As efforts to develop an effective vaccine for COVID-19 continue, in parallel, drug developers are investigating the effectiveness of existing drugs at treating patients with COVID-19. The investigational antiviral drug remdesivir has been explored as a treatment for several indications, including Ebola, severe acute respiratory syndrome (SARS), Marburg, Middle East respiratory syndrome (MERS) – and most recently COVID-19.
The US Food and Drug Administration (FDA) recently approved Gilead’s request to conduct clinical trials to investigate the use of an inhaled formulation of remdesivir as a treatment for COVID-19. Screening of healthy volunteers for a Phase 1 study is set to begin this week (June 22, 2020) with the aim to begin studies in COVID-19 patients in August 2020.
“Remdesivir, our investigational antiviral medicine, is currently given to patients intravenously through daily infusions in the hospital. An inhaled formulation would be given through a nebulizer, which could potentially allow for easier administration outside the hospital, at earlier stages of disease,” – Daniel O’Day, Chairman & CEO, Gilead Sciences.In light of this announcement, we take a closer look at remdesivir, the clinical research that has been conducted so far, and the future trials Gilead has planned in relation to COVID-19.
What is remdesivir?
Remdesivir is an antiviral medication that is being investigated in several ongoing international clinical studies. It is a nucleotide analog with broad-spectrum antiviral activity, that is thought to inhibit the action of RNA polymerase. By incorporating into RNA, additional nucleotides cannot be added, resulting in the termination of RNA transcription. Remdesivir has been previously investigated in humans with Ebola and has shown promise in animal models of MERS and SARS, both closely related to the 2019 novel coronavirus, SARS-CoV-2.
Remdesivir studies so far
On May 1, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for remdesivir for the treatment of hospitalized patients with severe COVID-19. This authorization allows healthcare providers to administer the drug intravenously, to treat hospitalized COVID-19 patients diagnosed with severe disease*. Remdesivir has not received regulatory approval from the FDA for any indication including COVID-19.
On May 22, 2020, preliminary results were published in The New England Journal of Medicine, indicating that intravenous remdesivir was superior to the standard of care for the treatment of adults hospitalized with COVID-19 with evidence of lower respiratory tract infection. The preliminary report was based on data obtained from the Adaptive COVID-19 Treatment Trial (ACTT), a double-blind, randomized, placebo-controlled trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). Overall, remdesivir-treated patients recovered after 11 days – four days faster than those administered placebo.
A second NIAID study, called ACTT2, was launched at the beginning of May to investigate the safety and efficacy of remdesivir plus the anti-inflammatory drug baricitinib as a treatment for hospitalized adults diagnosed with COVID-19. It is an adaptive randomized double-blind placebo-controlled multi-center trial. Eligible study participants will be randomly assigned 1:1 to the following treatment arms:
- Arm 1: study participants receive baricitinib tablets orally and intravenous remdesivir
- Arm 2: study participants receive placebo tablets orally and intravenous remdesivir
“We now have three randomized, controlled clinical trials demonstrating that remdesivir improved clinical outcomes by several different measures,” – Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences.In addition to the NIAID sponsored studies, Gilead is also conducting its own studies, referred to as “SIMPLE trials”. The first SIMPLE study investigated the safety and efficacy of 5- and 10-day dosing durations of intravenous remdesivir in hospitalized patients with severe COVID-19. Topline results were announced on April 29 and full study data were published in The New England Journal of Medicine on May 27, 2020. The trial showed no significant difference between a 5-day course and a 10-day course of remdesivir in those with severe COVID-19 (not requiring mechanical ventilation).
On June 1, 2020, Gilead announced topline results from the second Phase 3 SIMPLE study. The study demonstrated that patients in the 5-day remdesivir group were 65% more likely to have a clinical improvement at Day 11, compared with those in the standard-of-care group.
Gilead has teamed up with Genetech (a member of the Roche group) to initiate a global Phase 3, randomized, double-blind, multicenter trial called “REMDACTA” to investigate the safety and efficacy of remdesivir plus Actemra® (tocilizumab) versus remdesivir plus placebo, in hospitalized patients with severe COVID-19 pneumonia.
Gilead is now exploring the use of remdesivir in the earlier stages of the disease, with hopes that it may be possible to help stop progression of COVID-19, resulting in less patients requiring hospitalization.
“As part of our next wave of clinical development, we will study remdesivir in treating earlier in the disease, in combination with other therapies and in additional patient groups,” – Daniel O’Day, Chairman & CEO, Gilead Sciences.The company is also exploring the use of remdesivir in combination with other therapeutics, with an aim to improve patient outcomes.
Daniel O’Day explains in his open letter that in the coming months the results will be available from two studies exploring complementary approaches – the use of remdesivir in combination with baricitinib and the used of remdesivir with tocilizumab.
In addition to extending their focus to earlier treatment and combined treatment strategies, Gilead will also be conducting studies of remdesivir in vulnerable patient populations.
“Last week, we announced that we are about to begin a clinical trial for children. The study will treat approximately 50 children, from newborns to adolescents who are hospitalized with COVID-19. We are also collaborating with an external group on a study in pregnant women, and we are planning a trial for patients with end-stage renal disease,"
"Our continued aim in all our studies is to reflect the diverse demographics of the communities affected, including factors such as race, ethnicity and gender.” – Daniel O’Day, Chairman & CEO, Gilead Sciences.
*Severe disease is defined as patients with an oxygen saturation ≤ 94% on room air or requiring supplemental oxygen, or requiring mechanical ventilation, or requiring extracorporeal membrane oxygenation.