ACTT-1 study

VEKLURY helped shorten time to recovery and reduced disease progression in patients hospitalized with COVID-191-3

The ACTT-1 study was the first clinical trial in the United States to evaluate treatment for COVID-19. Substantial evidence of efficacy and demonstration of the safety profile led VEKLURY to become the first FDA-approved treatment for COVID-19.4,5

VEKLURY improved clinical outcomes across a spectrum of disease severity in patients hospitalized with COVID-191,2

In the ACTT-1 overall study population, patients experienced

  • The primary endpoint was time to recovery within 29 days after randomization, based on an 8-point ordinal scale
  • Recovery was defined as patients who were no longer hospitalized or hospitalized but no longer required ongoing COVID-19 medical care

ACTT-1 was a randomized, double-blind, placebo-controlled, phase 3 clinical trial in hospitalized adult patients (N=1062) with confirmed SARS-CoV-2 infection and mild, moderate, or severe COVID-19, who received VEKLURY (n=541) or placebo (n=521) for up to 10 days.1

Study design1

A graphic showing the ACCTT-1 study design A graphic showing the ACCTT-1 study design

Treatment with VEKLURY was stopped in patients who were discharged from the hospital prior to the completion of 10 days of treatment.

R=randomization.

Treatment with VEKLURY earlier in the disease course resulted in the greatest benefit for patients1-3

A prespecified subgroup analysis showed:

VEKLURY is indicated for patients hospitalized with COVID-19, independent of time from symptom onset

A post hoc analysis of time to recovery in patients receiving VEKLURY + corticosteroids vs corticosteroids alone2,3

A bar graph showing the recovery time in patients when receiving VEKLURY® (remdesivir) A bar graph showing the recovery time in patients when receiving VEKLURY® (remdesivir)

Median 9 days with VEKLURY + corticosteroids vs 14 days with corticosteroids alone; recovery rate ratio: 1.28 (95% Cl, 1.09 to 1.50)

IMPORTANT SAFETY INFORMATION

Contraindication

  • VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.

Please see additional Important Safety Information below.

VEKLURY helped improve clinical status and shorten time on oxygen1-3

Patients had a significantly greater likelihood of improvement in clinical status with VEKLURY

VEKLURY reduced median time on oxygen in patients who received oxygen at baseline2

Days on oxygen with VEKLURY® (remdesivir) Days on oxygen with VEKLURY® (remdesivir)

VEKLURY helped reduce progression to severe disease, an additional secondary endpoint1-3

VEKLURY reduced incidence of new noninvasive ventilation or high-flow oxygen vs placebo in patients who did not receive either at baseline

Incidence of progression with VEKLURY® (remdesivir) vs. placebo Incidence of progression with VEKLURY® (remdesivir) vs. placebo

VEKLURY reduced incidence of new mechanical ventilation or ECMO vs placebo in patients who did not receive either at baseline

Incidence of progression with VEKLURY® (remdesivir) Incidence of progression with VEKLURY® (remdesivir)

Mortality in overall population1,2

Mortality at Day 29 was a prespecified secondary endpoint

Results in the overall population at Day 29 were not statistically significant.

Mortality rate at day 15 with patients using VEKLURY® (remdesivir) Mortality rate at day 15 with patients using VEKLURY® (remdesivir)
Mortality rate at day 29 with patients using VEKLURY® (remdesivir) Mortality rate at day 29 with patients using VEKLURY® (remdesivir)

Mortality rates by ordinal scale at Day 29, a post hoc subgroup analysis1-3

ACTT-1 Study data showing the number of patients and deaths ACTT-1 Study data showing the number of patients and deaths
  • VEKLURY reduced mortality rates at Day 29 in patients on low-flow oxygen at baseline by 70% vs placebo. HR: 0.30 (95% Cl, 0.14 to 0.64)
  • No difference was demonstrated in the other baseline oxygen status subgroups
  • There was no adjustment to control for multiple testing in this post hoc analysis

Safety parameters in the ACTT-1 study1

Adverse reaction frequency and laboratory abnormalities were comparable between VEKLURY and placebo

Comparable frequency of adverse reactions vs placebo

Types of adverse reactions VEKLURY(n=532)n (%) Placebo(n=516)n (%)
Any adverse reaction, Grades ≥3 41 (8) 46 (9)
Serious adverse reactions 2 (0.4)* 3 (0.6)
Adverse reactions leading to treatment discontinuation 11 (2) 15 (3)

*Seizure (n=1), infusion-related reaction (n=1).

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).

Laboratory abnormalities (Grades 3–4) reported in ≥3% of patients

Laboratory parameter abnormality VEKLURY(n=532) Placebo(n=516)
ALT increased 3% 6%
AST increased 6% 8%
Bilirubin increased 2% 5%
Creatinine clearance decreased§ 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%

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.

§Based on the Cockcroft-Gault formula.

Baseline characteristics1,2

Characteristic VEKLURY(n=541) Placebo(n=521)
Median age ± SD, y 58.6±14.6 59.2±15.4
Male sex 65.1% 63.7%
Race
White 51.6% 55.1%
Black 20.1% 22.5%
Asian 14.6% 10.7%
Ethnicity: Hispanic/Latinx 24.8% 22.3%
Mild/moderate disease* 10% 10%
Severe disease 90% 90%
Median time from symptom onset to randomization (IQR), days 9 (6-12) 9 (7-13)
Respiratory status
Low-flow oxygen 42.9% 39.0%
High-flow oxygen 17.6% 18.8%
Invasive mechanical ventilation/ECMO 24.2% 29.6%
Comorbidities
Hypertension 50.6% 50.9%
Obesity 45.6% 45.2%
Type 2 diabetes mellitus 30.8% 30.4%

*Defined by SpO2 >94% and respiratory rate <24 breaths/minute without supplemental oxygen.

Defined by a requirement for mechanical ventilation, oxygen requirement, SpO2 ≤94% on room air, or respiratory rate ≥24 breaths/minute.

Data on symptom onset were missing for 3 patients.

ECMO=extracorporeal membrane oxygenation; IQR=interquartile range; SpO2=oxygen saturation.

8-point ordinal scale1,2

Patient clinical status was assessed on an 8-point ordinal scale with a higher score indicating greater clinical severity.

A graphic showing the patient's clinical status assessed on an 8-point ordinal scale A graphic showing the patient's clinical status assessed on an 8-point ordinal scale

ECMO=extracorporeal membrane oxygenation.

See clinical outcomes for VEKLURY in high-risk patients

OUTPATIENT STUDY

See results for VEKLURY in patients under 18 years old

PEDIATRIC STUDY

Important Safety Information

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Contraindication

  • VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.

Warnings and precautions

  • Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of VEKLURY; most reactions occurred within 1 hour. Monitor patients during infusion and observe for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time of up to 120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue VEKLURY and initiate appropriate treatment (see Contraindications).
  • Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received VEKLURY; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing VEKLURY if ALT levels increase to >10x ULN. Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.
  • Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in the antiviral activity of VEKLURY.

Adverse reactions

  • The most common adverse reaction (≥5% all grades) was nausea.
  • The most common lab abnormalities (≥5% all grades) were increases in ALT and AST.

Dosage and administration

  • Administration should take place under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible.
  • Treatment duration:
    • For patients who are hospitalized, VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
    • For patients who are hospitalized and do not require invasive mechanical ventilation and/or ECMO, the recommended treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended up to 5 additional days, for a total treatment duration of up to 10 days.
    • For patients who are hospitalized and require invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days.
    • For patients who are not hospitalized, diagnosed with mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death, the recommended total treatment duration is 3 days. VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19 and within 7 days of symptom onset for outpatient use.
  • Testing prior to and during treatment: Perform eGFR, hepatic laboratory, and prothrombin time testing prior to initiating VEKLURY and during use as clinically appropriate.
  • Renal impairment: VEKLURY is not recommended in individuals with eGFR <30 mL/min.

Pregnancy and lactation

  • Pregnancy: A pregnancy registry has been established. There are insufficient human data on the use of VEKLURY during pregnancy. COVID-19 is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.
  • Lactation: It is not known whether VEKLURY can pass into breast milk. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

INDICATION

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VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg) with positive results of SARS-CoV-2 viral testing, who are: VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg) with positive results of SARS-CoV-2 viral testing, who are:

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

ECMO=extracorporeal membrane oxygenation; HR=hazard ratio.

References: 1. Veklury. Prescribing Information. Gilead Sciences, Inc.; 2022. 2. Beigel JH, Tomashek KM, Dodd LE; ACTT-1 Study Group Members. Remdesivir for the treatment of COVID-19—final report. N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa2007764 3. Beigel JH, Tomashek KM, Dodd LE, et al; ACTT-1 Study Group. Remdesivir for the treatment of COVID-19—final report. Supplementary appendix. N Engl J Med. 2020;383(19):1813-1826. Accessed August 16, 2022. https://www.nejm.org/doi/suppl/10.1056/NEJMoa2007764/suppl_file/nejmoa2007764_appendix.pdf 4. NIH clinical trial of remdesivir to treat COVID-19 begins. News release. National Institutes of Health. February 25, 2020. Accessed August 16, 2022. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins 5. FDA approves first treatment for COVID-19. News release. US Food and Drug Administration. October 22, 2020. Accessed August 16, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19


View All

INDICATION

View All

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VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg) with positive results of SARS-CoV-2 viral testing, who are: VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg) with positive results of SARS-CoV-2 viral testing, who are:

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

Important Safety Information

Collapse

Contraindication

  • VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.

Warnings and precautions

  • Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of VEKLURY; most reactions occurred within 1 hour. Monitor patients during infusion and observe for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time of up to 120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue VEKLURY and initiate appropriate treatment (see Contraindications).
  • Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received VEKLURY; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing VEKLURY if ALT levels increase to >10x ULN. Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.
  • Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in the antiviral activity of VEKLURY.

Adverse reactions

  • The most common adverse reaction (≥5% all grades) was nausea.
  • The most common lab abnormalities (≥5% all grades) were increases in ALT and AST.

Dosage and administration

  • Administration should take place under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible.
  • Treatment duration:
    • For patients who are hospitalized, VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
    • For patients who are hospitalized and do not require invasive mechanical ventilation and/or ECMO, the recommended treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended up to 5 additional days, for a total treatment duration of up to 10 days.
    • For patients who are hospitalized and require invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days.
    • For patients who are not hospitalized, diagnosed with mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death, the recommended total treatment duration is 3 days. VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19 and within 7 days of symptom onset for outpatient use.
  • Testing prior to and during treatment: Perform eGFR, hepatic laboratory, and prothrombin time testing prior to initiating VEKLURY and during use as clinically appropriate.
  • Renal impairment: VEKLURY is not recommended in individuals with eGFR <30 mL/min.

Pregnancy and lactation

  • Pregnancy: A pregnancy registry has been established. There are insufficient human data on the use of VEKLURY during pregnancy. COVID-19 is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.
  • Lactation: It is not known whether VEKLURY can pass into breast milk. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

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