Remdesivir - Knowledge

1471:(CHMP) of the EMA recommended expanding the compassionate use of remdesivir to those not on mechanical ventilation. In addition to those undergoing invasive mechanical ventilation, the compassionate use recommendations cover the treatment of hospitalized individuals requiring supplemental oxygen, non-invasive ventilation, high-flow oxygen devices or ECMO (extracorporeal membrane oxygenation). The updated recommendations were based on preliminary results from the NIAID-ACTT study, which suggested a beneficial effect of remdesivir in the treatment of hospitalized individuals with severe COVID‑19. In addition, a treatment duration of five days was introduced alongside the longer ten-day course, based on preliminary results from another study (GS-US-540-5773) suggesting that for those not requiring mechanical ventilation or ECMO, the treatment course may be shortened from ten to five days without any loss of efficacy. Individuals who receive a five-day treatment course but do not show clinical improvement will be eligible to continue receiving remdesivir for an additional five days. 1677:) contract with Gilead, to make the drug available there in early August 2020. In October 2020, Gilead Sciences and the European Commission announced they had signed a joint procurement framework contract in which Gilead agreed to provide up to 500,000 remdesivir treatment courses over the next six months to 37 European countries. Among the contracting countries were all 27 EU member states plus the United Kingdom, "Albania, Bosnia & Herzegovina, Iceland, Kosovo, Montenegro, North Macedonia, Norway, and Serbia". At the time, the price per treatment course was not disclosed; Reuters reported the price was 2,070 euros, thereby implying the total value of the contract (if all 500,000 courses are ordered) is approximately €1.035 billion. Under the contract, each participating country will directly place orders with Gilead and pay Gilead directly for its own orders. 40: 1630:(FDA) in October 2020, for use in adults and children twelve years and older requiring hospitalization for treatment of severe COVID‑19 infections. In January 2022, the FDA gave regulatory approval to remdesivir for use in adults and children (twelve years of age and older who weigh at least 40 kilograms (88 lb) and are positive for COVID‑19, not hospitalized, and are ill with COVID‑19 having high risk for developing severe COVID‑19, including hospitalization or death. In April 2022, the FDA expanded the approval of remdesivir to include people 28 days of age and older weighing at least 3 kilograms (6.6 lb). 1386:(FDA). The approval by the FDA does not include the entire population that had been authorized to use remdesivir under an Emergency Use Authorization (EUA) originally issued in May 2020. In order to ensure continued access to the pediatric population previously covered under the EUA, the FDA revised the EUA for remdesivir to authorize the drug's use for treatment of suspected or laboratory-confirmed COVID‑19 in hospitalized pediatric patients weighing 3.5 kilograms (7.7 lb) to less than 40 kilograms (88 lb) or hospitalized pediatric patients less than twelve years of age weighing at least 3.5 kilograms (7.7 lb). 1603:

courses. Absent from these announcements was any discussion of allocation of remdesivir production to the approximately 70 countries omitted from Gilead's generic drug licensing agreements—including much of Europe and countries as populous as Brazil, China, and Mexico—or the 127 countries listed on those agreements (during the time it will take for Gilead's generic licensees to ramp up their own production). As the implications of this began to sink in, several countries publicly confirmed the next day that they already had adequate supplies of remdesivir to cover current needs, including Australia, Germany, and the United Kingdom.

1081:. Two hours post injection, the main metabolite GS-441524 is present at micromolar concentrations, whilst intact Remdesivir is no longer detectable. Because of this rapid extracellular conversion to the nucleoside GS-441524, some researchers have questioned whether the active nucleotide triphosphate is truly derived from Remdesivir pro-drug removal or whether it occurs by GS-441524 phosphorylation, and whether direct administration of GS-441524 would constitute a cheaper and easier to administer COVID‑19 drug compared to Remdesivir. The activated nucleotide triphosphate form has sustained intracellular levels in 8050: 608: 585: 1831:(FDA) approved remdesivir based on the agency's analysis of data from three randomized, controlled clinical trials that included participants hospitalized with mild-to-severe COVID‑19. The FDA granted approval and reissued the revised EUA to Gilead Sciences Inc. The FDA approved remdesivir based primarily on evidence from three clinical trials (NCT04280705, NCT04292899, and NCT04292730) of 2043 hospitalized participants with COVID‑19. The trials were conducted at 226 sites in 17 countries including the United States. 1061:. Unlike with many other chain terminators, this is not mediated by preventing addition of the immediately subsequent nucleotide, but is instead delayed, occurring after five additional bases have been added to the growing RNA chain. For the RNA-Dependent RNA Polymerase of MERS-CoV, SARS-CoV-1, and SARS-CoV-2, arrest of RNA synthesis occurs after incorporation of three additional nucleotides. Hence, remdesivir is classified as a direct-acting antiviral agent that works as a delayed chain terminator. 1177: 970: 1569:(ECMO), a heart–lung bypass machine. Distribution of remdesivir under the EUA was controlled by the US government for use consistent with the terms and conditions of the EUA. Gilead supplied remdesivir to authorized distributors, or directly to a US government agency, who distributed it to hospitals and other healthcare facilities as directed by the US government, in collaboration with state and local government authorities, as needed. Gilead stated they were donating 1.5 6542: 3707: 6561: 4908: 7243: 3726: 31: 8038: 8026: 4916: 7047: 7001: 6006: 5932: 5879: 5835: 5703: 4825: 4755: 4676: 4379: 4322: 4130: 3685: 3106: 2967: 2914: 2871: 2831: 1349:) with remdesivir at a 30:1 ratio. Since that implies an enormous amount of Captisol is needed to stabilize and deliver remdesivir (on top of amounts needed for several other drugs for which the excipient is already in regular use), Ligand announced that it is trying to boost Captisol annual manufacturing capacity to as much as 500 metric tons. 1565:(EUA) for remdesivir to be distributed and used by licensed healthcare providers to treat adults and children hospitalized with severe COVID‑19. Severe COVID‑19 is defined as patients with an oxygen saturation (SpO2) <= 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring 1787:. Travis Warren, who has been a USAMRIID principal investigator since 2007, said that the "work is a result of the continuing collaboration between USAMRIID and Gilead Sciences". The "initial screening" of the "Gilead Sciences compound library to find molecules with promising antiviral activity" was performed by scientists at the 1553:

confirmed the statement at the same press conference. It was later revealed that Gilead had been providing remdesivir in response to compassionate use requests since 25 January. On 23 March 2020, Gilead voluntarily suspended access for compassionate use (excepting cases of critically ill children and

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companies in India and Pakistan to manufacture remdesivir for distribution to 127 countries. The agreements were structured so that the licensees can set their own prices and will not have to pay royalties to Gilead until the WHO declares an end to the COVID‑19 emergency or another medicine or

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In September 2022, the WHO updated their guidelines to recommend use of remdesivir for both non-hospitalized and hospitalized patients. This was based on final results from the SOLIDARITY trial that showed a reduction in mortality or progression to mechanical ventilation for non-ventilated patients.

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with remdesivir, for the treatment of suspected or laboratory-confirmed COVID‑19 in hospitalized people two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). The data supporting the EUA for baricitinib combined

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million vials would be going to American patients. However, HHS did not explain why several states with some of the highest caseloads had been omitted from the first two distribution rounds, including California, Florida, and Pennsylvania. In May 2020, Gilead indicated they would increase the number

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In January 2022, the Canadian component of the WHO Solidarity Trial reported that in-hospital people with COVID‑19 treated with remdesivir had 17% lower relative risk of death (18.7% versus 22.6% death rates) and 47% reduced relative risk for needing oxygen and mechanical ventilation (8.0%

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On 22 October 2020, the FDA approved remdesivir and also revised the EUA to permit the use of remdesivir for treatment of suspected or laboratory confirmed COVID‑19 in hospitalized children weighing 3.5 kilograms (7.7 lb) to less than 40 kilograms (88 lb) or hospitalized children

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to allocate shipments of remdesivir vials to American hospitals through the end of September 2020, and in exchange, during that three-month timeframe (July, August, and September), American patients would be allocated over 90% of Gilead's projected remdesivir output of more than 500,000 treatment

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In the United States, remdesivir is indicated for the treatment of COVID‑19 in people 28 days of age and older and weighing at least 3 kilograms (6.6 lb) who are hospitalized; or not hospitalized and have mild-to-moderate COVID‑19, and are at high risk for progression to severe

1896:(ECMO). The data supporting the EUA for baricitinib combined with remdesivir are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), which was conducted by the National Institute of Allergy and Infectious Diseases (NIAID). The EUA was issued to Eli Lilly and Company. 1301:

study of remdesivir assessing antiviral activity against SARS-CoV-2 was performed. Cells were pre-treated with the different doses of remdesivir for 1 hour, and the virus (MOI of 0.05) was subsequently added to allow infection for 2 hours. The results found that remdesivir functioned well as an

1521:(Cofepris) had already twice denied the approval of remdesivir because, in that agency's view, the evidence does not suggest "sufficient efficacy". In March 2020, Cofepris authorized the drug for emergency cases, advising to give continuous surveillance of the integral health of the patient. 1474:

In July 2020, the European Union granted a conditional marketing authorization for remdesivir with an indication for the treatment of COVID‑19 in adults and adolescents (aged twelve years and older with body weight at least 40 kilograms ) with pneumonia requiring supplemental oxygen.

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Remdesivir is approved, or authorized for emergency use, to treat COVID‑19 in many countries. Remdesivir has been authorized for emergency use in India, Singapore, and approved for use in Japan, the European Union, the United States, and Australia for people with severe symptoms.

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In August 2020, the FDA broadened the Emergency Use Authorization (EUA) for remdesivir to include all hospitalized patients with suspected or laboratory-confirmed COVID‑19, irrespective of the severity of their disease. The Fact Sheet was updated to reflect the new guidance.

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In October 2020, Gilead and HHS announced that HHS was relinquishing control over remdesivir allocation because production of the drug had finally caught up with US domestic demand. AmerisourceBergen will remain the sole distributor of Veklury in the US through the end of 2020.

3971: 1314:. The original end-to-end manufacturing process required 9 to 12 months to go from raw materials at contract manufacturers to finished product, but after restarting production in January 2020, Gilead Sciences was able to find ways to reduce the production time to six months. 1933:

or feline infectious peritonitis but has been available since 2019, through websites and social media as an unregulated black market substance. Because GS-441524 is the main circulating metabolite of remdesivir and because GS-441524 has similar potency against SARS-Cov-2

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approved requests to treat twelve people with remdesivir under the department's special-access program (SAP). Additional doses of remdesivir are not available through the SAP except for pregnant women or children with confirmed COVID‑19 and severe illness.

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In July 2020, remdesivir was provisionally approved for use in Australia for use in adults and adolescents with severe COVID‑19 symptoms who have been hospitalized. Australia claims to have a sufficient supply of remdesivir in its national stockpile.

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Infusion-related reactions. Infusion-related reactions have been seen during a remdesivir infusion or around the time remdesivir was given. Signs and symptoms of infusion-related reactions may include: low blood pressure, nausea, vomiting, sweating, and

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InChI=1S/C27H35N6O8P/c1-4-18(5-2)13-38-26(36)17(3)32-42(37,41-19-9-7-6-8-10-19)39-14-21-23(34)24(35)27(15-28,40-21)22-12-11-20-25(29)30-16-31-33(20)22/h6-12,16-18,21,23-24,34-35H,4-5,13-14H2,1-3H3,(H,32,37)(H2,29,30,31)/t17-,21+,23+,24+,27-,42-/m0/s1

6798: 3705:, Chun BK, Clarke MO, Doerffler E, Hui HC, Jordan R, Mackman RL, Parrish JP, Ray AS, Siegel D, "Methods for treating Filoviridae virus infections", published 5 May 2016, issued 8 August 2017, assigned to Gilead Sciences Inc. 1586:, then would allow each department to redistribute vials to hospitals in their respective states based upon each department's insight into "community-level needs." HHS also clarified that only 607,000 vials of Gilead's promised donation of 1.5 1577:

The initial distribution of the drug in the US was tripped up by seemingly capricious decision-making and finger-pointing, resulting in over a week of confusion and frustration among healthcare providers and patients alike. On 9 May 2020, the

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in 2022, for remdesivir treatment of children under age twelve who are COVID‑positive and not hospitalized, but have mild-to-moderate COVID‑19 with high risk of developing severe infection, including hospitalization or death.

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with remdesivir are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), which was conducted by the National Institute of Allergy and Infectious Diseases (NIAID). The EUA was issued to Eli Lilly and Company.

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in dichloromethane at −20 °C (−4 °F). The excess of boron trichloride was quenched in a mixture of potassium carbonate and methanol. A benzyl-free intermediate was obtained. The isomers were then separated via reversed-phase

6559:, Clarke MO, Feng JY, Jordan R, Mackman RL, Ray AS, Siegel D, "Methods for treating arenaviridae and coronaviridae virus infections", published 16 March 2017, issued 9 April 2019, assigned to Gilead Sciences, Inc. 5621: 5654: 6179: 1591:

of doses donated to the US from 607,000 to around 940,000. Some of the initial distribution was sent to the wrong hospitals, to hospitals with no intensive care units, and to facilities without the needed refrigeration to store it.

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for treating hospitalized adults who have a laboratory-confirmed SARS-CoV-2 infection with evidence of lung involvement, including a need for supplemental oxygen, abnormal chest X-rays, or illness requiring mechanical ventilation.

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requiring supplemental oxygen or those aged four weeks of age and older with body weight at least 40 kilograms (88 lb) who do not require supplemental oxygen and who are at high risk of progressing to severe COVID‑19.

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Increases in levels of liver enzymes, seen in abnormal liver blood tests. Increases in levels of liver enzymes have been seen in people who have received remdesivir, which may be a sign of inflammation or damage to cells in the

4158: 3670: 4938: 3724:, Clarke MO, Jordan R, Mackman RL, Ray AS, Siegel D, "Preparation of amino acid-containing nucleosides for treating flaviviridae virus infections", published 26 October 2017, assigned to Glead Sciences Inc 1908:

for hospitalized adults who have a laboratory-confirmed SARS-CoV-2 infection with evidence of lung involvement, including a need for supplemental oxygen, abnormal chest X-rays, or illness requiring mechanical ventilation.

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to start filling vials. The Edmonton plant finished its first new batch of remdesivir in April 2020. Around the same time, fresh raw materials began to arrive from contract manufacturers reactivated by Gilead in January.

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less than twelve years of age weighing at least 3.5 kilograms (7.7 lb). This decision was criticized for an alleged lack of previous consultation on part of the FDA given the complications of antiviral drug issues.

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that cause partial resistance to remdesivir were identified in 2018. These mutations make the viruses less effective in nature, and the researchers believe they will likely not persist where the drug is not being used.

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million vials for emergency use and estimated, as of April 2020, they had enough remdesivir for 140,000 treatment courses and expect to have 500,000 courses by October 2020, and one million courses by the end of 2020.

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In November 2020, the World Health Organization (WHO) updated its guideline on therapeutics for COVID‑19 to include a conditional recommendation against the use of remdesivir, triggered by results from the WHO

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In January 2022, a study indicated that nonhospitalized people who were at high risk for COVID‑19 progression had an 87% lower risk of hospitalization or death after a 3-day course of intravenous remdesivir.

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with remdesivir, for the treatment of suspected or laboratory confirmed COVID‑19 in hospitalized people two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or

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Gilead is transitioning the provision of emergency access to remdesivir from individual compassionate use via Health Canada's Special Access Program requests to access through clinical trials.

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In June 2020, Health Canada received an application from Gilead for the use of remdesivir for treating COVID‑19. On 27 July 2020, Health Canada conditionally approved the application.

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announced that Canada had entered into a deal to obtain up to 150,000 vials of remdesivir from Gilead starting in October. As of 8 October, remdesivir was still not widely available in

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vaccine is approved for COVID‑19, whichever comes first. On 23 June 2020, India granted emergency marketing approval of generic remdesivir manufactured by two Gilead licensees,

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Remdesivir requires "70 raw materials, reagents, and catalysts" to make, and approximately "25 chemical steps." Some of the ingredients are extremely dangerous to humans, especially

291: 6775: 6276: 5721:"Gilead's Investigational Antiviral Veklury (Remdesivir) Receives U.S. Food and Drug Administration Emergency Use Authorization for the Treatment of Patients With Moderate COVID-19" 4437: 1490:; Iran is planning to increase the productions of Remdesivir ampoules from 20,000 to 150,000 ampoules per month. It has also the permission of the "Food and Drug Administration" of 4968: 3890: 1164:

with remdesivir may reduce the antiviral activity of remdesivir. Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on

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In August 2020, the NIAID started the Adaptive COVID‑19 Treatment Trial 3 (ACTT 3) to evaluate the safety and efficacy of a treatment regimen consisting of remdesivir plus

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that started in 2018, along with further clinical trials, until August 2019, when Congolese health officials announced that it was significantly less effective than

1457:(EU/3/16/1615) was granted by the European Commission to Gilead Sciences International Ltd, United Kingdom, for remdesivir for the treatment of Ebola virus disease. 4875: 4052: 1191:

derivatives. The figure to the right is one of the synthesis routes of remdesivir invented by Chun and coauthors from Gilead Sciences. In this method, intermediate

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Preclinical and clinical research and development was done in collaboration between Gilead Sciences and various US government agencies and academic institutions.

1876:(NIAID) started the Adaptive COVID‑19 Treatment Trial 2 (ACTT-2) to evaluate the safety and efficacy of a treatment regimen consisting of remdesivir plus 6701: 5983: 1517:

stated at a news conference that Mexico would not necessarily follow the United States in approving the drug for use in Mexico. López-Gatell explained that the

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requiring supplemental oxygen and for adults who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID‑19.

6114: 3235:"Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency" 6137: 5455: 5302: 6591: 5205: 4661: 2161: 5182: 4586: 4464: 851:

for the treatment of COVID‑19 in adults and adolescents (aged twelve years and older with body weight at least 40 kilograms (88 lb)) with

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of 2013–2016, eventually being used in people with the disease. Preliminary results were promising; it was used in the emergency setting during the

178: 5677:"COVID-19 Update: FDA Broadens Emergency Use Authorization for Veklury (remdesivir) to Include All Hospitalized Patients for Treatment of COVID-19" 4802: 2712: 2088: 5078: 4555: 3948: 1756: 1468: 2764: 2383:

Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

7423: 127: 4991: 4396: 8095: 5481: 1843:'s COVID‑19 Clinical Pharmacology Task Group recommended that remdesivir only be administered to hospitalized patients as part of a 694: 6765: 6265: 4427: 7564: 4960: 3880: 1763:(USPTO). The USPTO granted two patents on remdesivir to Gilead Sciences on 9 April 2019: one for filoviruses, and one which covered both 1415: 1168:

data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.

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Another challenge is getting remdesivir into patients despite the drug's "poor predicted solubility and poor stability." In June 2020,

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World Health Organization (2017). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78".

7126:"Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis" 4252: 2223: 1760: 3439:"The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus" 7303: 2055: 1491: 874:

In Australia, it is approved for those aged four weeks of age and older with a body weight at least 3 kilograms (6.6 lb) with

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pregnant women), for reasons related to supply, citing the need to continue to provide the agent for testing in clinical trials.

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In March 2020, the drug was provisionally approved for use for COVID‑19 patients in a serious condition as a result of

1057:, it causes the RNA-dependent RNA polymerases to pause, but its predominant effect (as in Ebola) is to induce an irreversible 8085: 7980: 7072: 4780: 4356: 3364: 1791:(CDC). As a result of this work, it was recommended that remdesivir "should be further developed as a potential treatment." 1654:

for US private health insurance companies. The expected course of treatment is six vials over five days for a total cost of

6536: 5541: 3701: 6508:"Investigational compound remdesivir, developed by UAB and NIH researchers, being used for treatment of novel coronavirus" 5151: 1025:

in plasma, with GS-441524 being the major metabolite in plasma, and the only metabolite remaining two hours after dosing.

7625: 4432: 4042: 3081:"Frequently Asked Questions on the Emergency Use Authorization for Remdesivir for Certain Hospitalized COVID-19 Patients" 1893: 1566: 868: 7207: 6368: 4183: 3132:"Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19" 1969: 1302:

inhibitor of the infection. The study was published as a letter to the editor, and as such did not undergo peer review.

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was added and reacts for one additional hour, and the mixture was quenched in an aqueous sodium hydrogen carbonate. A

195: 8070: 7610: 6693: 3847:"FORMULATION FORUM – Application of Captisol Technology to Enable the Formulation of Remdesivir in Treating COVID-19" 1811: 1795: 1686: 714: 95: 1709:(RSV). It did not work against hepatitis C or RSV, but was then repurposed and studied as a potential treatment for 7997: 4992:"The FDA is allowing two drugs to be used for 'compassionate use' to treat the coronavirus. Here's what that means" 4221: 4074: 3808: 2060: 1963: 5411: 5269: 4289: 39: 5340: 4524: 4216: 358: 276: 159: 6618:"Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence" 6106: 8105: 5445: 1840: 1514: 3016:"Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial" 2586:"U.S. Food and Drug Administration Approves Gilead's Antiviral Veklury (remdesivir) for Treatment of COVID-19" 7281: 6976:"NIH Clinical Trial Testing Antiviral Remdesivir Plus Anti-Inflammatory Drug Baricitinib for COVID-19 Begins" 6830:"Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial" 6580: 6270: 4653: 2281:"Veklury 100 mg powder for concentrate for solution for infusion – Summary of Product Characteristics (SmPC)" 1918: 745: 6238: 5949:

Cohen J (27 October 2020). "The 'very, very bad look' of remdesivir, the first FDA-approved COVID-19 drug".

3747:"Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro" 2151: 7296: 5987: 5911: 5858: 5682: 5551: 5174: 4360: 4298: 4258: 4154: 4111: 3666: 3087: 2948: 2895: 2852: 2812: 1926: 1885: 1828: 1627: 1558: 1487: 1383: 1042: 936: 832: 603: 484: 4845: 1938:, some researchers have argued for the direct administration of GS-441524 as a COVID‑19 treatment. 1129:

concentrations of remdesivir are expected to decrease if it is administered together with cytochrome P450

553: 3721: 3286:"Synthesis and antiviral activity of a series of 1'-substituted 4-aza-7,9-dideazaadenosine C-nucleosides" 2622: 2027:"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)" 1889: 1844: 1706: 1634: 1562: 1054: 1014: 900: 564: 7268: 6877:

Agarwal A, Rochwerg B, Lamontagne F, Siemieniuk RA, Agoritsas T, Askie L, et al. (September 2020).

4428:"Australia has enough coronavirus drug remdesivir thanks to early supply donation, Health Minister says" 4151:"Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment" 3972:"Cipla, Hetero receive drug controller's emergency approval for Remdesivir for severe Covid-19 patients" 1505:

approved the drug for use in Japan, in a fast-tracked process, based on the US emergency authorization.

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law firm prosecuted various patent applications for remdesivir on behalf of Gilead Sciences before the

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Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, et al. (April 2019).

5237:"Gilead's experimental drug remdesivir shows 'hopeful' signs in small group of coronavirus patients" 8090: 8075: 7600: 920: 765: 7252: 5579:"Gilead donates Covid-19 drug remdesivir to Australia's medical stockpile after US buys up supply" 2251:"Veklury 100 mg concentrate for solution for infusion – Summary of Product Characteristics (SmPC)" 7985: 7737: 7289: 6723:

Lamontagne F, Agoritsas T, Macdonald H, Leo YS, Diaz J, Agarwal A, et al. (September 2020).

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Lo MK, Jordan R, Arvey A, Sudhamsu J, Shrivastava-Ranjan P, Hotard AL, et al. (March 2017).

4909:"Increasing the production of Remedisivir anti-corona drug by the executive staff of Farman Imam" 4733:"EMA recommends expanding remdesivir compassionate use to patients not on mechanical ventilation" 3636: 2431:

Scavone C, Brusco S, Bertini M, Sportiello L, Rafaniello C, Zoccoli A, et al. (April 2020).

1464:(EMA) provided recommendations on compassionate use of remdesivir for COVID‑19 in the EU. 1426: 1256: 1224: 232: 109: 5780:"Gilead Sciences Update on Supply and Distribution of Veklury (remdesivir) in the United States" 2318:"Veklury- remdesivir injection Veklury- remdesivir injection, powder, lyophilized, for solution" 8120: 7849: 7834: 7620: 7615: 5379:"Trump administration announces plan to distribute Covid-19 drug amid concerns over allocation" 5341:"Administration initially dispensed scarce covid-19 drug to some hospitals that didn't need it" 3813: 1722: 1334: 1317:

In January 2020, Gilead began working on restarting remdesivir production in glass-lined steel

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Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. (June 2017).

2399:"Gilead Announces Approval of Veklury (remdesivir) in Japan for Patients With Severe COVID-19" 1352:

On 12 May 2020, Gilead announced that it had granted non-exclusive voluntary licenses to five

473: 8115: 7796: 7791: 7741: 7605: 7022:"NIH Clinical Trial Testing Remdesivir Plus Interferon Beta-1a for COVID-19 Treatment Begins" 5984:"FDA Takes Actions to Expand Use of Treatment for Outpatients with Mild-to-Moderate COVID-19" 3545:

Chiotos K, Hayes M, Kimberlin DW, Jones SB, James SH, Pinninti SG, et al. (April 2020).

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In June 2020, HHS announced an unusual agreement with Gilead in which HHS agreed to Gilead's

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dropwise. After quenching the reaction in a weakly acidic aqueous solution, a mixture of 1:1

1232: 1094: 862:

In November 2020, the FDA issued an emergency use authorization (EUA) for the combination of

848: 780: 408: 6443:"U.S. government contributed research to a Gilead remdesivir patent – but didn't get credit" 5720: 2398: 2362: 8110: 7595: 6395: 6316: 5001: 4499:"Canadian experts don't see Remdesivir as a COVID-19 killer: 'This is not a silver bullet'" 3233:

Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, et al. (May 2020).

3130:

Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S, et al. (May 2020).

2667: 1430: 1342: 1326: 1070: 928: 493: 6555: 6303:"Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys" 4619:[Measures of the Ministry of Health of the Czech Republic – LP Remdesivir permit] 4397:"Remdesivir approved by the Therapeutic Goods Administration for severe coronavirus cases" 2945:"Coronavirus (COVID-19) Update: FDA Authorizes Drug Combination for Treatment of COVID-19" 2656:"Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys" 2215: 1478:

In August 2022, the European Union granted a full marketing authorization for remdesivir.

607: 584: 8: 5345: 5241: 3547:"Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2" 2892:"Coronavirus (COVID-19) Update: FDA Approves First COVID-19 Treatment for Young Children" 1803: 1799: 1710: 1583: 940: 888: 821: 802: 399: 239: 7248: 6399: 6320: 2671: 7786: 7691: 7273: 7150: 7125: 6952: 6927: 6926:

Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. (January 2022).

6908: 6854: 6829: 6642: 6617: 6418: 6383: 6337: 6302: 6230: 6082: 6057: 5962: 5450: 5274: 5146: 5055: 5028: 4008: 3976: 3771: 3746: 3573: 3546: 3527: 3514: 3489: 3465: 3438: 3414: 3387: 3310: 3285: 3261: 3234: 3205: 3180: 3156: 3131: 3040: 3015: 2728: 2688: 2655: 2627: 2559: 2546: 2524: 2467: 2454: 2432: 1930: 1922: 1905: 1827:

Remdesivir was approved for medical use in the United States in October 2020. The U.S.

1659: 1208: 1181: 1161: 206: 6384:"GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses" 6301:

Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. (March 2016).

6073: 5027:

Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. (June 2020).

3490:"Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment" 3031: 2654:

Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. (March 2016).

2280: 2258: 1650:

per vial for the governments of developed countries, including the United States, and

433: 8100: 7947: 7155: 6957: 6912: 6900: 6859: 6746: 6647: 6423: 6342: 6087: 5966: 5060: 3912: 3776: 3578: 3531: 3519: 3470: 3419: 3356: 3315: 3266: 3210: 3161: 3045: 2732: 2693: 2564: 2472: 1718: 1599: 1546: 1281: 1280:

mixture of remdesivir. In the end, optically pure remdesivir can be obtained through

1264: 1154: 1058: 1038: 1010: 761: 749: 315: 303: 151: 6828:

Ali K, Azher T, Baqi M, Binnie A, Borgia S, Carrier FM, et al. (January 2022).

3181:"Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses" 1996: 1223:; pyrrolo triazin-4-amine is brominated, and the amine group is protected by excess 7806: 7145: 7137: 6947: 6939: 6890: 6849: 6841: 6736: 6673: 6637: 6629: 6413: 6403: 6332: 6324: 6307: 6210: 6077: 6069: 5954: 5546: 5050: 5040: 4996: 4556:"Cases could spike sharply if Canadian epidemic stays on current course, Tam warns" 3766: 3758: 3568: 3558: 3509: 3505: 3501: 3460: 3450: 3409: 3399: 3388:"Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir" 3346: 3305: 3297: 3256: 3246: 3200: 3192: 3151: 3143: 3035: 3027: 2720: 2683: 2675: 2554: 2536: 2462: 2444: 1836: 1337:

revealed that Gilead has been managing those issues by mixing Ligand's proprietary

1318: 1212: 932: 912: 783:

infections before being studied as a post-infection treatment for COVID‑19.

620: 259: 57: 7094: 7064: 4772: 1403:

As of 11 April 2020, access in Canada was available only through clinical trials.

1235:

reaction with the bromide at −78 °C (−108 °F) to yield the intermediate

943:

reactions, including low blood pressure, nausea, vomiting, sweating or shivering.

137: 8054: 8030: 7327: 7323: 6581:

Antiviral Compound Provides Full Protection from Ebola Virus in Nonhuman Primates

6234: 6030: 5307: 4803:"NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19" 3917: 3720: 3334: 3196: 2713:"WHO launches global megatrial of the four most promising coronavirus treatments" 2402: 1730: 1698: 1598:, HHS would continue to work together with state governments and drug wholesaler 1582:(HHS) explained in a statement that it would be distributing remdesivir vials to 1382:

Remdesivir is the first treatment for COVID‑19 to be approved by the U.S.

1204: 1110: 1053:(ExoN), causing a decrease in viral RNA production. In some viruses, such as the 1050: 896: 753: 8049: 6633: 3284:

Cho A, Saunders OL, Butler T, Zhang L, Xu J, Vela JE, et al. (April 2012).

8042: 7991: 7931: 7510: 7315: 6447: 5478:"Trump Administration Secures New Supplies of Remdesivir for the United States" 5416: 5383: 3885: 3301: 3147: 2769: 2541: 1784: 1263:

intermediate was obtained. The protective group, benzyl, was then removed with

1228: 1002: 806: 7311: 6138:"Gilead Sciences agrees to sell to Europe up to 500,000 courses of remdesivir" 5113:"Gilead suspends emergency access to experimental coronavirus drug remdesivir" 4694:"EMA provides recommendations on compassionate use of remdesivir for COVID-19" 3762: 8064: 7524: 7180:. Feline Infectious Peritonitis Therapeutics/Clinical Trials Team, UC Davis. 7141: 7051: 7005: 6010: 5936: 5883: 5839: 5707: 4829: 4759: 4680: 4383: 4326: 4191: 4134: 3689: 3455: 3251: 3110: 2971: 2918: 2875: 2835: 2618: 2550: 2458: 2188: 2156: 1958: 1721:, this new line of research was carried out under the direction of scientist 1714: 1404: 1200: 1142: 1138: 1097: 1018: 813: 596: 386:)- triazin-7-yl)-5-cyano-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]phenoxy-( 328: 5958: 5749:"All Remdesivir Supplies to Be Distributed in U.S. by Maker Gilead Sciences" 5645:"UK emergency remdesivir supplies adequate to treat COVID-19, official says" 4104: 3632: 3563: 3080: 2805: 2765:"Gilead should ditch remdesivir and focus on its simpler and safer ancestor" 2724: 2490: 812:

The most common side effect in healthy volunteers is raised blood levels of

7906: 7901: 7871: 7845: 7830: 7820: 7657: 7579: 7477: 7428: 7398: 7319: 7159: 6961: 6928:"Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients" 6904: 6863: 6799:"Ad-hoc COVID-19 Clinical Pharmacology Task Group: Statement on remdesivir" 6770: 6750: 6668:(2021). Therapeutics and COVID-19: living guideline, 6 July 2021 (Report). 6651: 6427: 6346: 6172:"EU makes one billion-euro bet on Gilead's COVID drug before trial results" 6091: 5583: 5513: 5175:"U.S. emergency approval broadens use of Gilead's COVID-19 drug remdesivir" 5142:"U.S. Emergency Approval Broadens Use of Gilead's COVID-19 Drug Remdesivir" 5064: 3780: 3582: 3523: 3474: 3423: 3360: 3319: 3270: 3214: 3165: 3049: 2697: 2568: 2476: 1542: 1362: 1353: 1346: 1277: 1126: 924: 798: 254: 22: 6943: 5045: 1646:

In June 2020, Gilead announced that it had set the price of remdesivir at

1176: 7952: 7926: 7921: 7881: 7876: 7840: 7825: 7815: 7760: 7746: 7728: 7666: 7647: 7639: 7497: 7452: 7447: 7393: 7388: 7383: 7378: 7358: 7336: 4963:[Cofepris Issues Authorization For Emergency Use Of Remdesivir]. 2525:"Pharmacotherapy in COVID-19; A narrative review for emergency providers" 1877: 1780: 1779:(USAMRIID) announced preclinical results that remdesivir had blocked the 1746: 1742: 1702: 1619: 1454: 1418: 998: 904: 863: 825: 772: 757: 145: 6845: 6678: 6328: 6215: 5303:"Scoop: Trump officials' dysfunction harms delivery of coronavirus drug" 2679: 1851:

versus 15.0%) compared to people receiving standard-of-care treatments.

969: 453: 7962: 7957: 7778: 7723: 7718: 7713: 7709: 7701: 7671: 7574: 7569: 7559: 7554: 7534: 7519: 7492: 7482: 7472: 7462: 7418: 7413: 7408: 7403: 7373: 7368: 7363: 6027:"An Open Letter from Daniel O'Day, Chairman & CEO, Gilead Sciences" 4004:"India approves emergency use of remdesivir to treat Covid-19 patients" 3745:

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. (March 2020).

1764: 1134: 1074: 1022: 887:

The most common adverse effects in people treated with remdesivir were

656: 464: 6895: 6878: 6741: 6724: 6408: 5853:"FDA's approval of Veklury (remdesivir) for the treatment of COVID-19" 3881:"Gilead signs deals for generic companies to make and sell remdesivir" 3404: 3351: 2449: 7916: 7886: 7756: 7751: 7696: 7682: 7539: 7529: 7467: 7345: 7312: 4043:"Singapore approves remdesivir drug for emergency COVID-19 treatment" 1807: 1738: 1513:

In October 2020, Deputy Secretary of Prevention and Health Promotion

1338: 1276:

are reacted with trimethyl phosphate and methylimidazole to obtain a

1150: 1146: 1078: 1034: 986: 892: 875: 852: 795: 791: 419: 131: 6588:

United States Army Medical Research Institute of Infectious Diseases

4525:"Health Canada authorizes drug remdesivir for severe COVID-19 cases" 3437:

Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Götte M (April 2020).

3014:

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. (May 2020).

1777:

United States Army Medical Research Institute of Infectious Diseases

985:

of nucleotide) able to diffuse into cells, where it is converted to

7457: 6876: 5029:"Compassionate Use of Remdesivir for Patients with Severe Covid-19" 4075:"Japanese regulator approves Gilead's remdesivir to treat Covid-19" 2522: 2119:"COVID-19 treatment: Gilead Sciences Pty Ltd, remdesivir (Veklury)" 1322: 1297: 990: 916: 764:, remdesivir was approved or authorized for emergency use to treat 513: 444: 190: 5612:"Germany has for now enough remdesivir for COVID-19 therapy: govt" 4961:"Cofepris emite autorización para uso de emergencia de Remdesivir" 679: 7911: 7549: 7544: 7269:"How Remdesivir, New Hope for Covid-19 Patients, Was Resurrected" 7050: