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First glimpse of controlled remdesivir data cast doubt on its COVID-19 treatment potential

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After weeks of encouraging anecdotal and uncontrolled data for Gilead’s COVID-19 therapy remdesivir, the first hint of results from a placebo-controlled trial suggest that if the antiviral does provide a benefit, it may be closely correlated to treatment timing.

Data accidentally published to the World Health Organization’s website showed that a Phase III trial of remdesivir in patients with severe COVID-19 had a negative outcome.

Trading in shares of Gilead Sciences Inc. (NASDAQ:GILD) were briefly halted after falling sharply; the stock ended the day down $3.53 at $77.78 for a loss of $4.5 billion in market cap.

The Financial Times and STAT first reported on the results, which have since been removed from the WHO’s website. The trial was conducted in Hubei by the China-Japan Friendship Hospital.

The report concluded that remdesivir was not associated with clinical or virological benefits. The study summary suggested that after 28 days, the mortality rate for patients on remdesivir was 13.9%, compared with 12.8% for patients in the control group, according to a screen shot of the data published on STAT’s website.

“We believe the post included inappropriate characterizations of the study,” Gilead CMO Merdad Parsey said in a statement emailed to BioCentury. “Trends in the data suggest a potential benefit for remdesivir, particularly among patients treated early in disease.”

The potential for early treatment benefit was also highlighted in a note from Evercore ISI’s Umer Raffat. He pointed out that the Hubei study allowed patients to begin taking remdesivir up to 12 days after symptom onset, while patients in Gilead’s pair of Phase III studies took remdesivir within three days of a positive COVID-19 PCR test.

Anecdotal data from Gilead’s open-label trials had sent shares up to $83.99 on April 17, a move that added $9.4 billion to the biotech’s market cap. Comments from an investigator at the University of Chicago Medicine, a trial site for the Gilead studies, had suggested that most of the enrolled 125 patients had been discharged from the hospital (see “Next Inflection Points Comes into Focus for Gilead, Moderna”).

Timing is the most important driver of efficacy when it comes to antivirals treating acute infection, Raffat said. He said he continues to think remdesivir has activity “as long as patients take it early. But it’s not a silver bullet.”

Study size may also be a factor in the Hubei trial’s results.

The trial enrolled 237 patients with severe COVID-19; 158 patients received remdesivir and 79 served as controls. However, the study had been halted early due to low patient enrollment. A second Hubei trial in patients with mild-to-moderate disease has also ended early (see “Master Protocols on Deck”).

“Because this study was terminated early due to low enrollment, it was underpowered to enable statistically meaningful conclusions,” Parsey said. “As such, the study results are inconclusive.”

During a webinar hosted by CTTI Thursday, Ed Cox, VP of regulatory affairs at Regeneron Pharmaceutics Inc. (NASDAQ:REGN), highlighted the importance of randomization and sufficient trial size when trying to draw any conclusions about efficacy of COVID-19 therapies due to the wide variability in expected mortality rates under standard of care. The Clinical Trials Transformation Initiative is a public-private partnership between FDA and Duke University.

Gilead’s Phase III trial in patients with severe COVID-19, while open-label, will enroll 6,000 patients. Data are due this month.

NIH’s master protocol study has enrolled 900 patients in the remdesivir arm, above the target of 500. Data are expected next month.

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