Fewer Wuhan Patients For Gilead Remdesivir Study: WHO
China Coronavirus Studies Surge
Executive Summary
In a shocking and revealing account, a primary investigator of the front-runner antiviral drug for the coronavirus in China expresses concerns over finding enough patients for the study Wuhan, the outbreak's epicenter.
While China has confirmed that coronavirus cases are dropping outside Wuhan and Hubei province, the numbers are now spiking outside China. One of the leading antiviral hopes for the spreading outbreak, Gilead Sciences Inc.’s remdesivir, is now in a Phase III study in Wuhan after being used to treat the first confirmed patient in the US with promising results.
Surprisingly, the Wuhan study with the drug has encountered challenges including finding enough patients to enroll, noted a World Health Organization delegation which has just returned from a field trip to the hard-hit city, with over 20,000 confirmed cases.
“One of the things that really struck me yesterday, I was speaking to a researcher, a Chinese researcher called Cao Bin…who is running one of the most important antiviral trials in Wuhan right now. When I asked him what challenges they are finding when trying to implement the trial, he said the single biggest one is recruiting new patients into the trial because of the drop in cases,” Bruce Aylward, head of the China-WHO joint delegation to China, told reporters at a 24 February press briefing in Beijing.
Cao, a respiratory specialist physician at the Wuhan China-Japan Friendship Hospital, is the primary investigator for the remdesivir study.
“And Cao Bin is having trouble recruiting patients not just because the numbers are falling but also because we’re doing lots of other studies with things that are less promising. We have got to start prioritizing enrollment into those things that may save lives and save them faster,” Aylward cautioned.
Surging Studies Competing For Patients
Indeed, clinical studies for various potential treatments for the SARS-CoV-2 coronavirus are surging and flooding hospitals in Wuhan and other parts of China, stirring up grave concerns among many medical experts.
There are now as many as 200 such trials ongoing in China, a five-fold jump from only 40 just two weeks ago. The sheer number means that not only are the studies competing for patients in a health system that has been stretched thin for weeks, but also they are taking over critical clinical resources from the few facilities that are still open but running with reduced capabilities.
The majority of the clinical trials it seems are for traditional Chinese medicines. There are roughly 80 ongoing studies for TCMs, which is being touted by the National Medical Products Administration as a sign of the rapid response from the sector. (Also see "China Uses Old To Fight New As Repurposed Drugs Take Coronavirus Role" - Scrip, 21 Feb, 2020.)
While some studies are observational or for diagnostics, as many as 139 are intervention trials. But many of these have only small patient numbers with just a dozen enrolled while one study, with a soybean water derivative for the treatment of COVID-19, has just two participants.
In a paper published in the China Journal of Epidemiology, local epidemiologists and physicians estimated that 800-1,000 patients are needed for each study. A small sample size is a sure factor to deem a study futile, the experts said: “The insufficient sample size is likely to lead to inconclusive results.”
Strategic Approach Needed
Because confirmed coronavirus cases continue to decline outside Wuhan and Hubei province, some studies in these areas face difficulties in recruitment, and the need is emerging to prioritize and more strictly review and approve clinical studies.
This could explain why Gilead is taking its remdesivir study global. The US drug maker is now recruiting patients across Asian medical centers for a Phase III trial, beginning in March. This will study two doses after a rapid review and approval from the US FDA; the antiviral will be given to 1,000 patients, including roughly 400 with severe symptoms and 600 with mild symptoms.
Gilead is donating remdesivir on a compassionate use basis and speed will be key, noted a company executive. “Gilead’s primary focus is on rapidly determining the safety and efficacy of remdesivir as a potential treatment for COVID-19, and this complementary array of studies helps to give us a more expansive breadth of data globally on the drug’s profile in a short amount of time,” said Merdad Parsey, the company's Chief Medical Officer.
The molecule seems to offer the most promise among all those in clinical studies in China, acknowledged the WHO expert. “There’s only one drug right now that we think may have real efficacy. And that’s remdesivir,” said Aylward.
(For our rolling coverage of the coronavirus outbreak, click here.)