US biotech company Gilead Sciences has announced the start of two clinical Phase 3 trials to evaluate the safety and effectiveness of the investigational antiviral compound remdesivir in adults diagnosed with COVID-19. This progress follows the FDA’s rapid review and approval of Gilead’s investigational new drug (IND) filing.
The randomised, open-label, multicenter trials will enroll around 1,000 patients at medical centres mainly across Asian countries, and some other countries around the world with high numbers of confirmed Covid-19 cases, starting in March 2020. In addition to the standard of care, the first of two trials will examine the safety and effectiveness of both a 5-day and a 10-day dosing regimen of remdesivir for patients with severe COVID-19 symptoms. The second study will assess the safety and efficacy of the same dosing regimens of remdesivir in addition to standard of care for patients with moderate symptoms of COVID-19, compared with standard of care alone.
The investigational antiviral drug remdesivir
Remdesivir, which is not yet approved for use anywhere in the world, is an investigational nucleotide analog with a broad-spectrum antiviral activity.
Remdesivir has shown in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS, which are also coronaviruses (CoV) and are structurally similar to COVID-19. Remdesivir might potentially show activity against COVID-19, according to the indications of the limited preclinical data on remdesivir in MERS and SARS. However, Gilead does not have sufficient understanding of the effect of this medicine to warrant broad use at this time, because it is still an experimental drug that has only been used in a small number of patients with COVID-19 to date.
Currently, Gilead is outlining options for providing wider access to investigational remdesivir via suitable emergency channels should it demonstrate the prospect of being a safe and effective form of treatment based on the preliminary clinical study results. Gilead is also holding talks with regulatory agencies to determine the most efficient pathway for submitting remdesivir for approval for the treatment of COVID-19 in case the trial results are positive. The biopharmaceutical company is also in discussion with multiple organizations regarding the potential for future trials.
Compassionate use of remdesivir to COVID-19 patients for emergency treatment
In the absence of any approved treatment options, Gilead is collaborating with government and non-governmental organizations and regulatory authorities to provide remdesivir to COVID-19 patients for emergency treatment.
Requests for compassionate use must be sent by a doctor who is treating a patient. Gilead is monitoring and evaluating individual applications and requests that the patient is admitted to hospital with confirmed COVID-19 infection with significant clinical manifestations at a minimum. It is important to note that outcomes in individual cases of compassionate use are not enough to assess the efficacy and safety of remdesivir in COVID-19 care. This can only be established through prospective clinical trials.
Availability and Supply of Remdesivir
Remdesivir is currently in limited clinical supply but the biotech company is working to increase the availability of the experimental drug as quickly as possible. In response to the recent outbreaks of Ebola in West Africa, Gilead expanded the production of remdesivir to create an inventory of medication that could be used in response to potential pandemics, as well as a stockpile of materials used to manufacture.
Gilead has speeded up production schedules in anticipation of potential future demands to increase the supply available as quickly as possible. The antiviral drugs biotech is accelerating production even before knowing if remdesivir is determined to be safe and effective in treating COVID-19 patients.
In order to increase the available clinical supplies of remdesivir, Gilead is also developing two formulations of remdesivir in both liquid and freeze-dried forms, increasing its network of manufacturing partners to increase capacity and development, and has started internal remdesivir production to complement the ability of the external manufacturing network.
More about Gilead’s response to COVID-19
The American biotech company, which primarily focuses on antiviral drugs is working closely with the U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (DHHS), National Institute of Allergies and Infectious Diseases (NIAID) and Department of Defense (DoD) – CBRN Medical; the China CDC and National Medical Product Administration (NMPA); the World Health Organization (WHO), as well as and individual researchers and clinicians, to respond to the new coronavirus (COVID-19) outbreak through the appropriate experimental use of the investigational compound remdesivir.
The Chinese health authorities have conducted two clinical trials in patients infected with COVID-19 to assess the safety and effectiveness of remdesivir as a potential treatment for the novel coronavirus. Gilead is offering the study drug-free of charge and also provides guidance on study design and conduct. One research is testing remdesivir in patients with confirmed infections who have developed more serious clinical symptoms such as a supplemental oxygen requirement. The second trial evaluates remdesivir in patients with confirmed COVID-19 infection who have been hospitalised but do not show significant clinical manifestations of illness such as a requirement for oxygen. The research started enrolling patients with severe illness on the 6th of February. The research of moderate-illness patients started on February 13. Results from the clinical trials are expected in April. The U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has launched a Phase II adaptive, randomised, double-blind, placebo-controlled trial of remdesivir as a potential treatment for patients infected with COVID-19 in hospital.
Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences said,
“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. The speed with which remdesivir has moved into clinical development for this coronavirus reflects the pressing need for treatment options and the shared commitment of industry, governments, global health organizations and healthcare providers to respond to this public health threat with the highest urgency,”
Remdesivir’s replication in Taiwan
Meanwhile, Taiwan has worked on replicating the experimental Remdesivir drug from scratch. Last week on Thursday (Feb. 20), Academia Sinica announced scientists have successfully produced the drug at the milligram level with 97% purity. This week, National Health Research Institutes reached the gram milestone twice as fast as expected. Academia Sinica President James C. Liao hopes that the drug will not be needed in Taiwan but said it is important to have it at the ready in the event the outbreak worsens on the island, Taiwan News reports.
Chiung-Tong Chen, Ph.D. from the Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan:
“The active ingredient we produce could really become a drug to treat patients on a large scale. So for mass production, we’re talking about 1,000 times more artificial crystals. In addition, our vaccinology institute is working very hard to develop a vaccine. The National Health Research Institutes says it’s seeking corporate partners to launch the drug into test production at the 100-gram or kilogram level. Scientists say that with more work and testing, there could be a ray of hope on the deadly outbreak.”