While research for a vaccine plods on, Gilead’s remdesivir is emerging as the best stopgap measure to halt the relentless march of COVID-19 across the globe.
by Shaun Tan Yi Jie
In early February 2020, Gilead Sciences collaborated with Beijing’s China-Japan Friendship Hospital to test remdesivir, its experimental drug for Ebola, on Wuhan COVID-19 patients in two phase III clinical trials. By the end of the month, three more were confirmed: the U.S. National Institute of Health announced the drug was undergoing human clinical trials in the country on 26 February 2020, and one day later Gilead itself launched two phase III studies of remdesivir across multiple countries.
The five phase III clinical trials set up at an unprecedented breakneck speed in pharmaceutical history underscore just how much the human race is banking on remdesivir to stop COVID-19. While remdesivir is not a coronavirus drug, it has been hailed by public health officials as the most promising therapy to date for treating the disease—and an effective treatment for those already sick could buy drug makers crucial time to develop vaccines should the virus become endemic to the world.
“There is only one drug right now that we think may have real efficacy and that’s remdesivir,” said World Health Organization assistant director-general Bruce Aylward in late February 2020.
Indicated in the table are the five phase III clinical trials set up to test Gilead’s remdesivir.
All studies are randomized, double-blinded, and placebo-controlled.
Remdesivir’s Rise to Prominence
“Gilead first learned of reports of unusual cases of a pneumonia-like illness in China in late December/early January,” recalled Venus Tsang, Senior Director of Public Affairs, Gilead Sciences Asia. “At that time, scientists did not know the pathogen involved. The Chinese authorities’ identification of the pathogen as a coronavirus triggered our efforts to determine whether remdesivir could play a role, given the in vitro and animal model data demonstrating remdesivir’s activity against similar coronaviruses. Since then, we have been working closely with U.S. and Chinese health authorities on efforts to study remdesivir in clinical trials and provide access to remdesivir for compassionate use.”
Indeed, one such compassionate use, where unapproved drugs can be given with U.S. Food and Drug Administration (FDA)’s approval under select circumstances outside of clinical trials, propelled remdesivir to the forefront of the war against COVID-19.
On 20 January 2020, the first known U.S. case of COVID-19 was admitted to Providence Regional Medical Center in Everett, Washington. Within a few days, the 35-year-old man – who had visited family in Wuhan – started experiencing shortness of breath and required oxygen support. An X-ray revealed pneumonia.
The hospital informed the U.S. Centers for Disease Control, which suggested trying an experimental drug, and mentioned Gilead’s remdesivir. Hospital officials got in touch with Gilead about providing the drug, and then got the approval from FDA to treat the patient under the compassionate use program. Gilead overnighted the drug to the hospital.
“Treatment with intravenous remdesivir was initiated on the evening of the seventh day, and no adverse events were observed,” the medical team wrote in a case report in the New England Journal of Medicine. The man started feeling better the following day.
How Does It Work?
The apparent success in one patient does not prove the drug is effective, and that is where the five large-scale trials come in. According to Tsang, remdesivir has been able to advance into clinical studies so quickly for two key reasons. Firstly, it had a large body of preclinical evidence that indicated it could temper coronavirus infections. “While there are no antiviral data for remdesivir that show activity against COVID-19 at this time, available data in other coronaviruses give us hope,” said Tsang. “Remdesivir has demonstrated in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS, which are coronaviruses that are structurally similar to COVID-19.”
Secondly, thanks to its use in Ebola, it was known to be generally safe in humans. “We have been able to leapfrog Phase II studies of remdesivir in coronavirus because of the available safety data from studies in Ebola virus as well as the WHO compassionate use program with remdesivir for Ebola,” Tsang told APBN.
But if remdesivir was tried for Ebola treatment, how can it also work against coronaviruses? Apparently, the key feature of remdesivir is that it is a “nucleotide analog”, Tsang describes, meaning it mimics the appearance of a real nucleotide – in this case adenosine. This causes RNA polymerase – the enzyme that the virus uses to replicate itself – to pick it up instead of the real adenosine and insert it into the strand of viral genome that is being constructed. Once in place, remdesivir acts as a roadblock, preventing any additional pieces from being strung on. This leaves the strand short of the full genome, and replication is halted.
Remdesivir can inhibit coronaviruses as well as Ebola in this way because the viruses’ polymerases are similar enough. The drug does not appear to work on other viruses with more unrelated forms of polymerase.
Patent Complications
While remdesivir fast-tracks in hospitals around the world, it seems to be hitting a few snags in the legal arena. On 21 January 2020, it was reported that Wuhan Institute of Virology of the Chinese Academy of Sciences filed a patent for commercial use of remdesivir in China. They sought to secure this patent “out of national interest”, and some believe this move by the Institute may enable China to avoid having to pay steep licensing fees for using the patented drug.
However, the China National Intellectual Property Administration revealed that Gilead has applied for eight patents on the drug, three of which already have been approved, while the other five are being reviewed. Tsang further disclosed to APBN that their patents were filed way back in 2016.
“Presently, the patent application for the uses against coronavirus is still pending in China,” said Tsang. “We are aware of reports of the Wuhan Institute for Virology’s patent application. Gilead has no influence over whether a patent office issues a patent to the Chinese researchers. Their application has been filed more than three years after Gilead’s filing and will be considered in view of what is already known about the compound and pending patent applications. We are unable to comment on details of the researchers’ patent application because there is an 18-month delay for an application to be published.”
To add fuel to fire, a Suzhou pharmaceutical firm BrightGene claimed on 12 February 2020 to have successfully copied remdesivir. It said it had already mass-produced the active ingredient and is in the process of turning the drug into finished doses. A spokesman for the company argued that there was no patent infringement issue because it was not selling the product.
In a further twist, the Shanghai Stock Exchange announced on 2 March 2020 that BrightGene had not gained approval from China’s drug regulator, nor Gilead, to make remdesivir. The company has also not obtained the relevant qualifications for mass production of the therapy, said the stock exchange.
It appears that remdesivir’s road ahead on the legal front will not be as straightforward. Nevertheless, Gilead is clear where its priorities lie at the moment. “Our focus at this time is on rapidly determining the potential for remdesivir as a treatment for COVID-19 and accelerating manufacturing in anticipation of potential future supply needs,” Tsang stressed. [APBN]
About the Interviewee
Venus Tsang, Senior Director, Public Affairs, Gilead