Remdesivir was originally created and developed by Gilead Sciences in 2009, as part of the company's research and development program for hepatitis C. It did not work against hepatitis C as hoped, but was then repurposed and studied as a potential treatment for Ebola virus disease and Marburg virus infections. According to the Czech News Agency, this new line of research was carried out under the direction of scientist Tomáš Cihlář. A collaboration of researchers from the CDC and Gilead Sciences subsequently discovered that remdesivir had antiviral activity in vitro against multiple filoviruses, pneumoviruses, paramyxoviruses, and coronaviruses.
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. 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 Centers for Disease Control and Prevention (CDC). As a result of this work, it was recommended that remdesivir "should be further developed as a potential treatment."
On 17 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.
Mutations in the mouse hepatitis virus RNA replicase 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.
Remdesivir was rapidly pushed through clinical trials due to the West African Ebola virus epidemic of 2013–2016, eventually being used in people with the disease. 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 mAb114 and REGN-EB3. The trials, however, established its safety profile.
GS-441524 was shown in 2019, to have promise for treating feline infectious peritonitis caused by a coronavirus. It has not been evaluated or approved by the US Food and Drug Administration (FDA) for the treatment of feline coronavirus or feline infectious peritonitis but has been available since 2019, through websites and social media as an unregulated black market substance as confirmed by the UC Davis School of Veterinary Medicine. Because GS-441524 is the main circulating metabolite of remdesivir and because GS-441524 has similar potency against SARS-Cov-2 in vitro, some researchers have argued for the direct administration of GS-441524 as a COVID19 treatment.
During the mid-2010s, the Mintz Levin law firm prosecuted various patent applications for remdesivir on behalf of Gilead Sciences before the United States Patent and Trademark Office (USPTO). The USPTO granted two patents on remdesivir to Gilead Sciences on 9 April 2019: one for filoviruses, and one which covered both arenaviruses and coronaviruses.
In January 2020, Gilead Sciences began laboratory testing of remdesivir against SARS-CoV-2, stating that remdesivir had been shown to be active against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) in animal models. On 21 January 2020, the Wuhan Institute of Virology applied for a Chinese "use patent" for treating COVID‑19.
In January 2020, Gilead began working on restarting remdesivir production in glass-lined steel chemical reactors at its manufacturing plant in Edmonton, Alberta. On 2 February 2020, the company flew its entire stock of remdesivir, 100 kilograms in powder form (left over from Ebola research), to its filling plant in La Verne, California 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.
In a trial in China over February–March 2020, remdesivir was not effective in reducing the time for improvement from COVID‑19 or deaths, and caused various adverse effects, requiring the investigators to terminate the trial.
On 17 March 2020, the drug was provisionally approved for use for COVID‑19 patients in a serious condition as a result of the outbreak in the Czech Republic.
On 18 March 2020, the World Health Organization (WHO) announced the launch of a trial that would include one group treated with remdesivir. Other clinical trials are underway or planned.
On 20 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. 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 pregnant women), for reasons related to supply, citing the need to continue to provide the agent for testing in clinical trials.
As of 11 April 2020, access in Canada was available only through clinical trials. Health Canada 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.
In April 2020, the European Medicines Agency (EMA) provided recommendations on compassionate use of remdesivir for COVID‑19 in the EU.
In April 2020, the European Medicines Agency (EMA) started a 'rolling review' of data on the use of remdesivir in COVID‑19. It completed the review in May 2020.
On 1 May 2020, the US Food and Drug Administration granted Gilead emergency use authorization (EUA) for remdesivir to be distributed and used by licensed health care 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 extracorporeal membrane oxygenation (ECMO), a heart–lung bypass machine. Distribution of remdesivir under the EUA will be controlled by the US government for use consistent with the terms and conditions of the EUA. Gilead will supply remdesivir to authorized distributors, or directly to a US government agency, who will distribute 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 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.
Preliminary data from an international multi-center, placebo controlled double-blind randomized trial carried out by the US National Institutes of Health suggests that remdesivir is effective in reducing the recovery time from 15 to 11 days in people hospitalized with COVID‑19. On 29 April 2020, based on results of the ACTT trial, the National Institute of Allergy and Infectious Diseases (NIAID) announced that remdesivir was better than a placebo in reducing time to recovery for people hospitalized with advanced COVID‑19 and lung involvement. The study appeared on The New England Journal of Medicine website almost a month later on 22 May 2020 and, despite generally positive results, the study concluded that "given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient." A previous Chinese study published in The Lancet did not show significant benefits or drawbacks of using remdesivir, concluding that further research is required to understand the effectiveness of the drug. John David Norrie of the Clinical Trials Unit of the University of Edinburgh Medical School criticised that article as underpowered due to a lack of significant results as well as the fact that the study was ended prematurely. Based on the results of its study, the NIH stopped the ACTT trial and provided remdesivir to participants assigned to received placebo.
As of April 2020 , remdesivir was viewed as the most promising treatment for COVID‑19, and was included among four treatments under evaluation in the international Solidarity trial and European Discovery trial. The FDA stated, on 1 May 2020, that it is "reasonable to believe" that known and potential benefits of remdesivir outweigh its known and potential risks in some specific populations hospitalized with severe COVID‑19.
In May 2020, the National Institute of Allergy and Infectious Diseases (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 baricitinib 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.
On 11 May 2020, the Committee for Medicinal Products for Human Use (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.
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. 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. On 23 June 2020, India granted emergency marketing approval of generic remdesivir manufactured by two Gilead licensees, Cipla and Hetero Drugs.
On 7 May 2020, Japan's Ministry of Health, Labour and Welfare approved the drug for use in Japan, in a fast-tracked process based on the US emergency authorization.
Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. Remdesivir is being tested as a treatment for COVID‑19, and has been authorized for emergency use in the US, India, Singapore, and approved for use in Japan, the European Union, and Australia for people with severe symptoms. It also received approval in the UK in May 2020; however, it was going to be rationed due to limited supply. It may shorten the time it takes to recover from the infection.
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 health care providers and patients alike. On 9 May 2020, the United States Department of Health and Human Services (HHS) explained in a statement that it would be distributing remdesivir vials to state health departments, 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 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 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.
Another challenge is getting remdesivir into patients despite the drug's "poor predicted solubility and poor stability." In June 2020, Ligand Pharmaceuticals revealed that Gilead has been managing those issues by mixing Ligand's proprietary excipient Captisol (based on University of Kansas research into cyclodextrin) 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.
In June 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) started evaluating remdesivir for a conditional marketing authorization after receiving an application from Gilead Sciences. On 25 June 2020, the committee recommended granting a conditional marketing authorization for remdesivir for the treatment of COVID‑19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen. The brand name will be Veklury.
On 15 June 2020, the FDA updated the fact sheets for the emergency use authorization of remdesivir to warn that using chloroquine or hydroxychloroquine with remdesivir may reduce the antiviral activity of remdesivir. Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.
On 19 June 2020, Health Canada received a new application to authorize remdesivir for treating COVID‑19.
On 29 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. The expected course of treatment is six vials over five days for a total cost of US$2,340. Being a repurposed drug, the minimum production cost for remdesivir is estimated at US$0.93 per day of treatment.
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.
On 3 July 2020, the European Union granted a conditional marketing authorization for remdesivir with an indication for the treatment of coronavirus disease 2019 (COVID‑19) in adults and adolescents (aged 12 years and older with body weight at least 40 kilograms [88 lb]) with pneumonia requiring supplemental oxygen. At the end of July, the European Union secured a €63 million (US$74 million) contract with Gilead, to make the drug available there in early August of 2020.
Remdesivir was approved for medical use in the European Union in July 2020. It is indicated for the treatment of coronavirus disease 2019 (COVID‑19) in adults and adolescents (aged 12 years and older with body weight at least 40 kg) with pneumonia requiring supplemental oxygen.
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 interferon beta-1a 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.
On 28 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.
On 29 June, HHS announced an unusual agreement with Gilead in which HHS agreed to Gilead's wholesale acquisition price, HHS would continue to work together with state governments and drug wholesaler AmerisourceBergen 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 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.