HONG KONG – Foster City, Calif.-based Gilead Sciences Inc., which is ramping up its COVID-19 candidate production and research and is donating 1.5 million doses for compassionate use, published results in The New England Journal of Medicine from a cohort analysis of 53 severe patients hospitalized with severe complications from COVID-19, showing a cumulative incidence of clinical improvement of 84% after 28 days of follow-up, according to Kaplan-Meier analysis.
In the study, the patients were treated with the investigational antiviral remdesivir on an individual compassionate use basis. Improvements here were defined as discharge from the hospital and/or at least a two-point improvement from baseline on a predefined six-point scale.
Though it looks promising, remdesivir is still an investigational agent that is not approved for any disease or indication just yet. The drug was originally created as an Ebola treatment.
“However, it has been studied in healthy volunteers and in people with Ebola virus infections,” Andrew Hexter, vice president and general manager of Gilead Sciences Asia, told BioWorld. “It has also demonstrated activity in preclinical models against other pathogens, such as MERS and SARS, which are also coronaviruses and are structurally similar to the virus that is causing COVID-19.”
The limited data in MERS and SARS indicate that remdesivir could have potential activity against the new coronavirus.
Gilead’s remdesivir is a nucleotide analogue that targets the viral RNA polymerase, an enzyme that starts the viral transcription process. Remdesivir is broken down in the body into the active metabolite remdesivir triphosphate, which is incorporated into the viral RNA, thereby preventing replication of the virus.
“On that basis, we are investigating remdesivir against the COVID-19 virus in order to establish or determine its safety and efficacy,” said Hexter.
The company will also be scaling up its manufacturing to provide 1.5 million doses of remdesivir at no cost. Those will be “made available to patients via clinical trials, compassionate use and expanded access programs globally,” said Hexter. “We are working with regulatory authorities to make remdesivir globally available and establishing an independent advisory committee to advise us on appropriate allocations.”
“Having a potential treatment in our hands comes with significant responsibility,” said Daniel O'Day, Gilead’s chairman and CEO Gilead. “Providing our existing supplies at no charge is the right thing to do, to facilitate access to patients as quickly as possible and in recognition of the public emergency posed by this pandemic.”
Besides pumping up production, Gilead is also supporting multiple clinical trials led by other organizations to evaluate the safety and efficacy of remdesivir as a potential treatment for COVID-19, including two studies conducted in Hubei Province, China.
But Gilead has since been told that a study in China in patients with severe disease was terminated early due to low enrollment. It is now awaiting the publication of data to enable an in-depth review of the results.
However, another study in China in patients with mild to moderate disease is ongoing.
“The first two clinical trials of remdesivir began enrolling patients in China in early to mid-February,” Hexter said. “These trials are being coordinated by the China-Japan Friendship Hospital. The World Health Organization [WHO] is also conducting global, multicenter studies [also known as Solidarity trial] that have more than 70 countries participating.”
Remdesivir is one of four treatments being studied in the Solidarity trial.
The French National Institute of Health and Medical Research is initiating a study evaluating remdesivir and other potential treatments using WHO's master protocol. The U.S. NIH’s National Institute of Allergy and Infectious Diseases is conducting its global trial with its first sites enrolling patients in the U.S. According to Hexter, Gilead is donating the drug and providing scientific input for those studies.
Gilead is also conducting two phase III trials on its own, known as SIMPLE. The multicenter trials include 12 sites in Asia in Hong Kong, Taiwan, South Korea and Singapore, with more than 120 patients enrolled as of April 14.
“We believe remdesivir could show benefit and clinical improvement; however, we cannot draw definitive conclusions from compassionate use data given the limitations (such as small sample size, lack of controls and randomization, and short follow-up periods),” wrote analysts from investment bank Suntrust Humphrey Robinson.
They are not the only ones to see potential in remdesivir.
In January, China’s Wuhan Institute of Virology of the Chinese Academy of Sciences filed a patent for commercial use of remdesivir in China. Gilead representatives have stated that the company is aware of the move and that it had filed patent applications for the compound and its uses against coronaviruses globally, including in China, in 2016.
China has also started restricting research on the origin of the novel coronavirus amid a dispute between the U.S. and itself over it.
A directive issued by the Chinese Ministry of Education’s science and technology department stated that research papers on the topic must be strictly and tightly managed. There will now be several layers of approvals before articles can be submitted to journals.