Where Are We in the Quest for Covid Treatments?: QuickTake

Sept. 24, 2021, 1:39 AM

In the battle against the Covid-19 pandemic, vaccines have emerged as the weapon of choice. Prevention of disease is always preferable to treatment, and in this case, vaccines have proven far more targeted and effective than the few Covid therapies that have emerged so far. Several, including some that received emergency-use authorization from regulators, have lost favor or been discarded as the struggle goes on to understand the coronavirus that causes Covid and how it impacts cells, tissues and ultimately the human body. While the list of disappointments is long, some treatments have been shown to work, although more research is needed to provide effective therapy for severely ill patients.

1. What are the different types of treatments?

  • Antibody therapies: These involve producing antibodies in a lab that can be safely administered to patients to mimic the body’s immune defenses to 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 against mild-to-moderate Covid with a goal of preventing cases from worsening to the point where patients are hospitalized or die. In April, however, the Food and Drug Administration revoked the authorization for solo use of bamlanivimab due to fears of reduced effectiveness against coronavirus variants, and the U.S. government canceled a deal for thousands of doses. In June, the government halted shipments of Lilly’s combination of bamlanivimab and another antibody, etesevimab, because of similar concerns about effectiveness. Results for REGEN-COV and sotrovimab, so far, have been more promising. REGEN-COV reduced death and hospitalization in high-risk patients by roughly 70%, according to data from a major studyreleased in April ahead of review by experts uninvolved in the research. In July, the FDA authorized its use preventively in high-risk patients who’ve been exposed to Covid or live in high-risk settings like nursing homes. In June, final results of the clinical trial for Glaxo’s sotrovimab suggested it reduced deaths and hospitalizations by 79%. None of these treatments is cleared for treating severely ill patients, although the World Health Organization 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.
  • Antivirals: This would be the drug type of choice, but it’s a relatively new class of medicine compared with antibiotics, and design can be challenging. Gilead Sciences Inc.’s antiviral remdesivir was the first medication backed by early clinical data. The FDA approved the drug Oct. 22, 2020, making it the first to obtain formal clearance for treating Covid. Earlier, the agency had cleared it for emergency use after researchshowed it helped hospitalized patients recover from Covid more quickly than standard care alone. However, the next month the WHO 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 such 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., known for its photo film and cameras but also operating as a health-care company. Japanese regulators haven’t cleared the drug for Covid treatment, but it’s been authorized in India.
  • 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 publishedin September 2020 focused on the role of an immune substance called interferon that helps orchestrate the body’s defenses. The studies 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.

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 long Covid, the delta variant and the challenges of reaching herd immunity.
  • 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.

(Updates with WHO recommendation on REGEN-COV in section 1.)

--With assistance from Robert Langreth, Jason Gale and Olivia Raimonde.

To contact the reporter on this story:
John Lauerman in London at jlauerman@bloomberg.net

To contact the editors responsible for this story:
Eric Pfanner at epfanner1@bloomberg.net

Lisa Beyer, Paul Geitner

© 2021 Bloomberg L.P. All rights reserved. Used with permission.

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