ViewPoints: Gilead takes issue with remdesivir’s ‘flop’ in Chinese Phase III trial

Gilead Sciences may have some relevant arguments about why newly reported Phase III results for remdesivir in severe COVID-19 patients was not the flop that researchers described it as, but the readout adds another clue pointing towards modest efficacy and a narrow therapeutic window.

The backstory

Clinicians, investors and the general public alike are scouring every drip and drab of new data from ongoing trial looking for hints about whether a possible treatment for COVID-19 may be in the offing. Last week, anecdotes about an encouraging efficacy signal that leaked out from a single site participating in a Gilead-sponsored study and touched off a cascade of optimistic stories and a big jump in the company’s shares. (See ViewPoints: Optimism accumulates well ahead of COVID-19 progress.)

What happened

On April 23, the World Health Organisation (WHO) accidentally published a draft report from a Chinese Phase III trial in which intravenous remdesivir was said to have “flopped” as a treatment for severe COVID-19. The document went on to suggest that Gilead’s agent failed to improve the condition of patients and was not found to reduce viral load, and in fact a higher percentage of those in the experimental arm died (13.9% versus 12.8% for control).

The study enrolled 237 subjects, including 158 who were given remdesivir while the other 79 were observed as controls. Researchers noted that 18 of those receiving the experimental therapy had to discontinue therapy due to side effects.

What matters most

The WHO took the post down soon after a Financial Times posted an article referencing it, and the organisation issued a statement saying the draft report had been “inadvertently posted on [our] website” despite still undergoing the peer review process.

Gilead was quick to issue a statement of its own refuting suggestions that remdesivir had failed. To the contrary, the company argued, characterising the study as a failure would be “inappropriate” because it was terminated early due to low enrolment, meaning it was “underpowered to enable statistically meaningful conclusions.”

Evercore ISI analyst Umer Raffat cast doubt about the usefulness of drawing inferences about remdesivir from the full dataset of this particular study – even once they have been fully vetted – because patients were enrolled into the treatment arm up to 12 days after COVID-19 symptoms emerged. He believes this is far too large a window.

“This point on exact timing of starting remdesivir is key. It’s the most important driver of efficacy. In fact, this is a principle in antivirals for acute infection: the earlier you start, the better the efficacy (this is also true for Tamiflu - you have start in less than 48 hours for flu),” he remarked.

The bigger picture

Questions remain about remdesivir’s commercial prospects even if it proves successful in clinical trials, however, The Street is nevertheless hanging on every update.

Indeed, Gilead shares jumped as much as 16% on April 17 based on a report of rapid recoveries of patients treated with remdesivir in a pair of uncontrolled trials. In contrast, the errant WHO post had a similar but opposite effect, sending the company’s market cap sliding as much as 6% in afternoon trading before closing the day down 4%.

There are plenty of reasons to take both reports – the positive anecdotes from last week and this week’s premature readout – with several grains of salt. Firm conclusions must wait for data from one or more of the handful of randomised and controlled clinical trials that remain ongoing.

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