2.1 Dosage and Administration Overview

• VEKLURY may only be administered in settings in which healthcare providers have immediate access to medications to treat a severe infusion or hypersensitivity reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary [see Dosage and Administration (2.5, 2.6), Warnings and Precautions (5.1)].
• Administer VEKLURY for the treatment of COVID-19 in adults and pediatric patients (birth to less than 18 years of age weighing at least 1.5 kg) by intravenous infusion only. Do not administer by any other route.
• There are TWO different formulations of VEKLURY:
  • VEKLURY for injection (supplied as 100 mg lyophilized powder in vial) must be reconstituted with Sterile Water for Injection prior to diluting with 0.9% sodium chloride injection.
    • The only approved dosage form of VEKLURY for pediatric patients weighing 1.5 kg to less than 40 kg is VEKLURY for injection (supplied as 100 mg lyophilized powder in vial).
  • VEKLURY injection (supplied as 100 mg/20 mL [5 mg/mL] solution in vial) must be further diluted in 250 mL of 0.9% sodium chloride injection infusion bag.
• There are differences in the way the two formulations are prepared. Carefully follow the product-specific preparation instructions below [see Dosage and Administration (2.5, 2.6)].

2.2 Testing Before Starting and During Treatment with VEKLURY

Perform hepatic laboratory testing in all patients before starting VEKLURY and while receiving VEKLURY as clinically appropriate [see Warnings and Precautions (5.2) and Use in Specific Populations (8.7)].

Determine prothrombin time in all patients before starting VEKLURY and monitor while receiving VEKLURY as clinically appropriate [see Adverse Reactions (6.1)].

2.3 Recommended Dosage in Adults and Pediatric Patients (Birth to Less than 18 Years of Age Weighing at Least 1.5 kg)

• The recommended dosage for adults and pediatric patients weighing at least 40 kg is a single loading dose of VEKLURY 200 mg on Day 1 via intravenous infusion followed by once-daily maintenance doses of VEKLURY 100 mg from Day 2 via intravenous infusion.
• The recommended dosage for pediatric patients weighing 1.5 kg to less than 40 kg is presented in Table 1.

The treatment course of VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19 has been made.

• The recommended total treatment duration for hospitalized patients requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) is 10 days.
• The recommended treatment duration for hospitalized patients not requiring invasive mechanical ventilation and/or ECMO is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days for a total treatment duration of up to 10 days.

2.4 Renal Impairment

No dosage adjustment of VEKLURY is recommended in patients with any degree of renal impairment, including patients on dialysis. VEKLURY may be administered without regard to the timing of dialysis [see Dosage and Administration (2.3) and Use in Specific Populations (8.4, 8.6)].

2.5 Dosage Preparation and Administration in Adults and Pediatric Patients Weighing at Least 40 kg

There are differences in the way the two formulations are prepared. Carefully follow the product-specific preparation instructions below.

2.6 Dosage Preparation and Administration in Pediatric Patients (Birth to Less than 18 Years of Age) Weighing 1.5 kg to Less than 40 kg

The only approved dosage form of VEKLURY for pediatric patients weighing 1.5 kg to less than 40 kg is VEKLURY for injection (supplied as 100 mg lyophilized powder in vial). Carefully follow the product-specific preparation instructions below.

Use VEKLURY for Injection (Supplied as 100 mg Lyophilized Powder in Vial) only.

2.7 Storage of Prepared Dosages

5.1 Hypersensitivity Including Infusion-related and Anaphylactic Reactions

Hypersensitivity reactions, including infusion-related and anaphylactic reactions, have been observed during and following administration of VEKLURY; most occurred within one hour. Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially prevent these signs and symptoms. Monitor patients during infusion and observe patients for at least one hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue administration of VEKLURY and initiate appropriate treatment. The use of VEKLURY is contraindicated in patients with known hypersensitivity to VEKLURY or any components of the product [see Contraindications (4)].

5.2 Increased Risk of Transaminase Elevations

Transaminase elevations have been observed in healthy volunteers who received 200 mg of VEKLURY followed by 100 mg doses for up to 10 days; the transaminase elevations were mild (Grade 1) to moderate (Grade 2) in severity and resolved upon discontinuation of VEKLURY. Transaminase elevations have also been reported in patients with COVID-19 who received VEKLURY [see Adverse Reactions (6.1)]. Because transaminase elevations have been reported as a clinical feature of COVID-19, and the incidence was similar in patients receiving placebo versus VEKLURY in clinical trials of VEKLURY, discerning the contribution of VEKLURY to transaminase elevations in patients with COVID-19 can be challenging.

Perform hepatic laboratory testing in all patients before starting VEKLURY and while receiving VEKLURY as clinically appropriate [see Dosage and Administration (2.1) and Use in Specific Populations (8.7)].

• Consider discontinuing VEKLURY if ALT levels increase to greater than 10 times the upper limit of normal.
• Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.

5.3 Risk of Reduced Antiviral Activity When Coadministered with Chloroquine Phosphate or Hydroxychloroquine Sulfate

Coadministration of VEKLURY and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments demonstrating a potential antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of VEKLURY [see Drug Interactions (7) and Microbiology (12.4)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness of VEKLURY for the treatment of COVID-19 have been established in pediatric patients from birth to less than 18 years of age and weighing at least 1.5 kg, who are:

• Hospitalized, or
• Not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

Use in this age group is supported by the following:

• Trials in adults [see Clinical Studies (14.1, 14.2, 14.3, 14.4, 14.5)]
• An open-label trial (Study 5823) in 58 hospitalized pediatric subjects [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.6)].

Use of VEKLURY in pediatric patients from birth to less than 18 years of age and weighing at least 1.5 kg is supported by Study 5823 where 58 hospitalized pediatric subjects were treated with weight-based VEKLURY for up to 10 days in the following cohorts:

• Cohorts 1–4, 8; infants, children, and adolescents: Subjects ≥12 years and weighing ≥40 kg (n=12); subjects <12 years and weighing ≥40 kg (n=5); subjects ≥28 days and weighing ≥20 to <40 kg (n=12); subjects ≥28 days and weighing ≥12 to <20 kg (n=12); and subjects ≥28 days and weighing ≥3 to <12 kg (n=12);
• Cohorts 5–7; neonates and infants: Subjects 14 to <28 days old, GA >37 weeks, and weighing ≥2.5 kg (n=3); subjects <14 days old, GA >37 weeks, and weighing ≥2.5 kg at birth (n=1); and subjects <56 days old, GA ≤37 weeks, and weighing ≥1.5 kg at birth (n=1).

The safety and pharmacokinetic results in pediatric subjects were similar to those in adults [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.6)].

Use of VEKLURY in pediatric patients weighing at least 40 kg is further supported by a clinical trial of VEKLURY in non-hospitalized subjects that included 3 pediatric subjects 12 years and older, and by clinical trials in hospitalized subjects that included 30 adult subjects weighing 40 to 50 kg. The safety in this weight group was comparable to adult subjects weighing greater than 50 kg. Thirty-nine pediatric patients 12 years and older and weighing at least 40 kg received VEKLURY in a compassionate use program in hospitalized subjects; the available clinical data from these patients are limited [see Adverse Reactions (6.1) and Clinical Studies (14)].

Use of VEKLURY in pediatric patients with renal impairment is supported by safety data in adults [see Adverse Reactions (6.1), Use in Specific Populations (8.6)]. Limited data are available regarding the safety of VEKLURY in pediatric patients with mild or moderate renal impairment. No data are available regarding the safety of VEKLURY in pediatric patients with severe renal impairment. In adults with severe renal impairment, including those requiring dialysis, exposures of GS-441524 and GS-704277, the metabolites of remdesivir, and betadex sulfobutyl ether sodium (SBECD) are increased [see Clinical Pharmacology (12.3)]. VEKLURY contains SBECD which, when administered intravenously, is eliminated through glomerular filtration and therefore when administered to pediatric patients with renal immaturity or renal impairment, may result in higher exposure to SBECD.

The safety and effectiveness of VEKLURY have not been established in pediatric patients weighing less than 1.5 kg.

8.5 Geriatric Use

Of the 1,062 hospitalized subjects with SARS-CoV-2 infection randomized in ACTT-1, 36% were 65 years or older. Of the 397 hospitalized subjects with SARS-CoV-2 infection randomized in Study GS-US-540-5773, 42% were 65 years or older. Of the 584 hospitalized subjects with SARS-CoV-2 infection randomized in Study GS-US-540-5774, 27% were 65 years or older. Of the 562 non-hospitalized subjects with SARS-CoV-2 infection randomized in Study GS-US-540-9012, 17% were 65 years or older. Reported clinical experience has not identified differences in responses between the elderly and younger patients [see Clinical Studies (14)]. No dosage adjustment is required in patients over the age of 65 years. In general, appropriate caution should be exercised in the administration of VEKLURY and monitoring of elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Renal Impairment

Use of VEKLURY in patients with COVID-19 and renal impairment, including those on dialysis, is supported by safety and pharmacokinetic data from the following:

• a randomized, double-blind, placebo-controlled trial (Study 5912) in adults [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].
• an open-label, parallel-group, single-dose trial in subjects with normal renal function and renal impairment (Study 9015) [see Clinical Pharmacology (12.3)].

The pharmacokinetics and safety of VEKLURY in patients with COVID-19 and renal impairment, including those on dialysis, were evaluated in 163 subjects in a randomized, double-blind, placebo-controlled trial, Study GS-US-540-5912 [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].

Study GS-US-540-5912 evaluated VEKLURY 200 mg once daily for 1 day followed by VEKLURY 100 mg once daily for 4 days (for a total of up to 5 days of intravenously administered therapy) in 243 hospitalized adult subjects with confirmed COVID-19 and renal impairment. The trial included 90 subjects (37%) with AKI (defined as a 50% increase in serum creatinine within a 48-hour period that was sustained for ≥6 hours despite supportive care), 64 subjects (26%) with CKD (eGFR <30 mL/minute/1.73m2), and 89 subjects (37%) with ESRD (eGFR <15 mL/minute/1.73m2) requiring hemodialysis. Subjects were randomized in a 2:1 manner, stratified by ESRD, high-flow oxygen requirement, and region (US vs ex-US) to receive VEKLURY (n=163) or placebo (n=80), plus standard of care.

At baseline, mean age was 69 years (with 62% of subjects aged 65 or older); 57% of subjects were male, 67% were White, 26% were Black, and 3% were Asian. The most common baseline risk factors were hypertension (89%), diabetes mellitus (79%), and cardiovascular or cerebrovascular disease (51%); the distribution of risk factors was similar between the two treatment groups. A total of 45 subjects (19%) were on high-flow oxygen, 144 (59%) were on low-flow oxygen, and 54 (22%) were on room air at baseline; no subjects were on invasive mechanical ventilation (IMV). A total of 182 subjects (75%) were not on renal replacement therapy, and 31 subjects (13%) had received a COVID-19 vaccine.

The safety results in subjects with COVID-19 and renal impairment, including those on dialysis, were consistent with those observed in clinical trials of VEKLURY in adults [see Adverse Reactions (6.1)]. Study GS-US-540-5912 closed prematurely due to feasibility issues and was underpowered to assess for efficacy because of lower than expected enrollment.

The pharmacokinetics and safety of VEKLURY in subjects with normal renal function and renal impairment, including those on dialysis, were evaluated in 75 subjects (43 subjects with renal impairment plus 32 matched control subjects with normal renal function) in an open-label, parallel-group, single-dose trial, Study GS-US-540-9015 [see Clinical Pharmacology (12.3)].

In studies GS-US-540-5912 and GS-US-540-9015, exposures of GS-441524 and GS-704277, the metabolites of remdesivir, and SBECD are increased in subjects with mild to severe renal impairment, including those requiring dialysis, relative to subjects with normal renal function [see Clinical Pharmacology (12.3)].

No dosage adjustment of VEKLURY is recommended for patients with any degree of renal impairment, including those on dialysis [see Dosage and Administration (2.2, 2.4), Use in Specific Populations (8.4)].

8.7 Hepatic Impairment

No dosage adjustment of VEKLURY is recommended for patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C) [see Clinical Pharmacology (12.3)].

Perform hepatic laboratory testing in all patients before starting VEKLURY and while receiving VEKLURY as clinically appropriate [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)].

12.1 Mechanism of Action

Remdesivir is an antiviral drug with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [see Microbiology (12.4)].

12.2 Pharmacodynamics

Remdesivir and metabolites exposure-response relationships and the time course of pharmacodynamics response are unknown.

12.3 Pharmacokinetics

The pharmacokinetic (PK) properties of remdesivir and metabolites are provided in Table 14. The multiple dose PK parameters of remdesivir and metabolites in adults with COVID-19 are provided in Table 15.

12.4 Microbiology

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

Intravenous administration (slow bolus) of remdesivir to male rhesus monkeys at dosage levels of 5, 10, and 20 mg/kg/day for 7 days resulted, at all dose levels, in increased mean urea nitrogen and increased mean creatinine, renal tubular atrophy, and basophilia and casts.

Intravenous administration (slow bolus) of remdesivir to rats at dosage levels of ≥3 mg/kg/day for up to 4 weeks resulted in findings indicative of kidney injury and/or dysfunction.

Kidney-related effects in rats and monkeys were observed at exposures of the predominant circulating metabolite (GS-441524) that are lower than the exposure in humans at the RHD.

14.1 Description of Clinical Trials

The efficacy and safety of VEKLURY were evaluated in the trials summarized in Table 22.

14.2 NIAID ACTT-1 Study in Hospitalized Subjects with Mild/Moderate and Severe COVID-19

A randomized, double-blind, placebo-controlled clinical trial (ACTT-1) of hospitalized adult subjects with confirmed SARS-CoV-2 infection and mild, moderate, or severe COVID-19 compared treatment with VEKLURY for 10 days (n=541) with placebo (n=521). Mild/moderate disease was defined as SpO2 >94% and respiratory rate <24 breaths/minute without supplemental oxygen; severe disease was defined as an SpO2 ≤94% on room air, a respiratory rate ≥24 breaths/minute, an oxygen requirement, or a requirement for mechanical ventilation. Subjects had to have at least one of the following to be enrolled in the trial: radiographic infiltrates by imaging, SpO2 ≤94% on room air, a requirement for supplemental oxygen, or a requirement for mechanical ventilation. Subjects treated with VEKLURY received 200 mg on Day 1 and 100 mg once daily on subsequent days, for 10 days of treatment via intravenous infusion. Treatment with VEKLURY was stopped in subjects who were discharged from the hospital prior to the completion of 10 days of treatment.

At baseline, mean age was 59 years (with 36% of subjects aged 65 or older); 64% of subjects were male, 53% were White, 21% were Black, and 13% were Asian; 24% were Hispanic or Latino; 105 subjects had mild/moderate disease (10% in both treatment groups); 957 subjects had severe disease (90% in both treatment groups). Subjects in this trial were unvaccinated. A total of 285 subjects (27%) (n=131 received VEKLURY) were on invasive mechanical ventilation or ECMO. The most common comorbidities were hypertension (51%), obesity (45%), and type 2 diabetes mellitus (31%); the distribution of comorbidities was similar between the two treatment groups.

The primary clinical endpoint was time to recovery within 29 days after randomization. Recovery was defined as discharged from the hospital without limitations on activities, discharged from the hospital with limitations on activities and/or requiring home oxygen, or hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care. The median time to recovery was 10 days in the VEKLURY group compared to 15 days in the placebo group (recovery rate ratio 1.29 [95% CI 1.12 to 1.49], p<0.001). Among subjects with mild/moderate disease at enrollment (n=105), the median time to recovery was 5 days in both the VEKLURY and placebo groups (recovery rate ratio 1.22 [95% CI 0.82 to 1.81]). Among subjects with severe disease at enrollment (n=957), the median time to recovery was 11 days in the VEKLURY group compared to 18 days in the placebo group (recovery rate ratio 1.31 [95% CI 1.12 to 1.52]).

A key secondary endpoint was clinical status on Day 15 assessed on an 8-point ordinal scale consisting of the following categories:

1. not hospitalized, no limitations on activities;
2. not hospitalized, limitation on activities and/or requiring home oxygen;
3. hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
4. hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
5. hospitalized, requiring supplemental oxygen;
6. hospitalized, on noninvasive ventilation or high-flow oxygen devices;
7. hospitalized, on invasive mechanical ventilation or ECMO; and
8. death.

Overall, the odds of improvement in the ordinal scale were higher in the VEKLURY group at Day 15 when compared to the placebo group (odds ratio 1.54 [95% CI 1.25 to 1.91]).

Overall, 29-day mortality was 11% for the VEKLURY group vs 15% for the placebo group (hazard ratio 0.73 [95% CI 0.52 to 1.03]).

14.3 Study GS-US-540-5773 in Hospitalized Subjects with Severe COVID-19

A randomized, open-label multi-center clinical trial (Study 5773) in adult subjects with confirmed SARS-CoV-2 infection, an SpO2 of ≤94% on room air, and radiological evidence of pneumonia compared 200 subjects who received VEKLURY for 5 days with 197 subjects who received VEKLURY for 10 days. Treatment with VEKLURY was stopped in subjects who were discharged from the hospital prior to completion of their protocol-defined duration of treatment. Subjects on mechanical ventilation at screening were excluded. All subjects received 200 mg of VEKLURY on Day 1 and 100 mg once daily on subsequent days via intravenous infusion, plus standard of care.

At baseline, the median age of subjects was 61 years (range, 20 to 98 years); 64% were male, 75% were White, 12% were Black, and 12% were Asian; 22% were Hispanic or Latino. More subjects in the 10-day group than the 5-day group required invasive mechanical ventilation or ECMO (5% vs 2%), or high-flow oxygen support (30% vs 25%), at baseline. Subjects in this trial were unvaccinated. Median duration of symptoms and hospitalization prior to first dose of VEKLURY were similar across treatment groups.

The primary endpoint was clinical status on Day 14 assessed on a 7-point ordinal scale consisting of the following categories:

1. death;
2. hospitalized, receiving invasive mechanical ventilation or ECMO;
3. hospitalized, receiving noninvasive ventilation or high-flow oxygen devices;
4. hospitalized, requiring low-flow supplemental oxygen;
5. hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to COVID-19);
6. hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol for remdesivir administration); and
7. not hospitalized.

Overall, after adjusting for between-group differences at baseline, subjects receiving a 5-day course of VEKLURY had similar clinical status at Day 14 as those receiving a 10-day course (odds ratio for improvement 0.75 [95% CI 0.51 to 1.12]). There were no statistically significant differences in recovery rates or mortality rates in the 5-day and 10-day groups once adjusted for between-group differences at baseline. All-cause mortality at Day 28 was 12% vs 14% in the 5- and 10-day treatment groups, respectively.

14.4 Study GS-US-540-5774 in Hospitalized Subjects with Moderate COVID-19

A randomized, open-label multi-center clinical trial (Study 5774) of hospitalized adult subjects with confirmed SARS-CoV-2 infection, SpO2 >94% and radiological evidence of pneumonia compared treatment with VEKLURY for 5 days (n=191) and treatment with VEKLURY for 10 days (n=193) with standard of care (n=200). Treatment with VEKLURY was stopped in subjects who were discharged from the hospital prior to completion of their protocol-defined duration of treatment. Subjects treated with VEKLURY received 200 mg on Day 1 and 100 mg once daily on subsequent days via intravenous infusion.

At baseline, the median age of subjects was 57 years (range, 12 to 95 years); 61% were male, 61% were White, 19% were Black, and 19% were Asian; 18% were Hispanic or Latino. Subjects in this trial were unvaccinated. Baseline clinical status, oxygen support status, and median duration of symptoms and hospitalization prior to first dose of VEKLURY were similar across treatment groups.

The primary endpoint was clinical status on Day 11 assessed on a 7-point ordinal scale consisting of the following categories:

1. death;
2. hospitalized, receiving invasive mechanical ventilation or ECMO;
3. hospitalized, receiving noninvasive ventilation or high-flow oxygen devices;
4. hospitalized, requiring low-flow supplemental oxygen;
5. hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to COVID-19);
6. hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol for remdesivir administration); and
7. not hospitalized.

Overall, the odds of improvement in the ordinal scale were higher in the 5-day VEKLURY group at Day 11 when compared to those receiving only standard of care (odds ratio 1.65 [95% CI 1.09 to 2.48], p=0.017). The odds of improvement in clinical status with the 10-day treatment group when compared to those receiving only standard of care were not statistically significant (odds ratio 1.31 [95% CI 0.88 to 1.95]). All-cause mortality at Day 28 was ≤2% in all treatment groups.

14.5 Study GS-US-540-9012 in Non-Hospitalized Subjects with Mild-to-Moderate COVID-19 and at High Risk for Progression to Severe Disease

A randomized, double-blind, placebo-controlled, clinical trial (Study 9012) evaluated VEKLURY 200 mg once daily for 1 day followed by VEKLURY 100 mg once daily for 2 days (for a total of 3 days of intravenously administered therapy) in 554 adult and 8 pediatric subjects (12 years of age and older and weighing at least 40 kg) who were non-hospitalized, had mild-to-moderate COVID-19, were symptomatic for COVID-19 for ≤7 days, had confirmed SARS-CoV-2 infection, and had at least one risk factor for progression to hospitalization. Risk factors for progression to hospitalization included age ≥60 years, obesity (BMI ≥30), chronic lung disease, hypertension, cardiovascular or cerebrovascular disease, diabetes mellitus, immunocompromised state, chronic mild or moderate kidney disease, chronic liver disease, current cancer, and sickle cell disease. Subjects who received, required, or were expected to require supplemental oxygen were excluded from the trial. Subjects were randomized in a 1:1 manner, stratified by residence in a skilled nursing facility (yes/no), age (<60 vs ≥60 years), and region (US vs ex-US) to receive VEKLURY (n=279) or placebo (n=283), plus standard of care.

At baseline, mean age was 50 years (with 30% of subjects aged 60 or older); 52% were male, 80% were White, 8% were Black, and 2% were Asian; 44% were Hispanic or Latino; median body mass index was 30.7 kg/m2. Subjects in this trial were unvaccinated. VEKLURY or placebo was first administered to subjects in outpatient facilities (84%), home healthcare settings (13%), or skilled nursing facilities (3%). The most common comorbidities were diabetes mellitus (62%), obesity (56%), and hypertension (48%). Median (Q1, Q3) duration of symptoms prior to treatment was 5 (3, 6) days; median viral load was 6.3 log10 copies/mL at baseline. The baseline demographics and disease characteristics were well balanced across the VEKLURY and placebo treatment groups.

The primary endpoint was the proportion of subjects with COVID-19 related hospitalization (defined as at least 24 hours of acute care) or all-cause mortality through Day 28. Events occurred in 2 (0.7%) subjects treated with VEKLURY compared to 15 (5.3%) subjects concurrently randomized to placebo (hazard ratio 0.134 [95% CI 0.031 to 0.586]; p=0.0076). No deaths were observed through Day 28.

14.6 Study GS-US-540-5823 in Hospitalized Pediatric Subjects with COVID-19

The primary objectives of this Phase 2/3 single-arm, open-label clinical trial (Study GS-US-540-5823) were to evaluate pharmacokinetics and safety of up to 10 days of treatment with VEKLURY in pediatric subjects. A total of 58 pediatric subjects from birth (including preterm to term infants) to <18 years of age and weighing at least 1.5 kg with confirmed SARS-CoV-2 infection and mild, moderate, or severe COVID-19 was evaluated in eight cohorts:

• Cohorts 1–4, 8; infants, children, and adolescents: Subjects ≥12 years and weighing ≥40 kg (n=12); subjects <12 years and weighing ≥40 kg (n=5); subjects ≥28 days and weighing ≥20 to <40 kg (n=12); subjects ≥28 days and weighing ≥12 to <20 kg (n=12); and subjects ≥28 days and weighing ≥3 to <12 kg (n=12). Subjects weighing ≥40 kg received 200 mg of VEKLURY on Day 1 followed by VEKLURY 100 mg once daily on subsequent days; subjects weighing ≥3 kg to <40 kg received VEKLURY 5 mg/kg on Day 1 followed by VEKLURY 2.5 mg/kg once daily on subsequent days;
• Cohorts 5–7; neonates and infants: Subjects 14 to <28 days old, GA >37 weeks, and weighing ≥2.5 kg (n=3); subjects <14 days old, GA >37 weeks, and weighing ≥2.5 kg at birth (n=1); and subjects <56 days old, GA ≤37 weeks, and weighing ≥1.5 kg at birth (n=1). Subjects 14 to <28 days old, GA >37 weeks, and weighing ≥2.5 kg received VEKLURY 5 mg/kg on Day 1 followed by VEKLURY 2.5 mg/kg once daily on subsequent days. Subjects <14 days old, GA >37 weeks, and weighing at least 2.5 kg at birth, and subjects <56 days old, GA ≤37 weeks, and weighing ≥1.5 kg at birth, received VEKLURY 2.5 mg/kg on Day 1 followed by VEKLURY 1.25 mg/kg once daily on subsequent days.

Assessments occurred at the following intervals: Screening; Day 1 (Baseline); Days 2–10, or until discharge, whichever came earlier; Follow-Up on Day 30 (±5). Treatment with VEKLURY was stopped in subjects who were discharged from the hospital prior to the completion of 10 days of treatment.

How Supplied

Storage and Handling

Do not reuse or save reconstituted or diluted VEKLURY for future use. These products contain no preservative; therefore, partially used vials should be discarded [see Dosage and Administration (2.5)].

Hypersensitivity Reactions

Inform patients that hypersensitivity reactions have been seen in patients receiving VEKLURY during and after infusion. Advise patients to inform their healthcare provider if they experience any of the following: changes in heart rate; fever; shortness of breath, wheezing; swelling of the lips, face, or throat; rash; nausea; sweating; or shivering [see Warnings and Precautions (5.1)].

Increased Risk of Transaminase Elevations

Inform patients that VEKLURY may increase the risk of hepatic laboratory abnormalities. Advise patients to alert their healthcare provider immediately if they experience any symptoms of liver inflammation [see Warnings and Precaution (5.2)].

Drug Interactions

Inform patients that VEKLURY may interact with other drugs. Advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including chloroquine phosphate or hydroxychloroquine sulfate [see Warnings and Precautions (5.3), Drug Interactions (7), and Microbiology (12.4)].

Pregnancy Registry

Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in individuals exposed to VEKLURY during pregnancy [see Use in Specific Populations (8.1)].

Pregnancy

Inform patients to notify their healthcare provider in the event of a pregnancy [see Use in Specific Populations (8.1)].