Veklury (Remdesivir) Antiviral Clinical Trials, Dosage, Indication, Side Effects
Gilead Sciences, Inc. Veklury® (remdesivir; GS-5734, DESREM, Redyx) is a nucleotide analog with broad-spectrum antiviral activity. Veklury inhibits the SARS-CoV-2 RNA-dependent RNA polymerase, 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 delaying 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. 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.
On April 26, 2024, Gilead announced Veklury sales decreased 3% to $555 million in the first quarter of 2024, compared to the same period in 2023.
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 Indication
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.
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.
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.
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.
