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WHO restarts hydroxychloroquine testing as drug fails another COVID-19 trial

Editors flag ‘serious’ concerns regarding validity of data in Lancet paper

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In the latest hit to hydroxychloroquine, a double-blind, placebo-controlled study found that use of the malaria drug as post-exposure prophylaxis doesn’t prevent COVID-19. The report comes as the WHO resumes hydroxychloroquine testing in SOLIDARITY, and data from a trial that found an association with mortality have become suspect.

Reported Wednesday in The New England Journal of Medicine, researchers from the University of Minnesota, McGill University, the University of Alberta and the University of Manitoba tested whether the malaria drug could prevent either laboratory-confirmed COVID-19 or the development of symptoms consistent with COVID-19. The drug was given within four days of exposure to SARS-CoV-2.

The Phase III COVID-19 PEP trial was halted for futility on May 6 after a third interim analysis by an independent data safety monitoring board (DSMB). Outcomes, including hospitalizations, were patient-reported.

Among 821 asymptomatic participants with a median age of 40 years, 11.8% of hydroxychloroquine recipients and 14.3% of placebo recipients developed illness compatible with COVID-19 (95% CI: -7, 2.2; p=0.35) within 14 days.

A potential caveat is that treatment adherence was moderate and differed by cohort group: 75.4% of those receiving hydroxychloroquine took all their doses and 82.6% of those given placebo did so (p=0.01).

While the trial population differs from that of other reported studies -- hospitalized COVID-19 patients -- the study adds to the body of evidence suggesting that the malaria drug is not efficacious for treating the infection.

The report comes as FDA faces increasing pressure to rescind an Emergency Use Authorization for hydroxychloroquine and chloroquine to treat hospitalized COVID-19 patients (see “Hydroxychloroquine Testing Hahn’s, FDA’s Independence”).

But even as data stack up against the malaria drugs questions regarding its safety and efficacy linger.

On Wednesday, The Lancet issued an Expression of Concern regarding data published in a May 22 article that concluded hydroxychloroquine or chloroquine are associated with “decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.”

The journal’s editors said an independent audit of the source and validity of the data had been commissioned after “serious scientific questions” were brought to their attention. Results of the audit are expected “very shortly.”

Separately on Wednesday, the WHO said it is resuming testing of hydroxychloroquine in the SOLIDARITY trial after a data safety monitoring board (DSMB) found no reason to modify the trial protocol based on the available mortality data.

Citing The Lancet study, the WHO had paused SOLIDARITY’s hydroxychloroquine arm as a safety precaution while the DSMB reviewed trial data.

Real-world data

The National Center for Data to Health is using part of a $25 million NIH award to support the Oregon Health & Science University-based National COVID Cohort Collaborative to use real-world data (RWD). The NIH collaboration aims to develop treatments and predictive tools to mitigate the pandemic; about 60 clinical institutions have been invited to partner with HHS and clinical organizations to support data analysis.

At least 15 institutions including Johns Hopkins University, the University of North Carolina at Chapel Hill, Rockefeller University and Washington University have already agreed to participate.

RWD has already played a role in FDA granting Emergency Use Authorization to remdesivir from Gilead Sciences Inc. (NASDAQ:GILD) and hydroxychloroquine (see “The Pivotal Role of Real-World Data in a Pandemic” ).

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