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 June 2020, The Health Sciences Authority (HSA), in consultation with its Medicines Advisory Committee, granted conditional approval for remdesivir. As part of the conditional approval, Gilead is required to collect the relevant safety data and to monitor the use of remdesivir. HSA will also require data from ongoing clinical studies to be submitted post-approval to ensure the continued safety and efficacy of the product. Earlier in March 2020, HSA initiated an early access of remdesivir to COVID-19 patients in Singapore through the expeditious evaluation and approval of its use in clinical trials. Gilead filed for registration of remdesivir in Singapore in May 2020  .
In June 2020, the Taiwan Food and Drug Administration (TFDA) of the Ministry of Health and Welfare (MOHW) conditionally approved remdesivir for patients with severe SARS-CoV-2 infection, according to the Article 48-2 of Pharmaceutical Affairs Act, provided that the pharmaceutical company would implement a risk management plan (RMP) to ensure the safety after the importation. Earlier in May 2020, TFDA hold a meeting and invited pharmaceutical and clinical experts to discuss the application and approval requirements of remdesivir  .
In June 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency's (EMA) adopted a positive opinion recommending the granting a conditional marketing authorisation (CMA) to remdesivir for the treatment of COVID-2019 infections in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen. The company will have to submit the final reports of the remdesivir studies to the Agency by December 2020, and further data on the quality of the medicine, as well as the final data on mortality, by August 2020. The EMA received an application for CMA of remdesivir in June 2020 and formally started its evaluation. At the conclusion of the first cycle of the rolling review in May 2020, the CHMP invited the company to submit further data together with an application for a conditional marketing authorisation. Also, EMA’s committee for medicines for children (PDCO) has rapidly issued its opinion on the company’s paediatric investigation plan (PIP). Earlier, the CHMP started a rolling review of data on the use of remdesivir 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    .
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 June 2020, US FDA is revising fact sheet for health care providers to state that administration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir. However, US FDA is not aware of any instances of reduced activity occurring in clinical setting and it will continue to evaluate all the data related to remdesivir. The FDA has also revised the fact sheet for health care providers to clarify dosing and administration recommendations and to provide additional safety data and supporting data from clinical trials  .
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 May 2020, Roche in collaboration with Gilead Sciences initiated the phase III REMDACTA trial to evaluate the safety and efficacy of tocilizumab [see Adis Insight drug profile 800010359] 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, Europe and might expand to Brazil   .
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, Sunnybrook Health Sciences Centre initiated the phase II Canadian Arm of the SOLIDARITY Trial (CATCO) trial to evaluate the safety and efficacy of standard-of-care products plus remdesivir or hydroxycholoroquine or lopinavir/ritonavir (2114; NCT04330690). The adaptive, randomised, open-label, controlled clinical trial, in collaboration with countries around the world through the World Health Organization intends to enrol approximately 2900 patients in Canada  .
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, Luxembourg, Austria and will expand 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, the UK, Belgium, Canada, France, Germany, Italy, Israel, Netherlands, Romania, Spain, Switzerland, Australia, Austria, Cyprus, Croatia, Denmark, Estonia, Greece, Hungary, Ireland, Iceland, Czech Republic, Poland, Portugal, Slovakia and Slovenia (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. In April 2020, the company reported that the study was stopped in patients with severe symptoms due to delayed enrollment. However in June 2020, Gilead announce addition of expansion phase of the study was added to enroll up to 5 600 additional patients, including those on mechanical ventilation. 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. An expansion phase of the study was added to enrol up to 1 000 additional patients with moderate disease. Gilead Sciences has donated remdesivir and provided scientific input for these studies. In June 2020, Gilead Sciences release data from the trial     .
In February 2020, National Institute of Allergy and Infectious Diseases initiated the phase III ACTT-1 trial (Adaptive COVID-19 Treatment Trial) to evaluate the safety and efficacy of remdesivir for the treatment of COVID-2019 infections in patients (ACTT; 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. 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 June 2020, the EMA released the efficacy data from the trial     .
In May 2020, NIAID initiated the phase III trial to evaluate the safety and efficacy of remdesivir in combination with oral baricitinib, for the treatment of COVID-19 infections (20-0006 ACTT-II; NCT04401579). The randomised, blinded, controlled trial intends to enrol 1032 patients in the US, Japan, South Korea, Mexico and Singapore    .
In June 2020, ViralClear Pharmaceuticals (BioSig's subsidiary) initiated a phase II trial to evaluate the efficacy and safety of merimepodib [see Adis Insight Drug profile 800008158] in combination with remdesivir in patients with COVID-19 infections (VC02-01; NCT04410354). The double blind, randomized trial initiated enrolment of 40 patients in USA. The first patient was dosed in June 2020   .
In February 2020, 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 vitro testing conducted by Gilead has demonstrated that remdesivir is active against the virus that causes COVID-19  .
In May 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency's (EMA) recommended expanding the compassionate use of 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)  .
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 (S-20-01; 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 October 2019, National Institute of Allergy and Infectious Diseases completed 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 was initiated in June 2016 and enrol approximately 30 patients in the Guinea 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  .