Gilead Sciences’ headquarters in Foster City, California
PME talks to Julian Cole, Senior Director, Medical Affairs at Gilead Sciences about the impact of the COVID-19 epidemic, the company’s efforts to find an effective drug treatment for patients and the journey of remdesivir that began a decade ago as part of Gilead’s emerging viruses programme.
In May, remdesivir was granted an emergency use authorisation (EUA) for use in patients hospitalised with SARS-CoV-2, the virus which causes COVID-19. What were the trial results that led to this EUA?
An EUA is a mechanism through which the Food and Drug Administration (FDA) can approve the temporary use of an investigational medicine
to contribute to the medical response in public health emergencies.
The EUA was based on then available data from two global clinical trials – the National Institute for Allergy and Infectious Diseases’ (NIAID) placebo-controlled phase 3 study in patients with moderate to severe symptoms of COVID-19, including those who were critically ill, and Gilead’s global phase 3 study (SIMPLE Trials) evaluating five-day and ten-day dosing durations of remdesivir in patients with severe disease.
NIAID’s Adaptive COVID-19 Treatment Trial (ACTT-1) showed that remdesivir + Standard of Care (SOC) significantly shortened time to recovery, provided greater clinical improvement and also reduced disease progression compared with placebo + SOC. The results of Gilead’s SIMPLE Trials showed that a shorter, five-day dosing regimen of remdesivir provided similar efficacy and safety as a ten-day treatment course.
The FDA has approved remdesivir under the brand name Veklury for the treatment of hospitalised COVID-19 patients and remdesivir was the first treatment approved for COVID-19 in the US. What are the specific challenges of getting scientific consensus during a rapidly developing drug process in the midst of a global pandemic?
COVID-19 has thrown the importance of clinical trials into the spotlight, along with the need for vaccines and treatments to protect human health, and the role of the global pharmaceutical industry in producing them. It also brought attention to the fact that not all clinical trials are the same in terms of design, methodology, etc, and different trials are needed to help us assess safety and efficacy of medicines when they are developed, a process that takes several years. In the context of a global pandemic, this timeline was reduced to months.
At Gilead, we have spent more than 30 years investigating viral diseases. Virologists have long recognised that the biggest viral threat to human health would come from a virus which didn’t yet exist in humans. We have an emerging viruses programme that is dedicated to developing a large library of antiviral medicines that can be quickly taken off the shelf and tested in the event of a global health emergency in order to streamline the trial process.
Remdesivir was developed a decade ago as part of this commitment, and as soon as we heard reports from China that a new virus posed a significant threat to humans, we moved as quickly as possible to test whether it could have potential against this particular virus – which was consequently identified as SARS-CoV-2 – first in the laboratory, then in animal models and finally in humans.
To further speed up the trial process, we donated our entire stock of remdesivir and placebo to different global trials with different study designs, investigating candidate treatments across the world, while we worked to increase our own and partners’ manufacturing capabilities to build capacity for ongoing global supply. We continue to invest in evaluating ways to enhance outcomes with remdesivir, extend treatment to more groups of patients and ensure we are ready for future pandemics.
The World Health Organization (WHO) has not included Gilead’s antiviral treatment remdesivir in a COVID-19 drug scheme aimed at supplying treatments to developing countries. When the WHO published results from its own study of remdesivir, it said the results showed that the drug had ‘little effect’ on COVID-19-associated mortality. How does Gilead explain the results from this study?
The Solidarity trial design prioritised access to remdesivir and other investigational treatments in around 30 countries across the world. This was a noble and ambitious approach, but in this context, the WHO had to make choices. As it enrolled a large number of patients across different countries, many of which have different healthcare systems, there was a large variability in the implementation of the study, SOC controls and patient populations across trial sites. This meant it was difficult to have rigorous collection of data and, therefore, draw definitive conclusions.
However, the data from the Solidarity trial does not negate other study results – particularly from a trial designed with the strictest of scientific standards and rigorous data collection, as is the case with ACTT-1. Post hoc analysis of the ACTT-1 study notes a reduction in mortality in patients on remdesivir and low flow oxygen support.
The WHO study cannot counter this point since it did not report data from this subgroup of patients. This is not a problem, and it should be emphasised that the WHO data advances science, but the methods are different, and the results are neither opposed nor comparable.
In response to the WHO study, a Gilead spokesperson said that there was “more robust evidence from multiple randomised, controlled studies published in peer-reviewed journals validating the clinical benefit of remdesivir”. Can you offer more details about the studies published in the aforementioned peer-reviewed journals?
Remdesivir has been assessed in different randomised, controlled clinical trials, including a randomised, double-blind, placebo-controlled clinical trial (ACTT-1) – the gold standard for evaluating the efficacy and safety of investigational drugs.
The results from the NIAID’s ACTT-1 trial, which was conducted primarily in the United States and Europe, found that remdesivir + SOC significantly shortened time to recovery, provided greater clinical improvement and also reduced disease progression compared with placebo + SOC. This data was peer-reviewed and published in the New England Journal of Medicine.
The SIMPLE-Severe trial was an open-label clinical trial that evaluated the safety and efficacy of both a five-day and a ten-day dosing regimen of remdesivir administered intravenously in patients with severe manifestations of COVID-19.
The data was peer-reviewed and published in NEJM. The SIMPLE-Moderate trial was a randomised open-label clinical trial that evaluated the safety and efficacy of a 5-day and a 10-day dosing regimen of remdesivir administered intravenously versus standard of care in patients with moderate manifestations of COVID-19. The data was peer-reviewed and published in the Journal of the American Medical Association (JAMA).
Lastly, the two randomised, double-blind, placebo controlled clinical trials were conducted at multiple sites in Hubei province, China, where the infection was first described. They were coordinated by the China-Japan Friendship Hospital in Beijing. The results from the severe study was published in The Lancet.
The European Commission has signed a joint procurement agreement for Gilead’s COVID-19 antiviral treatment remdesivir. How does pricing for the drug in the EU compare to pricing in the US?
In light of the extraordinary medical needs during this pandemic, we have set a single global government price in developed countries. The majority of patients will take a five-day treatment course. In developed countries, the price of a five-day treatment course is $2,340. The single government price in the developed world aimed to remove the need for lengthy reimbursement processes in each country which resulted to almost simultaneous access for patients around the world.
Although the price is significantly lower than the value the medicine represents for healthcare systems, this was the best way to prioritise speed of access for patients – making it an approach worthy of consideration for future global healthcare emergencies.
Previously, countries across the EU have reported issues with procuring sufficient supplies of remdesivir after the US bought most of the global stock earlier this year. What steps are being taken with regard to manufacturing and distribution to ensure that sufficient supplies remain available to meet demand?
Since January, Gilead has taken multiple steps to ramp up production and rapidly build supply in recognition of the lengthy manufacturing timeline. In addition to process improvements that have shortened the manufacturing timeline to six months, Gilead has expanded its global network of both internal manufacturing sites and external organisations, including partnering with industry peers, to add manufacturing capacity around the world. Our manufacturing network now includes more than 40 companies in North America, Europe and Asia.
By working together in a coordinated fashion, this network of partners is supporting us to meet global patient needs. We have increased supply more than 50-fold since January 2020 and have been able to meet real-time global demand since October 2020. By the end of 2020 we expect to have produced more than two million treatment courses, and we anticipate producing several million more in 2021, if needed.
Beyond this network, in the developing world, we have entered into non-exclusive voluntary licensing agreements with nine generic manufacturers to further expand access and supply of remdesivir. These agreements are royalty-free during the pandemic and our hope is that it will help serve 127 countries classified as lower-income or that face significant obstacles to healthcare access.
Gilead Sciences is an American biopharmaceutical company headquartered in Foster City, California that researches, develops and commercialises drugs, with a goal to ‘discover, develop and commercialise therapeutics that transform care for people around the world’