WHO launches global megatrial of the four most promising coronavirus treatments (Science)
Excerpt:
Trump is a "big fan" of chloroquine but, as Fauci explained:
"We're trying to strike a balance between making something with a potential of an effect to the American people available, at the same time that we do it under the auspices of a protocol that would give us information to determine if it's truly safe and truly effective. But the information that you're referring to specifically is anecdotal, it was not done in a controlled clinical trial. So you really can't make any definitive statement about it."
Trump trumpeted that chloroquine had shown “very, very encouraging early results” and said “we’re going to be able to make that drug available almost immediately.” FDA Commissioner Stephen Hahn, an oncologist, clarified that the drug would be available “in the setting of a clinical trial — a large, pragmatic clinical trial — to actually gather that information and answer the question that needs to be answered and — asked and answered.”
Excerpt:
Scientists have suggested dozens of existing compounds for testing but WHO is focusing on what it says are the four most promising therapies: an experimental antiviral compound called remdesivir; the malaria medications chloroquine and hydroxychloroquine; a combination of two HIV drugs, lopinavir and ritonavir; and that same combination plus interferon-beta, an immune system messenger that can help cripple viruses. Some data on their use in COVID-19 patients has already emerged—the HIV combo failed in a small study in China-but WHO believes a large trial with a greater variety of patients is warranted.
Chloroquine and hydroxychloroquine
At a press conference on Friday, President Donald Trump called chloroquine and hydroxychloroquine a “game changer.” “I feel good about it,” Trump said. His remarks have led to a rush in demand for the decades-old antimalarials. (“It reminds me a little bit of the toilet paper phenomenon and everybody's running to the store,” says Caplan.)
The WHO scientific panel designing SOLIDARITY had originally decided to leave the duo out of the trial but had a change of heart at a meeting in Geneva on 13 March, because the drugs “received significant attention” in many countries, according to the report of a WHO working group that looked into the drugs’ potential. The widespread interested prompted “the need to examine emerging evidence to inform a decision on its potential role.”
The available data are thin. The drugs work by decreasing the acidity in endosomes, compartments inside cells that they use to ingest outside material and that some viruses can coopt to enter a cell. But the main entryway for SARS-Cov-2 is a different one, using its so-called spike protein to attach to a receptor on the surface of human cells. Studies in cell culture have suggested chloroquines have some activity against SARS-CoV-2, but the doses needed are usually high—and could cause serious toxicities.
Encouraging cell study results with chloroquines against two other viral diseases, dengue and chikungunya, didn’t pan out in people in randomized clinical trials. And non-human primates infected with chikungunya did worse when given chloroquine. “Researchers have tried this drug on virus after virus, and it never works out in humans. The dose needed is just too high,” says Susanne Herold, an expert on pulmonary infections at the University of Giessen, Germany.
Results from COVID-19 patients are murky. Chinese researchers who report treating more than 100 patients with chloroquine touted its benefits in a letter in BioScience, but the data underlying the claim have not been published. All in all, more than 20 COVID-19 studies in China used chloroquine or hydroxychloroquine, WHO notes, but their results have been hard to come by. “WHO is engaging with Chinese colleagues at the mission in Geneva and have received assurances of improved collaboration; however, no data has been shared regarding the chloroquine studies.”
Researchers in France have published a study in which they treated 20 COVID-19 patients with hydroxychloroquine. They concluded that the drug significantly reduced viral load in nasal swabs. But it was not a randomized controlled trial and it didn’t report clinical outcomes such as deaths. In guidance published on Friday, the US Society of Critical Care Medicine said that “there is insufficient evidence to issue a recommendation on the use of chloroquine or hydroxychloroquine in critically ill adults with COVID-19.”
Hydroxychloroquine in particular might do more harm than good. The drug has a variety of side effects and can in rare cases harm the heart. Since people with heart conditions are at higher risk of severe COVID-19, that is a concern, says David Smith, an infectious disease physician at the University of California, San Diego. “This is a warning signal, but we still need to do the trial,” he says. What’s more, a rush to use the drug for COVID-19 might make it harder for the people who need it to treat their rheumatoid arthritis or malaria.
Trump is a "big fan" of chloroquine but, as Fauci explained:
"We're trying to strike a balance between making something with a potential of an effect to the American people available, at the same time that we do it under the auspices of a protocol that would give us information to determine if it's truly safe and truly effective. But the information that you're referring to specifically is anecdotal, it was not done in a controlled clinical trial. So you really can't make any definitive statement about it."
Trump trumpeted that chloroquine had shown “very, very encouraging early results” and said “we’re going to be able to make that drug available almost immediately.” FDA Commissioner Stephen Hahn, an oncologist, clarified that the drug would be available “in the setting of a clinical trial — a large, pragmatic clinical trial — to actually gather that information and answer the question that needs to be answered and — asked and answered.”
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