Veklury
Generic: REMDESIVIR
Basic Information
Manufacturer
Gilead Sciences, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
c0978fa8-53ff-4ca2-82a7-567fd3e958ca
Indications & Usage
1 INDICATIONS AND USAGE VEKLURY is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients (birth to less than 18 years of age weighing at least 1.5 kg) who are [see Clinical Studies (14) ] : 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.
VEKLURY is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleotide analog RNA polymerase inhibitor indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients (birth to less than 18 years of age 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.
( 1 )
VEKLURY is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleotide analog RNA polymerase inhibitor indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients (birth to less than 18 years of age 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.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Hypersensitivity Including Infusion-related and Anaphylactic Reactions [see Warnings and Precautions (5.1) ] Increased Risk of Transaminase Elevations [see Warnings and Precautions (5.2) ] The most common adverse reactions (incidence greater than or equal to 5%, all grades) observed with treatment with VEKLURY are nausea, ALT increased, and AST increased.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc.
at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
Clinical Trials in Adult Subjects The safety of VEKLURY is based on data from four Phase 3 studies in 1,476 hospitalized adult subjects with COVID-19, one Phase 3 study in 279 non-hospitalized adult and pediatric subjects (12 years of age and older weighing at least 40 kg) with mild-to-moderate COVID-19, four Phase 1 studies in 131 healthy adults, and from patients with COVID-19 who received VEKLURY under the Emergency Use Authorization or in a compassionate use program.
Clinical Trials Experience in Adults with COVID-19 NIAID ACTT-1 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized subjects with mild, moderate, and severe COVID-19 treated with VEKLURY (n=532) or placebo (n=516) for up to 10 days.
Subjects treated with VEKLURY received 200 mg on Day 1 and 100 mg once daily on subsequent days [see Clinical Studies (14.1) ] .
The collection of adverse event data in this trial was limited to severe (Grade 3) or potentially life-threatening (Grade 4) adverse events, serious adverse events, adverse events leading to study drug discontinuation, and moderate (Grade 2) severity or higher hypersensitivity reactions.
Rates of adverse reactions (≥ Grade 3), serious adverse reactions, and adverse reactions leading to treatment discontinuation are presented in Table 4.
Table 4 Summary of Adverse Reaction Rates in Hospitalized Subjects with Mild, Moderate, or Severe COVID-19 in NIAID ACTT-1 Types of Adverse Reactions VEKLURY N=532 n (%) Placebo N=516 n (%) Adverse reactions, Grades ≥3 41 (8%) 46 (9%) Serious adverse reactions 2 (0.4%) Seizure (n=1), infusion-related reaction (n=1).
3 (0.6%) Adverse reactions leading to treatment discontinuation 11 (2%) Seizure (n=1), infusion-related reaction (n=1), transaminases increased (n=3), ALT increased and AST increased (n=1), GFR decreased (n=2), acute kidney injury (n=3).
15 (3%) Study GS-US-540-5773 was a randomized, open-label clinical trial in hospitalized subjects with severe COVID-19 treated with VEKLURY 200 mg on Day 1 and 100 mg once daily for 5 (n=200) or 10 days (n=197).
Adverse reactions were reported in 33 (17%) subjects in the 5-day group and 40 (20%) subjects in the 10-day group [see Clinical Studies (14.2) ] .
The most common adverse reactions occurring in at least 5% of subjects in either the VEKLURY 5-day or 10-day group, respectively, were nausea (5% vs 3%), AST increased (3% vs 6%), and ALT increased (2% vs 7%).
Rates of any adverse reactions, serious adverse reactions, and adverse reactions leading to treatment discontinuation are presented in Table 5.
Table 5 Summary of Adverse Reaction Rates in Hospitalized Subjects with Severe COVID-19 in Study 5773 Types of Adverse Reactions VEKLURY 5 Days N=200 n (%) VEKLURY 10 Days N=197 n (%) Any adverse reaction, all Grades 33 (17%) 40 (20%) Serious adverse reactions 3 (2%) Transaminases increased (n=5), hepatic enzyme increased (n=1), hypertransaminasaemia (n=1).
4 (2%) Adverse reactions leading to treatment discontinuation 5 (3%) Transaminases increased (n=4), hepatic enzyme increased (n=2), LFT increased (n=2), hypertransaminasaemia (n=1), ALT increased (n=1), ALT increased and AST increased (n=2), injection site erythema (n=1), rash (n=1).
9 (5%) Study GS-US-540-5774 was a randomized, open-label clinical trial in hospitalized subjects with moderate COVID-19 treated with VEKLURY 200 mg on Day 1 and 100 mg daily for 5 (n=191) or 10 days (n=193), or standard of care (SOC) only (n=200) [see Clinical Studies (14.3) ] .
Adverse reactions were reported in 36 (19%) subjects in the 5-day group and 25 (13%) subjects in the 10-day group.
The most common adverse reaction occurring in at least 5% of subjects in the VEKLURY groups was nausea (7% in the 5-day group, 4% in the 10-day group).
Rates of any adverse reactions, serious adverse reactions, and adverse reactions leading to treatment discontinuation are presented in Table 6.
Table 6 Summary of Adverse Reaction Attribution of events to study drug was not performed for the SOC group.
Rates in Hospitalized Subjects with Moderate COVID-19 in Study 5774 Types of Adverse Reactions VEKLURY 5 Days N=191 n (%) VEKLURY 10 Days N=193 n (%) Any adverse reaction, all Grades 36 (19%) 25 (13%) Serious adverse reactions 1 (<1%) Heart rate decreased.
0 Adverse reactions leading to treatment discontinuation 4 (2%) ALT increased (n=2), ALT increased and AST increased (n=1), hypertransaminasaemia (n=1), blood alkaline phosphatase increased (n=1), rash (n=2), heart rate decreased (n=1).
4 (2%) Study GS-US-540-9012 was a randomized, double-blind, placebo-controlled clinical trial in subjects who were non-hospitalized, 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 treated with VEKLURY (n=279; 276 adults and 3 pediatric subjects 12 years of age and older weighing at least 40 kg) or placebo (n=283; 278 adults and 5 pediatric subjects 12 years of age and older weighing at least 40 kg) for 3 days.
Of the 279 subjects treated with VEKLURY, 227 subjects received at least one dose of VEKLURY at an outpatient facility, 44 subjects received at least one dose of VEKLURY in a home healthcare setting, and 8 subjects received at least one dose of VEKLURY at a skilled nursing facility.
Subjects treated with VEKLURY received 200 mg on Day 1 and 100 mg once daily on subsequent days [see Clinical Studies (14.4) ] .
Adverse reactions (all grades) were reported in 34 (12%) subjects in the VEKLURY group and 25 (9%) subjects in the placebo group.
The most common adverse reaction occurring in at least 5% of subjects in the VEKLURY group was nausea (6%).
There were no serious adverse reactions or adverse reactions leading to treatment discontinuation in either treatment group.
Safety in subjects who received VEKLURY in a home healthcare setting was comparable to that observed in the overall GS-US-540-9012 study population, but these findings are based on limited data.
Less Common Adverse Reactions in Adults from Clinical Trials Clinically significant adverse reactions that were reported in <2% of subjects exposed to VEKLURY in clinical trials are listed below: Hypersensitivity reactions [see Warnings and Precautions (5.1) ].
Generalized seizure Rash Laboratory Abnormalities Study GS-US-399-5505 was a Phase 1, randomized, blinded, placebo-controlled clinical trial in healthy volunteers administered VEKLURY 200 mg on Day 1 and 100 mg for either 4 days or 9 days.
Mild (Grade 1, n=8) to moderate (Grade 2, n=1) elevations in ALT were observed in 9 of 20 subjects receiving 10 days of VEKLURY; the elevations in ALT resolved upon discontinuation of VEKLURY.
No subjects (0 of 9) who received 5 days of VEKLURY had graded increases in ALT.
The frequencies of laboratory abnormalities (Grades 3–4) occurring in at least 3% of subjects with COVID-19 receiving VEKLURY in Trials NIAID ACTT-1, 5773, and 5774 are presented in Table 7, Table 8, and Table 9, respectively.
Table 7 Laboratory Abnormalities (Grades 3–4) Reported in ≥3% of Hospitalized Subjects with Mild, Moderate, or Severe COVID-19 in NIAID ACTT-1 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 10 Days N=532 Placebo N=516 ALT increased 3% 6% AST increased 6% 8% Bilirubin increased 2% 5% Creatinine clearance decreased Based on the Cockcroft-Gault formula.
18% 20% Creatinine increased 15% 16% eGFR decreased 18% 24% Glucose increased 12% 13% Hemoglobin decreased 15% 22% Lymphocytes decreased 11% 18% Prothrombin time increased 9% 4% Table 8 Laboratory Abnormalities (Grades 3–4) Reported in ≥3% of Hospitalized Subjects with Severe COVID-19 in Trial 5773 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 5 Days N=200 VEKLURY 10 Days N=197 ALT increased 6% 8% AST increased 7% 6% Creatinine clearance decreased Based on the Cockcroft-Gault formula.
10% 19% Creatinine increased 5% 15% Glucose increased 11% 8% Hemoglobin decreased 6% 8% Table 9 Laboratory Abnormalities (Grades 3–4) Reported in ≥3% of Hospitalized Subjects with Moderate COVID-19 in Trial 5774 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 5 Days N=191 VEKLURY 10 Days N=193 SOC N=200 SOC=Standard of care.
ALT increased 2% 3% 8% Creatinine clearance decreased Based on the Cockcroft-Gault formula.
2% 5% 8% Glucose increased 4% 3% 2% Hemoglobin decreased 3% 1% 6% The frequencies of laboratory abnormalities (Grades 3–4) occurring in at least 2% of subjects with COVID-19 receiving VEKLURY in Trial GS-US-540-9012 are presented in Table 10.
Table 10 Laboratory Abnormalities (Grades 3–4) Reported in ≥2% of Non-Hospitalized Subjects in Trial 9012 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 3 Days N=279 Placebo N=283 Creatinine clearance decreased Based on the Cockcroft-Gault formula.
6% 2% Creatinine increased 3% 1% Glucose increased 6% 6% Lymphocytes decreased 2% 1% Prothrombin time increased 1% 2% Clinical Trials Experience in Adults with COVID-19 and Renal Impairment Study GS-US-540-5912 was a randomized, double-blind, placebo-controlled clinical trial in which 163 hospitalized subjects with confirmed COVID-19 and acute kidney injury (AKI; N=60), chronic kidney disease (CKD; eGFR <30 mL/minute/1.73m 2 ; N=44), or end-stage renal disease (ESRD; eGFR <15 mL/minute/1.73m 2 ; N=59) on hemodialysis received VEKLURY for up to 5 days [see Use in Specific Populations (8.6) ].
The adverse reactions observed were consistent with those observed in clinical trials of VEKLURY in adults.
Adverse reactions (all grades) were reported in 13 (8%) subjects in the VEKLURY group and 3 (4%) subjects in the placebo group.
The most common adverse reactions were nausea (1%), abdominal pain (1%), and diarrhea (1%).
No subjects experienced serious adverse reactions.
One subject permanently discontinued treatment due to an adverse reaction: lipase increased.
The frequencies of laboratory abnormalities (Grades 3–4) occurring in at least 3% of subjects with COVID-19 receiving VEKLURY in Trial GS-US-540-5912 are presented in Table 11.
Table 11 Laboratory Abnormalities (Grades 3–4) Reported in ≥3% of Hospitalized Subjects in Trial 5912 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 5 Days N=163 Placebo N=80 Lymphocytes decreased 27% 27% Hemoglobin decreased 25% 25% Glucose increased 15% 19% Uric acid increased 11% 4% Creatinine increased 12% 14% Albumin decreased 12% 10% Lipase increased 12% 7% Prothrombin time increased 11% 4% Prothrombin INR increased 7% 4% AST increased 6% 4% Thromboplastin time increased 5% 4% ALT increased 5% 6% Sodium increased 3% 3% Calcium increased 3% 0 Clinical Trials in Pediatric Subjects Study GS-US-540-5823 was a Phase 2/3, single-arm, open-label clinical trial in hospitalized subjects from birth to <18 years of age and weighing at least 1.5 kg with mild, moderate, and severe COVID-19 treated with weight-based VEKLURY (n=58) for up to 10 days [see Clinical Studies (14.6) ] : Cohorts 1, 8: Subjects ≥12 years and weighing ≥40 kg (n=12) and subjects <12 years and weighing ≥40 kg (n=5): Received 200 mg on Day 1 and 100 mg once daily on subsequent days.
Cohorts 2–4: 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): Received 5 mg/kg on Day 1 and 2.5 mg/kg once daily on subsequent days.
Cohort 5: Subjects 14 to <28 days old, gestational age (GA) >37 weeks, and weighing ≥2.5 kg (n=3): Received 5 mg/kg on Day 1 and 2.5 mg/kg once daily on subsequent days.
Cohorts 6–7: 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): Received 2.5 mg/kg on Day 1 and 1.25 mg/kg once daily on subsequent days.
The adverse reactions observed were consistent with those observed in clinical trials of VEKLURY in adults.
Infants, children, and adolescents; Cohorts 1–4, 8: Adverse reactions (all grades) were reported in 8 (15%) subjects.
The most common adverse reaction occurring in at least 5% of subjects was ALT increased (6%).
No subjects experienced serious adverse reactions.
Two (4%) subjects permanently discontinued treatment due to adverse reactions (ALT increased [n=1], ALT increased and AST increased and hyperbilirubinemia [n=1]).
Laboratory abnormalities (Grades 3–4) occurring in at least 3% of subjects with COVID-19 receiving VEKLURY in Trial 5823 and who had at least one post-baseline value for the specified test were hemoglobin decreased (18%, 9/51), eGFR decreased (18%, 7/40), creatinine increased (10%, 5/52), direct bilirubin increased (9%, 2/23), prothrombin time increased (7%, 3/46), APTT increased (7%, 3/45), lymphocytes decreased (6% 2/33), proteinuria (6%, 2/36), WBC decreased (4%, 2/51), ALT increased (4%, 2/51), glucose increased (4%, 2/52), glycosuria (4%, 2/46), potassium decreased (4%, 2/52).
Neonates and infants; Cohorts 5–7: Laboratory abnormalities (Grades 3–4) were reported in 3/5 subjects: APTT increased (2/5); direct bilirubin increased (1/5); creatinine increased (1/5); prothrombin time increased (1/5); prothrombin/INR increased (1/5); and potassium increased (1/5).
Emergency Use Authorization Experience in Subjects with COVID-19 The following adverse reactions have been identified during use of VEKLURY under Emergency Use Authorization: General disorders and administration site conditions: Administration site extravasation Skin and subcutaneous tissue disorders: Rash Immune system disorders: Anaphylaxis, angioedema, infusion-related reactions, hypersensitivity Investigations: Transaminase elevations
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc.
at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
Clinical Trials in Adult Subjects The safety of VEKLURY is based on data from four Phase 3 studies in 1,476 hospitalized adult subjects with COVID-19, one Phase 3 study in 279 non-hospitalized adult and pediatric subjects (12 years of age and older weighing at least 40 kg) with mild-to-moderate COVID-19, four Phase 1 studies in 131 healthy adults, and from patients with COVID-19 who received VEKLURY under the Emergency Use Authorization or in a compassionate use program.
Clinical Trials Experience in Adults with COVID-19 NIAID ACTT-1 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized subjects with mild, moderate, and severe COVID-19 treated with VEKLURY (n=532) or placebo (n=516) for up to 10 days.
Subjects treated with VEKLURY received 200 mg on Day 1 and 100 mg once daily on subsequent days [see Clinical Studies (14.1) ] .
The collection of adverse event data in this trial was limited to severe (Grade 3) or potentially life-threatening (Grade 4) adverse events, serious adverse events, adverse events leading to study drug discontinuation, and moderate (Grade 2) severity or higher hypersensitivity reactions.
Rates of adverse reactions (≥ Grade 3), serious adverse reactions, and adverse reactions leading to treatment discontinuation are presented in Table 4.
Table 4 Summary of Adverse Reaction Rates in Hospitalized Subjects with Mild, Moderate, or Severe COVID-19 in NIAID ACTT-1 Types of Adverse Reactions VEKLURY N=532 n (%) Placebo N=516 n (%) Adverse reactions, Grades ≥3 41 (8%) 46 (9%) Serious adverse reactions 2 (0.4%) Seizure (n=1), infusion-related reaction (n=1).
3 (0.6%) Adverse reactions leading to treatment discontinuation 11 (2%) Seizure (n=1), infusion-related reaction (n=1), transaminases increased (n=3), ALT increased and AST increased (n=1), GFR decreased (n=2), acute kidney injury (n=3).
15 (3%) Study GS-US-540-5773 was a randomized, open-label clinical trial in hospitalized subjects with severe COVID-19 treated with VEKLURY 200 mg on Day 1 and 100 mg once daily for 5 (n=200) or 10 days (n=197).
Adverse reactions were reported in 33 (17%) subjects in the 5-day group and 40 (20%) subjects in the 10-day group [see Clinical Studies (14.2) ] .
The most common adverse reactions occurring in at least 5% of subjects in either the VEKLURY 5-day or 10-day group, respectively, were nausea (5% vs 3%), AST increased (3% vs 6%), and ALT increased (2% vs 7%).
Rates of any adverse reactions, serious adverse reactions, and adverse reactions leading to treatment discontinuation are presented in Table 5.
Table 5 Summary of Adverse Reaction Rates in Hospitalized Subjects with Severe COVID-19 in Study 5773 Types of Adverse Reactions VEKLURY 5 Days N=200 n (%) VEKLURY 10 Days N=197 n (%) Any adverse reaction, all Grades 33 (17%) 40 (20%) Serious adverse reactions 3 (2%) Transaminases increased (n=5), hepatic enzyme increased (n=1), hypertransaminasaemia (n=1).
4 (2%) Adverse reactions leading to treatment discontinuation 5 (3%) Transaminases increased (n=4), hepatic enzyme increased (n=2), LFT increased (n=2), hypertransaminasaemia (n=1), ALT increased (n=1), ALT increased and AST increased (n=2), injection site erythema (n=1), rash (n=1).
9 (5%) Study GS-US-540-5774 was a randomized, open-label clinical trial in hospitalized subjects with moderate COVID-19 treated with VEKLURY 200 mg on Day 1 and 100 mg daily for 5 (n=191) or 10 days (n=193), or standard of care (SOC) only (n=200) [see Clinical Studies (14.3) ] .
Adverse reactions were reported in 36 (19%) subjects in the 5-day group and 25 (13%) subjects in the 10-day group.
The most common adverse reaction occurring in at least 5% of subjects in the VEKLURY groups was nausea (7% in the 5-day group, 4% in the 10-day group).
Rates of any adverse reactions, serious adverse reactions, and adverse reactions leading to treatment discontinuation are presented in Table 6.
Table 6 Summary of Adverse Reaction Attribution of events to study drug was not performed for the SOC group.
Rates in Hospitalized Subjects with Moderate COVID-19 in Study 5774 Types of Adverse Reactions VEKLURY 5 Days N=191 n (%) VEKLURY 10 Days N=193 n (%) Any adverse reaction, all Grades 36 (19%) 25 (13%) Serious adverse reactions 1 (<1%) Heart rate decreased.
0 Adverse reactions leading to treatment discontinuation 4 (2%) ALT increased (n=2), ALT increased and AST increased (n=1), hypertransaminasaemia (n=1), blood alkaline phosphatase increased (n=1), rash (n=2), heart rate decreased (n=1).
4 (2%) Study GS-US-540-9012 was a randomized, double-blind, placebo-controlled clinical trial in subjects who were non-hospitalized, 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 treated with VEKLURY (n=279; 276 adults and 3 pediatric subjects 12 years of age and older weighing at least 40 kg) or placebo (n=283; 278 adults and 5 pediatric subjects 12 years of age and older weighing at least 40 kg) for 3 days.
Of the 279 subjects treated with VEKLURY, 227 subjects received at least one dose of VEKLURY at an outpatient facility, 44 subjects received at least one dose of VEKLURY in a home healthcare setting, and 8 subjects received at least one dose of VEKLURY at a skilled nursing facility.
Subjects treated with VEKLURY received 200 mg on Day 1 and 100 mg once daily on subsequent days [see Clinical Studies (14.4) ] .
Adverse reactions (all grades) were reported in 34 (12%) subjects in the VEKLURY group and 25 (9%) subjects in the placebo group.
The most common adverse reaction occurring in at least 5% of subjects in the VEKLURY group was nausea (6%).
There were no serious adverse reactions or adverse reactions leading to treatment discontinuation in either treatment group.
Safety in subjects who received VEKLURY in a home healthcare setting was comparable to that observed in the overall GS-US-540-9012 study population, but these findings are based on limited data.
Less Common Adverse Reactions in Adults from Clinical Trials Clinically significant adverse reactions that were reported in <2% of subjects exposed to VEKLURY in clinical trials are listed below: Hypersensitivity reactions [see Warnings and Precautions (5.1) ].
Generalized seizure Rash Laboratory Abnormalities Study GS-US-399-5505 was a Phase 1, randomized, blinded, placebo-controlled clinical trial in healthy volunteers administered VEKLURY 200 mg on Day 1 and 100 mg for either 4 days or 9 days.
Mild (Grade 1, n=8) to moderate (Grade 2, n=1) elevations in ALT were observed in 9 of 20 subjects receiving 10 days of VEKLURY; the elevations in ALT resolved upon discontinuation of VEKLURY.
No subjects (0 of 9) who received 5 days of VEKLURY had graded increases in ALT.
The frequencies of laboratory abnormalities (Grades 3–4) occurring in at least 3% of subjects with COVID-19 receiving VEKLURY in Trials NIAID ACTT-1, 5773, and 5774 are presented in Table 7, Table 8, and Table 9, respectively.
Table 7 Laboratory Abnormalities (Grades 3–4) Reported in ≥3% of Hospitalized Subjects with Mild, Moderate, or Severe COVID-19 in NIAID ACTT-1 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 10 Days N=532 Placebo N=516 ALT increased 3% 6% AST increased 6% 8% Bilirubin increased 2% 5% Creatinine clearance decreased Based on the Cockcroft-Gault formula.
18% 20% Creatinine increased 15% 16% eGFR decreased 18% 24% Glucose increased 12% 13% Hemoglobin decreased 15% 22% Lymphocytes decreased 11% 18% Prothrombin time increased 9% 4% Table 8 Laboratory Abnormalities (Grades 3–4) Reported in ≥3% of Hospitalized Subjects with Severe COVID-19 in Trial 5773 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 5 Days N=200 VEKLURY 10 Days N=197 ALT increased 6% 8% AST increased 7% 6% Creatinine clearance decreased Based on the Cockcroft-Gault formula.
10% 19% Creatinine increased 5% 15% Glucose increased 11% 8% Hemoglobin decreased 6% 8% Table 9 Laboratory Abnormalities (Grades 3–4) Reported in ≥3% of Hospitalized Subjects with Moderate COVID-19 in Trial 5774 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 5 Days N=191 VEKLURY 10 Days N=193 SOC N=200 SOC=Standard of care.
ALT increased 2% 3% 8% Creatinine clearance decreased Based on the Cockcroft-Gault formula.
2% 5% 8% Glucose increased 4% 3% 2% Hemoglobin decreased 3% 1% 6% The frequencies of laboratory abnormalities (Grades 3–4) occurring in at least 2% of subjects with COVID-19 receiving VEKLURY in Trial GS-US-540-9012 are presented in Table 10.
Table 10 Laboratory Abnormalities (Grades 3–4) Reported in ≥2% of Non-Hospitalized Subjects in Trial 9012 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 3 Days N=279 Placebo N=283 Creatinine clearance decreased Based on the Cockcroft-Gault formula.
6% 2% Creatinine increased 3% 1% Glucose increased 6% 6% Lymphocytes decreased 2% 1% Prothrombin time increased 1% 2% Clinical Trials Experience in Adults with COVID-19 and Renal Impairment Study GS-US-540-5912 was a randomized, double-blind, placebo-controlled clinical trial in which 163 hospitalized subjects with confirmed COVID-19 and acute kidney injury (AKI; N=60), chronic kidney disease (CKD; eGFR <30 mL/minute/1.73m 2 ; N=44), or end-stage renal disease (ESRD; eGFR <15 mL/minute/1.73m 2 ; N=59) on hemodialysis received VEKLURY for up to 5 days [see Use in Specific Populations (8.6) ].
The adverse reactions observed were consistent with those observed in clinical trials of VEKLURY in adults.
Adverse reactions (all grades) were reported in 13 (8%) subjects in the VEKLURY group and 3 (4%) subjects in the placebo group.
The most common adverse reactions were nausea (1%), abdominal pain (1%), and diarrhea (1%).
No subjects experienced serious adverse reactions.
One subject permanently discontinued treatment due to an adverse reaction: lipase increased.
The frequencies of laboratory abnormalities (Grades 3–4) occurring in at least 3% of subjects with COVID-19 receiving VEKLURY in Trial GS-US-540-5912 are presented in Table 11.
Table 11 Laboratory Abnormalities (Grades 3–4) Reported in ≥3% of Hospitalized Subjects in Trial 5912 Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
VEKLURY 5 Days N=163 Placebo N=80 Lymphocytes decreased 27% 27% Hemoglobin decreased 25% 25% Glucose increased 15% 19% Uric acid increased 11% 4% Creatinine increased 12% 14% Albumin decreased 12% 10% Lipase increased 12% 7% Prothrombin time increased 11% 4% Prothrombin INR increased 7% 4% AST increased 6% 4% Thromboplastin time increased 5% 4% ALT increased 5% 6% Sodium increased 3% 3% Calcium increased 3% 0 Clinical Trials in Pediatric Subjects Study GS-US-540-5823 was a Phase 2/3, single-arm, open-label clinical trial in hospitalized subjects from birth to <18 years of age and weighing at least 1.5 kg with mild, moderate, and severe COVID-19 treated with weight-based VEKLURY (n=58) for up to 10 days [see Clinical Studies (14.6) ] : Cohorts 1, 8: Subjects ≥12 years and weighing ≥40 kg (n=12) and subjects <12 years and weighing ≥40 kg (n=5): Received 200 mg on Day 1 and 100 mg once daily on subsequent days.
Cohorts 2–4: 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): Received 5 mg/kg on Day 1 and 2.5 mg/kg once daily on subsequent days.
Cohort 5: Subjects 14 to <28 days old, gestational age (GA) >37 weeks, and weighing ≥2.5 kg (n=3): Received 5 mg/kg on Day 1 and 2.5 mg/kg once daily on subsequent days.
Cohorts 6–7: 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): Received 2.5 mg/kg on Day 1 and 1.25 mg/kg once daily on subsequent days.
The adverse reactions observed were consistent with those observed in clinical trials of VEKLURY in adults.
Infants, children, and adolescents; Cohorts 1–4, 8: Adverse reactions (all grades) were reported in 8 (15%) subjects.
The most common adverse reaction occurring in at least 5% of subjects was ALT increased (6%).
No subjects experienced serious adverse reactions.
Two (4%) subjects permanently discontinued treatment due to adverse reactions (ALT increased [n=1], ALT increased and AST increased and hyperbilirubinemia [n=1]).
Laboratory abnormalities (Grades 3–4) occurring in at least 3% of subjects with COVID-19 receiving VEKLURY in Trial 5823 and who had at least one post-baseline value for the specified test were hemoglobin decreased (18%, 9/51), eGFR decreased (18%, 7/40), creatinine increased (10%, 5/52), direct bilirubin increased (9%, 2/23), prothrombin time increased (7%, 3/46), APTT increased (7%, 3/45), lymphocytes decreased (6% 2/33), proteinuria (6%, 2/36), WBC decreased (4%, 2/51), ALT increased (4%, 2/51), glucose increased (4%, 2/52), glycosuria (4%, 2/46), potassium decreased (4%, 2/52).
Neonates and infants; Cohorts 5–7: Laboratory abnormalities (Grades 3–4) were reported in 3/5 subjects: APTT increased (2/5); direct bilirubin increased (1/5); creatinine increased (1/5); prothrombin time increased (1/5); prothrombin/INR increased (1/5); and potassium increased (1/5).
Emergency Use Authorization Experience in Subjects with COVID-19 The following adverse reactions have been identified during use of VEKLURY under Emergency Use Authorization: General disorders and administration site conditions: Administration site extravasation Skin and subcutaneous tissue disorders: Rash Immune system disorders: Anaphylaxis, angioedema, infusion-related reactions, hypersensitivity Investigations: Transaminase elevations