WHO’s Solidarity Trial Finds No Clinical Benefit for 4 Antivirals in COVID-19

Despite early buzz, remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a failed to reduce mortality, hospital stays.

Since the start of the new coronavirus pandemic last winter, many drug therapies have been touted—and studied—for the treatment of COVID-19, with most (other than older-line steroids such as dexamethasone) proving either ineffective or unsafe (due to adverse events associated with their use).

Now, the researchers behind the World Health Organization’s “Solidarity Trial” have rendered their collective verdict on a category of these investigational therapies—namely, 4 repurposed antiviral drugs: remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a—in an article published on December 2nd by the New England Journal of Medicine (NEJM).

And, perhaps in a surprise only to a handful of powerful political leaders globally, the consensus is that all 4 of these drugs “had little or no effect on hospitalized patients with COVID-19” in terms of overall mortality, need for mechanical ventilation, and duration of hospital stay.

“The currently available possible treatments do not provide a substantial benefit in reducing the important outcomes of mortality or need for mechanical ventilation,” Srinivas Murthy, MD, Associate Professor of Pediatrics, at the University of British Columbia in Vancouver and one of the researchers on the Solidarity Trial told Contagion®. “So, we need better treatments to be developed.”

When asked whether he saw the NEJM report as the “final word” on some of these drugs/regimens, Dr. Murthy’s response was unequivocal.

“Yes, four three of the drugs, this should be considered done,” he said.

The only exception being remdesivir, as the researchers are still randomizing patients “for the possibility of there being a small benefit on mortality,” according to Murthy.

Indeed, the findings of the Solidarity Trial are stark. For example, death occurred in 301 of 2,743 patients receiving remdesivir—the antiviral originally developed to treat Ebola—and in 303 of 2,708 who were given its control or placebo drug. Similarly, 104 of 947 study participants treated with the malaria drug hydroxychloroquine died, compared to 84 of the 906 given its corresponding control.

In all cases, barring interferon-beta-1a (209 vs 210), more patients taking the study drugs remdesivir (295 vs 284), hydroxychloroquine (75 vs 66), and the HIV drug lopinavir (126 vs 121) required mechanical ventilation compared to those given their respective controls. Drug treatment also did not reduce the length of time study patients were hospitalized.

In short, all these drugs are better designed for their original purposes—or at least perhaps in the cases of remdesivir—than they are for COVID-19. In fact, the findings of the Solidarity Trial, which included 11,330 patients treated at 405 hospitals in 30 countries (of whom, 1,253 unfortunately died while hospitalized with COVID-19), largely echo those of other, similar studies.

“[These findings] further solidify some of the earlier claims around treatments, and emphasizes the need for high-quality, generalizable data for these treatments,” Murthy said. “The importance of randomization, and embedding it within care as much as possible, will help us learn which treatments work, both during a pandemic, and after this pandemic is over.”