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Veklury (Remdesivir) Antiviral

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December 13, 2023
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Veklury (Remdesivir) Antiviral

Gilead Sciences, Inc. Veklury® (remdesivir; GS-5734, DESREM, Redyx) is a nucleotide analog with broad-spectrum antiviral activity. Gilead Sciences Veklury inhibits the SARS-CoV-2 RNA-dependent RNA polymerase, which is essential for viral replication. Veklury is a prodrug that distributes into cells and is metabolized into the pharmacologically active remdesivir triphosphate (RDV-TP). RDV-TP acts as an analog of ATP and competes with it to incorporate nascent viral RNA. It incorporates RDV-TP into developing viral delayingly chain termination (position i+3) and disrupting SARS-CoV-2 viral RNA replication.

The Company developed remdesivir to treat hepatitis C and was subsequently investigated for Ebola and Marburg viruses. In addition, Gilead announced on Oct. 22, 2020, that the U.S. Food and Drug Administration (FDA) approved Veklury for use in adult and pediatric patients 12 years of age and older and weighing at least 40 kilograms (about 88 pounds) for treatment of COVID-19 requiring hospitalization. On Mar. 7, 2021, the European Medicines Agency (EMA) issued marketing approval in the E.U. 

The World Health Organization (WHO) issued a conditional recommendation in 2020 against the use of remdesivir in hospitalized patients, regardless of disease severity. On April 22, 2022, following the publication of new data from a clinical trial looking at the outcome of hospital admission, the WHO suggested using remdesivir in mild or moderate COVID-19 patients at high risk of hospitalization.

On May 2, 2022, a WHO-funded phase 3 clinical study published by The Lancet concluded that Remdesivir had no significant effect on patients with COVID-19 who are already being ventilated. However, among other hospitalized patients, it has a negligible impact on death or progression to ventilation.

Gilead announced positive data on Feb. 21, 2023, from three retrospective real-world studies demonstrating that initiation of Veklury® (remdesivir) within the first two days of hospital admission can help reduce mortality and hospital readmission rates among all patients hospitalized with COVID-19 regardless of disease severity. On Apr. 16, 2023, Gilead announced a Phase 3 Clinical Trial Demonstrated Veklury's Safety Profile in Patients with Severe Renal Impairment, and Real-World Evidence Demonstrated Veklury Reduced COVID-19- Associated Mortality and Readmission Rates in Immunocompromised Patients Across All Variants of Concern, Including Omicron.

On July 14, 2023, the Company announced that Veklury is the first approved antiviral COVID-19 treatment that can be used across all stages of renal disease. Based on in vitro analyses presented at CROI, Veklury retains potent antiviral activity against recent Omicron subvariants of concern, including XBB, BQ 1.1, BA.2.75, BA.4, BA 4.6, and BA.5. The journal Clinical Infectious Diseases published a study on August 9, 2023, which concluded prompt initiation of remdesivir in immunocompromised patients hospitalized for COVID-19 is associated with significant survival benefits across all variant waves. 

Gilead Sciences announced on Aug. 24, 2023, the FDA approved a sNDA for the use of Veklury® with no dose adjustments to treat COVID-19 in people with mild, moderate, and severe hepatic impairment. This approval follows the recent FDA and European Commission decisions to extend the approved use of Veklury to treat COVID-19 in people with severe renal impairment, including those on dialysis.

ChemSpider ID: 58827832; ChEMBL Id: 4065616; Accession Number: DB14761 Formula: C27H35N6O8P; Molar mass: 602.585 g/mol; PubChem CID: 121304016. They updated fact sheets for healthcare providers and parents/caregivers and FAQs. Billing codes for the U.S. are located at this CMS link.

Gilead Science, Inc. (Nasdaq: GILD) is in Foster City, CA, 94404.

Veklury Availability

Veklury is approved in more than 50 countries worldwide.

Veklury History

Veklury was the first antiviral treatment for COVID-19 to receive FDA approval. In 2009, Remdesivir research programs were underway in hepatitis C and respiratory syncytial virus. In the fall of 2015, Gilead Sciences applied for two patents for remdesivir, one for combating coronaviruses, including SARS and MERS. Gilead Science first received a patent (US9724360B2) for the drug (remdesivir) to treat Ebola in 2017.

Veklury Side Effects

The U.S. FDA says 'possible side effects include increased levels of liver enzymes, which may be a sign of liver injury; and allergic reactions, which may include changes in blood pressure and heart rate, low blood oxygen level, even addition, due shortness of breath, wheezing, swelling (e.g., lips, around eyes, under the skin), rash, nausea, sweating or shivering.'

Veklury is contraindicated in patients with a history of clinically significant hypersensitivity reactions to Veklury or its components. Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and after Veklury's administration. The most common adverse reaction (≥5% of all grades) was nausea. The most common lab abnormalities (≥5% of all grades) were increases in ALT and AST. Drug interaction trials of Veklury and other concomitant medications have not been conducted in humans. Drug interaction trials of Veklury and other concomitant medications have not been shown in humans, confirms the U.S. FDA. This article, published in Mar. 2023, provides a brief overview of redeliver-induced bradycardia, diagnosis, and treatment.

Veklury Children

A 3-day course of IV remdesivir initiated within seven days of symptom onset is the second preferred treatment option after Paxlovid for adults and pediatric patients, says the U.S. CDC.

Remdesivir Generic

India-based Zydus announced on March 24, 2021, that its version of Remdesivir, Remdac, is more affordable at Rs. 899 for a 100 mg lyophilized injection. Remdac was launched in Aug. 2020 at Rs. 2800.

Obeldesivir (GS-5245)

Gilead is also working to advance an investigational oral nucleoside prodrug, obeldesivir, that, when metabolized, forms the same active metabolite as remdesivir. BIRCH is a Phase 3, global, randomized, double-blind, placebo-controlled study that will compare the efficacy and safety of obeldesivir with placebo in non-hospitalized participants at high risk for developing severe COVID-19. 

Veklury News

September 22, 2023 - A study - Remdesivir Is Associated With Reduced Mortality in COVID-19 Patients Requiring Supplemental Oxygen Including Invasive Mechanical Ventilation Across SARS-CoV-2 Variants - Concluded: Remdesivir treatment is associated with significantly reduced mortality among patients hospitalized for COVID-19 requiring supplemental oxygen upon admission, including those requiring HFO/NIV or IMV/ECMO with severe or critical disease, across VOC periods.

July 14, 2023 - Meghan Sise, MD, Department of Nephrology at Massachusetts General Hospital, said in a press release, "This latest update to the prescribing information for remdesivir now includes patients with advanced CKD and ESKD."

April 16, 2023 - "The breadth of clinical and real-world evidence data presented at ECCMID further support the strong efficacy and safety profile of Veklury," said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences.

March 19, 2023 - This retrospective analysis study is the first real-world evidence that RDV remains effective during the dominance of more pathogenic SARS-CoV-2 variants and those that cause a milder course of the disease and continue to be an essential element of COVID-19 therapy.

February 22, 2023 - Gilead is also working to advance an investigational oral nucleoside prodrug, GS-5245, that, when metabolized, forms the same active metabolite as remdesivir.

November 22, 2022 - Study: Real-world evidence of novel treatments for COVID-19 on mortality: a nationwide comparative cohort study of hospitalized patients in the Netherlands' the 1st, 2nd, 3rd, and 4thlands. Conclusions - Both remdesivir and corticosteroids were associated with better outcomes in ward patients with COVID-19.

September 15, 2022 - The WHO conditional recommendation for Veklury's use in the treatment of patients with severe COVID-19 is mainly driven by the final results of the WHO-sponsored SOLIDARITY study, which showed a statistically significant 17% lower relative risk of death or progression to needing ventilation in patients requiring supplemental oxygen at baseline, compared to standard of care (R.R.: 0.83; 95% CI: 0.75–0.93). 

August 16, 2022 - Gilead conducted in vitro analyses of Veklury activity against Omicron subvariants BA.2.12.1, BA.4, and BA.5, results continued to confirm that Veklury retains antiviral activity against all Omicron subvariants analyzed to date. 

July 19, 2022 - New Agreement Enables The Rapid and Equitable Access to Veklury for COVID-19 Patients in E.U. and EEA Countries.

June 15, 2022 - The U.S. CDC published Interim Clinical Considerations for COVID-19 Treatment in Outpatients.

May 2, 2022 - The peer-reviewed journal The Lancet published the final results of Solidarity and meta-analyses of mortality in all relevant t data. Interpretation: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalized patients, it has a negligible impact on death or progression to ventilation (or both).

May 2, 2022 - The Lancet published an Editorial: When and which patients should receive remdesivir?

April 25, 2022 - Patrizia Cavazzoni, M.D., director of the FDA's Center for Drug Evaluation and Research, stated in a press release, "Today's approval of the first COVID-19 therapeutic for this (pediatric) population demonstrates the agency's commitment to that need." This approval is supported by a phase 2/3, single-arm, open-label clinical study of 53 pediatric patients at least 28 days of age and weighing at least 3 kilograms (about 7 pounds) with confirmed SARS-CoV-2 infection and mild, moderate, or severe COVID-19. The safety and pharmacokinetic results from the phase 2/3 study in pediatric subjects were similar to those in adults.

April 21, 2022 - The Company announced an updated WHO guideline recognizes the important role of Veklury in helping people at high risk of COVID-19 disease progression but does not currently reflect the broad body of evidence supporting Veklury's effectiveness across a broad spectrum of disease severity, as do several other global treatment guidelines. We anticipate the WHO will continue to consider robust evidence from multiple randomized, controlled trials, including ACTT-1 and independent meta-analysis, which demonstrate the efficacy of Veklury in later-stage COVID-19 disease and update their recommendation for patients with a severe or critical illness. 

February 11, 2022 - Gilead released data from a non-peer-reviewed study demonstrating the in vitro activity of Veklury® (remdesivir) against ten SARS-CoV-2 variants, including Omicron. Previous study results confirmed Veklury's antiviral activity against Alpha, Beta, Gamma, Delta, and Omicron.

January 7, 2022 - The Centers for Medicare & Medicaid Services issued a new Healthcare Common Procedure Coding System code for VEKLURY (remdesivir) when administered in the outpatient setting: Long descriptor: Injection, remdesivir, 1 mg; Short descriptor: Inj, remdesivir, 1 mg.

November 2, 2021 - A phase 3 clinical trial found that a 3-day course of intravenous Veklury in outpatients at high risk of progression to severe COVID-19 significantly reduced the risk of hospitalization by 87% versus placebo.

October 26, 2021 - V.A. Study Questions Value of Remdesivir in Hospitalized COVID-19 Patients.

October 19, 2021 - Gilead announced that the Company would donate 100,000 vials of Veklury to help address the recent surge of COVID-19 cases in Indonesia and 3,000 vials to Armenia.

September 22, 2021 - Gilead Sciences, Inc., announced positive results from a Phase 3 randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of a three-day course of Veklury® (remdesivir) for intravenous use in treating COVID-19 in non-hospitalized patients at high risk for disease progression.

June 21, 2021 - Gilead Sciences, Inc. announced positive data from three retrospective studies of the real-world treatment of patients hospitalized with COVID-19, adding to the body of mortality and hospital discharge data for patients treated with Veklury® (remdesivir).

March 24, 2021 - The JAMA published a multicenter comparative effectiveness research study that included 2,483 consecutive admissions with a high proportion of non-White individuals. Treatment with remdesivir was associated with more rapid clinical improvement than no remdesivir receipt in the propensity score-matched controls. However, adding corticosteroids to remdesivir was not associated with improved time to death.

February 17, 2021 - A new study funded by the U.S. National Institutes of Health will evaluate the effects of remdesivir in pregnant women who have been prescribed the drug to treat COVID-19. The study, conducted at 17 sites in the continental USA and Puerto Rico, aims to determine how pregnant women metabolize the drug and any potential side effects.

February 12, 2021 - The European Medicines Agency (EMA) concluded, following a safety review, that remdesivir (Veklury) is not associated with acute kidney injury. Veklury received conditional marketing authorization from the EMA and is indicated for treating COVID-19 in adults and adolescents (12 years or older) with pneumonia requiring supplemental oxygen.

February 9, 2021 - The Annals of Internal Medicine published 'Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2).' Our current understanding of COVID-19 progression is that patients who are admitted on mechanical ventilation or ECMO have likely progressed beyond the viral stage of the illness to the inflammatory phase and are less likely to improve from antivirals; hence, it is essential to avoid any additional toxicity from remdesivir, unless there is evidence for potential benefit.

December 2, 2020 - An editorial published by the NEJM found that 'The approval of remdesivir (Veklury) marked an important step toward addressing the needs of patients with COVID-19. But, the absence of a demonstrated survival benefit highlights the need for continued therapeutic development.'

November 20, 2020 - The WHO announced a conditional recommendation age of remdesivir (Veklury) in hospitalized patients, regardless of disease severity.

November 19, 2020 - In a phase II study conducted in West Africa, last updated on September 30, 2020, Veklury (GS-5734) reduced Ebola viral matter in the semen of male survivors, according to Dehkontee Gayedyu-Dennis, MD, of the Partnership for Research on Vaccines and Infectious Diseases in Paynesville, Liberia, speaking at the virtual meeting of the American Society of Tropical Medicine & Hygiene.

November 5, 2020 - The NEJM published 'Remdesivir for the Treatment of Covid-19 — Final Report.' Our data show that remdesivir was superior to placebo in shortening recovery in adults hospitalized with COVID-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705)

August 21, 2020 - JAMA: Effect of Remdesivir vs. Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19. Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant clinical status difference from standard e at 11 days after treatment initiation. Patients randomized to a 5-day course of remdesivir had a statistically significant clinical status that differed from usual care, but the difference was uncertain clinical importance.

July 6, 2020 - Mylan N.V. announced that India's Drug Controller General had approved its remdesivir 100 mg/vial for restricted emergency use in India's COVID-19 patients. The drug is approved to treat suspected or laboratory-confirmed incidences of COVID-19 in adults and children hospitalized with severe disease presentations. The drug will be launched under the brand name DESREM™ in India.

June 29, 2020 - The U.S. Department of Health and Human Services announced an agreement with Gilead Sciences to secure ample supplies of the drug remdesivir for the United States through September. American hospitals can purchase the drug in amounts allocated to HHS and state health departments. HHS has secured 500,000 treatment courses for American hospitals through September 2020.

May 1, 2020 - The U.S. FDA issued an emergency use authorization for the investigational antiviral drug remdesivir to treat suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.

April 29, 2020 - Gilead Announces Results From Phase 3 Trial of Investigational Antiviral Remdesivir in Patients With Severe COVID-19. Preliminary results indicate that patients who received remdesivir had a 31% faster recovery time than placebo (p<0.001). Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received a placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059).

April 10, 2020 - Gilead Sciences announced results from a cohort analysis of 53 patients hospitalized with severe complications of COVID-19 who were treated with the investigational antiviral remdesivir on an individual compassionate use basis. Most patients in this international cohort demonstrated clinical improvement, and no new safety signals were identified with remdesivir treatment. The New England Journal of Medicine published the detailed results of this analysis today.

February 25, 2020 - A randomized, controlled clinical trial to evaluate the safety and efficacy of the investigational antiviral remdesivir in hospitalized adults diagnosed with COVID-19 began at the University of Nebraska Medical Center in Omaha.

Veklury Clinical Trials

Gilead has initiated various clinical studies to evaluate the safety and efficacy of remdesivir in adults diagnosed with COVID-19 following the U.S. FDA's rapid review and acceptance of Gilead's investigational new drug filing.

April 16, 2023 - Results from a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study (REDPINE) evaluated the safety of Veklury in patients with moderately and severely reduced kidney function who were hospitalized for COVID-19, a population with increased COVID-19-related mortality. The trial included 243 hospitalized adult participants with confirmed COVID-19 and renal impairment, including 90 participants (37%) with acute kidney injury (AKI), 64 participants (26%) with chronic kidney disease (CKD), and 89 participants (37%) with end-stage kidney disease (ESKD) requiring hemodialysis. Patients were randomized 2:1 to receive Veklury (n=163) or placebo (n=80) in addition to the standard of care. No new safety signals were observed in the study, and no other adverse reactions to Veklury were identified in 163 hospitalized patients with AKI (n=60), CKD (n=44), or ESKD (n=59) on hemodialysis receiving Veklury for up to 5 days.

The approval of Veklury for use in non-hospitalized patients on January 21, 2022, is supported by a randomized, placebo-controlled phase 3 clinical trial that included 562 non-hospitalized patients with mild-to-moderate COVID-19 who were at high risk for progression to severe COVID-19, including hospitalization or death.

On January 17, 2022, the results from the COVID-19: Canadian Arm of the phase 2 SOLIDARITY Trial (CATCO) - 3-arms in a 1:1:1 ratio randomization to either the control arm, consisting of standard supportive care treatment for COVID-19 or remdesivir plus standard supportive care or Interferon-beta-1a plus standard supportive care. Interpretation: Remdesivir, when compared with the standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation.

Study to Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) Treatment of Coronavirus Disease 2019 (COVID-19) in an Outpatient Setting: ClinicalTrials.gov Identifier: NCT04501952 The PINETREE was a Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of a three-day course of Veklury IV in reducing the rate of hospitalization or all-cause death among non-hospitalized COVID-19 patients at high risk for disease progression. 

On March 24, 2021, the Journal of Antimicrobial Chemotherapy reported a meta-analysis of five randomized clinical trials. Remdesivir treatment of hospitalized patients with noncritical COVID-19 was associated with better clinical improvement, shorter recovery, hospital stays, and safety.

A Phase 3 study, NCT04315948, is a multicenter, adaptive, randomized trial of the safety and efficacy of treatments for COVID-19 in hospitalized adults. Remdesivir will be administered as a 200 mg intravenous loading dose on Day 1 and a 100 mg once-daily intravenous maintenance dose for up to ten entire courses. Results were published on September 14, 2021.

Topline results from the open-label, Phase 3 SIMPLE trial reported that the time to clinical improvement for 50 percent of patients was ten days in the 5-day treatment group and 11 days in the 10-day treatment group. 

Clinical Trials