Remdesivir

[22] Remdesivir is a prodrug that is intended to allow intracellular delivery of GS-441524 monophosphate and subsequent biotransformation into GS-441524 triphosphate, a ribonucleotide analogue inhibitor of viral RNA polymerase.

[31] Other reported adverse effects include gastrointestinal distress, elevated transaminase levels in the blood (liver enzymes), infusion site reactions, and electrocardiogram abnormalities.

[42][24] Blood plasma concentrations of remdesivir are expected to decrease if it is administered together with cytochrome P450 inducers such as rifampicin, carbamazepine, phenobarbital, phenytoin, primidone, and St John's wort.

[48] In January 2020, Gilead began working on restarting remdesivir production in glass-lined steel chemical reactors at its manufacturing plant in Edmonton, Alberta.

[49] On 12 May 2020, Gilead announced that it had granted non-exclusive voluntary licenses to five generic drug companies in India and Pakistan to manufacture remdesivir for distribution to 127 countries.

[50][51][52] 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 vaccine is approved for COVID‑19, whichever comes first.

[19] Remdesivir has been authorized for emergency use in India,[54] Singapore,[55] and approved for use in Japan,[56] the European Union, the United States, and Australia for people with severe symptoms.

[68][7] In September 2020, Minister of Public Services and Procurement Anita Anand announced that Canada had entered into a deal to obtain up to 150,000 vials of remdesivir from Gilead starting in October.

[71] In February 2016, orphan designation (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.

[74] The updated recommendations were based on preliminary results from the NIAID-ACTT study,[75] which suggested a beneficial effect of remdesivir in the treatment of hospitalized individuals with severe COVID‑19.

[74] 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 [88 lb]) with pneumonia requiring supplemental oxygen.

López-Gatell explained that the Federal Commission for the Protection against Sanitary Risk (Cofepris) had already twice denied the approval of remdesivir because, in that agency's view, the evidence does not suggest "sufficient efficacy".

[55] In March 2020, United States President Donald Trump announced that remdesivir was available for "compassionate use" for people with COVID‑19; FDA Commissioner Stephen Hahn confirmed the statement at the same press conference.

[20][83] On 23 March 2020, Gilead voluntarily suspended access for compassionate use (excepting cases of critically ill children and pregnant women), for reasons related to supply, citing the need to continue to provide the agent for testing in clinical trials.

[84][85] In May 2020, the US Food and Drug Administration granted Gilead emergency use authorization (EUA) for remdesivir to be distributed and used by licensed healthcare providers to treat adults and children hospitalized with severe COVID‑19.

[88][89] 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.

[98] 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,[99] Germany,[100] and the United Kingdom.

[101] 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.

[27] 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).

[27] Remdesivir received approval from the US Food and Drug Administration (FDA) in October 2020, for use in adults and children twelve years and older requiring hospitalization for treatment of severe COVID‑19 infections.

[110] In June 2020, Gilead announced that it had set the price of remdesivir at US$390 per vial for the governments of developed countries, including the United States, and US$520 for US private health insurance companies.

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".

[120] A collaboration of researchers from the Centers for Disease Control and Prevention (CDC) and Gilead Sciences subsequently discovered that remdesivir had antiviral activity in vitro against multiple filoviruses, pneumoviruses, paramyxoviruses, and coronaviruses.

[126] In October 2015, the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) announced preclinical results that remdesivir had blocked the Ebola virus in Rhesus monkeys.

[127] The "initial screening" of the "Gilead Sciences compound library to find molecules with promising antiviral activity" was performed by scientists at the Centers for Disease Control and Prevention (CDC).

Preliminary results were promising; it was used in the emergency setting during the Kivu Ebola epidemic that started in 2018, along with further clinical trials, until August 2019, when Congolese health officials announced that it was significantly less effective than monoclonal antibody treatments such as ansuvimab and atoltivimab/maftivimab/odesivimab.

[61][62][63][108] The US Food and Drug Administration (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.

[108] 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 Solidarity trial.

[129][130][131][132] Meanwhile, the Public Health Agency of Canada's COVID‑19 Clinical Pharmacology Task Group recommended that remdesivir only be administered to hospitalized patients as part of a randomized controlled trial due to limited information on risks and benefits.