One of the world’s biggest trials of COVID-19 therapies released its long-awaited interim results yesterday—and they’re a letdown. None of the four treatments in the Solidarity trial, which enrolled more than 11,000 patients in 400 hospitals around the globe, increased survival—not even the much-touted antiviral drug remdesivir. Scientists at the World Health Organization (WHO) released the data as a preprint on medRxiv last night, ahead of its planned publication in The New England Journal of Medicine.
Yet scientists praised the unprecedented study itself and the fact that it helped bring clarity about four existing, ”repurposed” treatments that each held some promise against COVID-19. “It’s disappointing that none of the four have come out and shown a difference in mortality, but it does show why you need big trials,” says Jeremy Farrar, director of the Wellcome Trust. “We would love to have a drug that works, but it’s better to know if a drug works or not than not to know and continue to use it,” says WHO’s chief scientist, Soumya Swaminathan.
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The prospects of two of the four treatments—the malaria drug hydroxychloroquine and the HIV drug combination ritonavir/lopinavir—had faded after another large study, the United Kingdom’s Recovery trial, showed they did not increase survival in June. After analyzing that study and its own data up until then, WHO decided to drop both from the study.
There was still hope for remdesivir and for interferon-beta, which had initially been given in combination with ritonavir/lopinavir but was tested as a standalone drug after the Recovery data came out. But neither of those treatments lowered mortality or delayed the moment patients needed ventilation to help them breathe. The results in these two treatment arms are likely to be the most scrutinized.
Remdesivir, which attacks a specific enzyme in several RNA viruses and was previously tested against Ebola, was initially seen as a promising candidate. In a U.S. trial with more than 1000 COVID-19 patients published last week,
those who received remdesivir had a shorter recovery time than patients in the control group, but there was no significant difference in mortality. Two smaller trials found few significant benefits. Remdesivir received an emergency use authorization from the U.S. Food and Drug Administration (FDA) in May for severe COVID-19 patients that was later expanded to include all patients.
But the Solidarity trial suggests the drug does little in severe cases.
Of 2743 hospitalized patients who received the drug, 11% died, versus 11.2% in a control group of roughly the same size. The difference is so small it could have arisen by chance.
When the authors pooled Solidarity’s data with those from the three other trials, they found a slight reduction in mortality that wasn’t statistically significant either. “This absolutely excludes the suggestion that remdesivir can prevent a substantial fraction of all deaths,” the authors write. “The confidence interval is comfortably compatible with prevention of a small fraction of all deaths but is also comfortably compatible with prevention of no deaths.”
“This trial doesn’t help remdesivir, that’s for sure,” says Eric Topol, director of the Scripps Research Translational Institute. “It’s not a dead duck as much as hydroxychloroquine, but it certainly is not the hope that was initially signaled.”
But the drug’s manufacturer, Gilead Sciences, casts doubt on the study. “The trial design prioritized broad access, resulting in significant heterogeneity in trial adoption, implementation, controls and patient populations,” the company says in a statement, “and consequently, it is unclear if any conclusive findings can be drawn from the study results.”
Gilead received the manuscript about Solidarity on 28 September, according to WHO. On 8 October, before the results became public, the company signed a $1 billion deal with the European Commission for a 6-month supply of the drug.