from a trial of Glaxo and Vir’s sotrovimab suggested it reduced deaths and hospitalizations by 79%. None of these treatments is cleared for treating severely ill patients, although the WHO in September recommended using REGEN-COV for those who have not developed antibodies despite active infection.
• Convalescent plasma infusions: This is a basic version of antibody therapy that involves collecting plasma, the liquid part of blood, from people who’ve recovered from Covid-19 and developed antibodies to the coronavirus, and transfusing it into those who are still sick. U.S. regulators in late August 2020 granted emergency authorization for these infusions, limited to hospitalized patients. However, experts convened by the U.S. National Institutes of Health broke with the FDA the next month, saying there wasn’t enough evidence to recommend for or against the treatment. Critics of the FDA authorization pointed to the agency’s earlier reversal on the malaria drugs chloroquine and hydroxychloroquine. The agency in March 2020 authorized both for use against Covid after then-President Donald Trump repeatedly touted them. The decision was criticized by other scientists as premature, and in mid-June, the agency reversed itself after determining the drugs were unlikely to work against the coronavirus and could have dangerous side effects.
• Steroids: In June 2020, a University of Oxford study showed the cheap steroid dexamethasone improved survival in patients with Covid who needed breathing assistance, making it the first treatment to show life-saving promise. A generic made by companies including Mylan NV and Merck & Co., dexamethasone fights excessive inflammation, sometimes called a cytokine storm, which can be worse than the viral infection itself.
• Blood thinners: Because Covid can cause blood clots that destroy people’s organs, some doctors are finding it helpful to treat patients with blood thinners.

2. What else is 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. Interferon deficiencies may underlie about 14% of severe Covid cases, scientists reported. However, interferon therapy didn’t help hospitalized patients in a study reported in October. 

3. 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.

4. 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.

The Reference Shelf

• Related QuickTakes on Delta and booster vaccines, coronavirus variants, and vaccine inequality.
• A living WHO guideline on drugs for Covid-19, and a tracker from the Milken Institute.
• The U.S. National Institutes of Health compares the drug approval process in the U.S. to that in China.
• A commentary published by George Mason University’s Mercatus Center examines China’s reforms of its drug approval process.

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