In May 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency's (EMA) recommended expanding the compassionate use remdesivir for the treatment of patients with COVID-2019 infections.the compassionate use recommendations covered the treatment of hospitalised patients requiring supplemental oxygen, non-invasive ventilation, high-flow oxygen devices or ECMO (extracorporeal membrane oxygenation). Earlier in the same month, the CHMP started a rolling review of data on the use of remdesivir for the treatment of coronavirus infections-2019 (COVID-2019 infections). The CHMP’s decision to start the rolling review of remdesivir was based on preliminary results from the NIAID- ACTT study [see below], which suggested a beneficial effect of remdesivir in the treatment of hospitalised patients with mild-to-moderate or severe COVID-2019 infections. However, EMA has not yet evaluated the full study and it is too early to draw any conclusions regarding the benefit-risk balance of the medicine   .
In May 2020, Gilead Sciences announced that Japanese Ministry of Health (MHLW) has granted regulatory approval of Venklury® (remdesivir) as a treatment for COVID-2019 infections under an exceptional approval pathway. The approval was granted on the basis of clinical data obtained from the phase III SIMPLE trial (see below) and from Gilead's compassionate use program, that included patients from Japan  .
In May 2020, the US Food and Drug Administration (FDA) granted an emergency use authorization to remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 infections in adults and children  .
In May 2020, Roche in collaboration with Gilead Sciences initiated the phase III REMDACTA trial to evaluate the safety and efficacy of Actemra/RoActemra plus remdesivir, versus placebo plus remdesivir in hospitalised patients with severe COVID-19 pneumonia. The randomised, double-blind trial intends to enroll approximately 450 patients in the US, Canada and Europe  .
In April 2020, Gilead Sciences and University of Helsinki initiated the phase III SOLIDARITY Finland trial to assess the efficacy and safety of remdesivir and hydroxychloroquine compoared with standard of care in patients with COVID-2019 infections (EudraCT2020-001784-88; WHO-FIN-COVID-19). The main objective of the trial is to investigate effect on allcause in-hospital mortality compared to standard of care. The randomised trial intends to enrol approximately 664 patients in Finalnd  .
In March 2020, the US FDA granted orphan drug designation to remdesivir for the treatment of of COVID-2019 infections. However the status was withdrawn by the US FDA in the same month following submission of a request by Gilead to the US FDA to rescind the orphan drug designation    .
In March 2020, Institut National de la Santé Et de la Recherche Médicale (INSERM) and Gilead Sciences initiated the phase III DisCoVeRy trial to assess safety and efficacy of remdesivir and other therapeutics including hydroxychloroquine, lopinavir/ritonavir compared with standard of care (NCT04315948; C20-15; EudraCT2020-000936-23). The primary endpoint of study is to determine the percentage of patients reporting each severity rating on a 7-point ordinal scale in 15 days. The randomised, adaptive trial intends to enrol approximately 3300 patients in France and will expands to other parts of Europe   .
In March 2020, Gilead initiated an expanded access treatment protocol for remdesivir for the treatment of COVID-19 infections in the US, UK, Belgium, Canada, France, Germany, Italy, Israel, Netherlands, Romania, Spain, Switzerland (GS-US540-5821; EudraCT2020-001453-49; NCT04323761). In April 2020, Froedtert & the Medical College of Wisconsin granted an approval for the enrollment in the expanded access programme    .
In March 2020, the China-Japan Friendship Hospital, the Feinstein Institutes for Medical Research and Gilead Sciences initiated two phase III SIMPLE trials to evaluate the safety and efficacy of remdesivir for the treatment of COVID-2019 infections in China, as well as other Asian countries and other countries globally. The first trial of the programme will evaluate the safety and efficacy of both a 5-day and a 10-day dosing regimen of remdesivir administered intravenously in patients with severe manifestations of COVID-19 (NCT04292899; GS-US-540-5773; EudraCT2020-000841-15; SIMPLE-severe). The trial will recruit approximately 400 patients globally including Germany, Spain, Italy, the Netherlands, the UK, Sweden, the US, Hong Kong, South Korea, Singapore, China, Taiwan, France, Japan and Switzerland  . The patients will be randomized in a 1:1 ratio to receive remdesivir 200mg on day one, followed by remdesivir 100mg each day until day 5 or 10, in addition to standard of care. The primary objective of this study is to evaluate the effect of remdesivir, as measured by the normalization of fever and oxygen saturation [T < 36.6 C armpit, < 37.2 C oral, < 37.8 C rectal; and Sp02 > 94%, sustained for at least 24 hours through Day 14]. In April 2020, the company reported that the study was stopped in patients with severe symptoms due to delayed enrollment  . In April 2020, efficacy and safety data from the trial was released by Gilead Sciences  . In May 2020, Gilead announced that the data from the SIMPLE-Severe study support treatment of some patients for 5 days rather than 10 days, depending on clinical status  .
The second SIMPLE trial met its primary endpoint in April 2020 which is designed to evaluate the safety and efficacy of a 5-day and a 10-day dosing regimen of remdesivir administered intravenously in patients with moderate manifestations of COVID-19, compared with standard of care (NCT04292730; GS-US-540-5774; EudraCT2020-000842-32; SIMPLE-moderate) . The trial will recruit approximately 600 patients in Germany, Spain, Italy, the Netherlands, the UK, Sweden, the US, Hong Kong, Korea, Singapore, China and Taiwan  . The patients will be randomised in a 1:1:1 ratio to receive remdesivir 200mg on day one, followed by remdesivir 100mg in addition to standard of care each day until day 5 or 10, compared with standard of care alone. The primary objective of this study is to evaluate the effect of remdesivir, as measured by the proportion of participants in each group discharged by day 14. Gilead Sciences has donated remdesivir and provided scientific input for these studies   .
In February 2020, National Institute of Allergy and Infectious Diseases initiated the phase II ACTT trial (Adaptive COVID-19 Treatment Trial) to evaluate the safety and efficacy of remdesivir for the treatment of COVID-2019 infections in patients (20-0006; U1111-1249-9599; EudraCT2020-001052-18; NCT04280705). The randomised, double-blind, placebo-controlled trial intends to enrol approximately 394 hospitalised patients in the US  . Moreover, Gilead Sciences reported that remdesivir was purportedly used in treating the first case of 2019 novel coronavirus (2019-nCoV), in the US. There was no data for remdesivir displaying activity against 2019-nCoV, but data was available for other coronaviruses  . In April 2020, EvergreenHealth announced that it is preparing for the second arm of the trial, which will eliminate the placebo group and provide the study drug to all the patients to evaluate its effectiveness against the virus. Moreover, EvergreenHealth reported initial preliminary reports from the trial  . In May 2020, Gilead announced that the trial findings support the use of remdesivir with the largest benefit observed among individuals who required oxygen supplementation but were not mechanically ventilated  .
In May 2020, NIAID initiated the randomised, double-blind, controlled clinical trial to evaluate the safety and efficacy of remdesivir in combination with oral baricitinib, for the treatment of COVID-19 infections. Enrolment of hospitalised patients diagnosed with COVID-2019 infections has been initiated in this ACTT2 trial in the US and the trial may expand to Europe and Asia  .
In vitro testing conducted by Gilead has demonstrated that remdesivir is active against the virus that causes COVID-19  .
In April 2020, the USFDA granted emergency use authorisation (EUA) for remdesivir for the treatment of hospitalized patients with COVID-19 infections. The EUA allowed both 5-day and 10-day treatment durations based on the severity of disease  .
In April 2020, EMA’s human medicines committee (CHMP) gave recommendations for the compassionate use programmes of remdesivir for treatment of coronavirus infections (COVID-19) in the European Union. earlier, Estonia, Greece, the Netherlands and Romania requested an opinion from the CHMP on the conditions for early access to remdesivir through compassionate use could be given to patients with COVID‑19  .
Remdesivir is available through an expanded access programme conducted by U.S. Army Medical Research and Development Command for the treatment of COVID-2019 infections in the US (NCT04302766)  .
Gilead Sciences provided remdesivir for compassionate use to 2 patients, one a female patient in the Royal Free Hospital in London in October and one in Guinea the following month  .
Gilead Sciences is also providing remdesivir for compassionate use to patients with COVID-2019 infections for emergency treatment outside of ongoing clinical studies  .
In April 2020, Gilead Sciences released efficacy and safety data of remdesivir from compassionate use programme for COVID-2019 infections   . Gilead Sciences in April 2020, reported that intravenous infusion of remdesivir demonstrated clinical improvement in first 53 patients who received treatment in compassionate programme  .
Ebola virus infections
In August 2019, based on independent Data and Safety Monitoring Board’s (DSMB) recommendation, Ridgeback Biotherapeutics prematurely terminated the phase II/III PALM trial designed to assess the safety and effectiveness of mAb 114; REGN 3470/3471/3479 , porgaviximab and remdesivir separately in patients with Ebola virus infections (19-I-0003; NCT03719586). The open-label, randomised, controlled study initiated by Gilead Sciences and National Institute of Allergy and Infectious Diseases in October 2018 enrolled approximately 681 patients toward an enrollment goal of 725 in the US and Congo   .
In June 2016, National Institute of Allergy and Infectious Diseases initiated the phase II PREVAIL IV trial to assess the antiviral activity, safety and tolerability of remdesivir 100mg IV in male Ebola survivors with evidence of Ebola virus persistence (999916137; 16-I-N137; NCT02818582). The randomised 1:1, double-blind, parallel, placebo-controlled, two-phase (treatment and longer-term follow-up) trial will enrol approximately 120 patients in the US and Liberia. Longer-term clearance of Ebola virus will be assessed during the 5-month follow-up phase  .
Gilead initiated a phase I trial in healthy volunteers to evaluate the safety, tolerability and pharmacokinetics of remdesivir  .
In a monkey model of Ebola virus infections, remdesivir displayed efficacy as well as potential for broad-spectrum anti-filovirus activity with 100% survival of monkeys  .
Remdesivir has a broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple viral pathogens, including Ebola, Marburg, MERS and SARS  .