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1119 WHO recs against Veklury EMB nov19 4pm PT
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Regulation

WHO counters FDA as it recommends against Veklury for COVID-19

Nov 20, 2020 | 12:28 AM GMT

The WHO’s new guidance counters FDA’s October approval of Gilead’s Veklury for hospitalized patients, adding to the debate around the drug’s use and variable performance in randomized, controlled trials.

In The BMJ on Thursday, the WHO issued a “weak or conditional recommendation against” treating hospitalized COVID-19 patients with Veklury remdesivir from Gilead Sciences Inc. (NASDAQ:GILD).

In a statement shared with BioCentury, Gilead said, “Veklury is recognized as a standard of care” for hospitalized patients by “numerous credible national organizations” including NIH’s National Institute of Allergy and Infectious Diseases (NIAID), Japan, the U.K. and Germany. The support is based on data from randomized, controlled studies showing “the clinical benefits of Veklury, such as significantly faster recovery, which can free up limited hospital resources.”

The company added, “We are disappointed the WHO guidelines appear to ignore this evidence at a time when cases are dramatically increasing around the world and doctors are relying on Veklury as the first and only approved antiviral treatment.”

The WHO’s latest guidance, which reverses a weak recommendation issued in the first version of the guidelines to treat severe COVID-19 with Veklury, was triggered by data from the WHO’s SOLIDARITY master protocol study released in mid-October. The results showed Veklury did not reduce 28-day mortality, initiation of ventilation or duration of hospitalization. 

The recommendation, informed by a 28-member panel, was based on a meta-analysis of pooled data from SOLIDARITY and three trials: NIH’s ACTT-1 adaptive master protocol study, Gilead’s open-label SIMPLE-Moderate trial and a Chinese Phase III study for which data were reported in The Lancet in April. The WHO said the panel found a lack of evidence for improved outcomes that matter to patients such as reduced mortality, need for mechanical ventilation and time to clinical improvement.

In Thursday’s statement, Gilead noted “the WHO preprint manuscript report a trend toward the reduction of death rates in the remdesivir group for patients on supplemental oxygen,” and added that Veklury led to a significant reduction in mortality when the publicly available SOLIDARITY data were analyzed “using a conventional 95% CI” versus the 99% CI used by the WHO. 

The WHO’s guidelines and underlying rational largely contradict the justifications FDA provided when it approved Veklury on Oct. 22.

FDA cited data from ACTT-1, and supportive evidence from SIMPLE-Moderate and SIMPLE-Severe. In contrast with SOLIDARITY, ACTT-1 showed the compound reduced time to recovery from 18 to 11 days as well as the incidence of new mechanical ventilation or ECMO.

However, no randomized controlled trial has demonstrated a survival benefit for the antiviral. 

Still, former FDA commissioner Scott Gottlieb told BioCentury when FDA approved Veklury that he thinks the magnitude of the crisis means regulators can’t hold out for home runs. “We need to accept singles and doubles when it comes to developing treatments for COVID-19, given the scope of the crisis, and how quickly we’ve moved treatments into development,” said Gottlieb. “Based on the available evidence, remdesivir looks like a solid single, and maybe in time better. That can be meaningful for patients.”

Shortly before the WHO’s new guideline became public, FDA issued an emergency use authorization (EUA) to Eli Lilly and Co. (NYSE:LLY) for Olumiant baricitinib in combination with Veklury to treat hospitalized COVID-19 patients ages two and older who requiring supplemental oxygen, invasive mechanical ventilation or ECMO.

The EUA is based on data from NIH’s ACTT-2 trial, which showed the oral JAK-1/JAK-2 inhibitor reduced time to recovery by about one day when added to Veklury.

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