VEKLURY improved clinical outcomes in hospitalized patients across a spectrum of COVID-19 disease severity1-4
ACTT-1 Study trial design
The ACTT-1 study was a randomized, double-blind, placebo-controlled, phase 3 clinical trial in hospitalized adult patients with confirmed SARS-CoV-2 infection and mild, moderate, or severe COVID-19.
Treatment with VEKLURY® (remdesivir) was stopped in patients who were discharged from the hospital prior to the completion of 10 days of treatment.
Primary endpoint: time to recovery by Day 29 based on ordinal scale
Time to recovery was assessed 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.
Baseline characteristics
| Characteristic | VEKLURY(n=541) | Placebo(n=521) |
|---|---|---|
| Mean age ± SD | 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% |
| 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 the following: mechanical ventilation, oxygen requirement, SpO2 ≤94% on room air, or respiratory rate ≥24 breaths/minute.
VEKLURY helped shorten time to recovery
Patients with COVID-19 experienced significantly shorter recovery times with VEKLURY in the overall study population by Day 29
Recovery, which included hospital discharge for some patients with or without limitations on activities, was defined as ordinals 1 to 3.
8-point ordinal scale
Treatment with VEKLURY earlier in the disease course resulted in the greatest benefit for patients
A prespecified subgroup analysis showed:
- In patients with symptom onset ≤10 days (n=676), median time to recovery was 9 days with VEKLURY vs 15 days with placebo (recovery rate ratio: 1.37 [95% Cl, 1.14-1.64])
- In patients with symptom onset >10 days (n=383), median time to recovery was 11 days with VEKLURY vs 15 days with placebo (recovery rate ratio: 1.20 [95% Cl, 0.94-1.52])
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.
The efficacy of VEKLURY was proven across a variety of secondary clinical endpoints
Patients had a significantly greater likelihood of improvement in clinical status with VEKLURY
- A key secondary endpoint was clinical status of patients on Day 15 as assessed by an 8-point ordinal scale
Patients were
more likely to have improved clinical status
with VEKLURY vs placebo at Day 15
Improvements were maintained through Day 29 (odds ratio: 1.54 [95% CI, 1.25-1.91])
VEKLURY reduced progression to mechanical ventilation or ECMO
(95% CI, 10%-17%)
(95% CI, 19%-27%)
Significantly lower incidence of new mechanical ventilation or ECMO with VEKLURY compared with placebo in patients who were not receiving either at baseline
Mortality in the overall population
Overall mortality was a prespecified secondary endpoint in the ACTT-1 trial
- Results in the overall population at day 29 were not statistically significant
| VEKLURY(n=541)% (n) | Placebo(n=521)% (n) | |
|---|---|---|
| Mortality by Day 15 | 7% (35) | 12% (61) |
| (hazard ratio: 0.55 [95% CI, 0.36-0.83]) | ||
| Mortality by Day 29 | 11% (59) | 15% (77) |
| (hazard ratio: 0.73 [95% CI, 0.52-1.03]) | ||
In a post hoc subgroup analysis, VEKLURY reduced mortality rates in patients on low-flow oxygen at baseline (ordinal score 5), with the difference in other baseline ordinal subgroups not reaching statistical significance
Mortality by ordinal score at baseline
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- There was no adjustment to control for multiple testing in this post hoc analysis
- In other studies, VEKLURY was shown to have no benefit on mortality rates
Adverse reactions in the ACCT-1 trial
- All adverse reactions (ARs), Grades ≥3: 41 (8%) with VEKLURY vs 46 (9%) with placebo; serious ARs: 2 (0.4%)* vs 3 (0.6%); ARs leading to treatment discontinuation: 11 (2%)† vs 15 (3%)
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 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.
Drug interactions
- Drug interaction trials of VEKLURY and other concomitant medications have not been conducted in humans.
Dosage and administration
- Dosage: For adults and pediatric patients ≥12 years old and weighing ≥40 kg: 200 mg on Day 1, followed by once-daily maintenance doses of 100 mg from Day 2 administered only via intravenous infusion. VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
- Treatment duration:
- 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 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 for up to 5 additional days, for a total treatment duration of up to 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.
- 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.
- Dose preparation and administration: See full Prescribing Information.
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 ≥12 years old and weighing ≥40 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 ≥12 years old and weighing ≥40 kg with positive results of SARS-CoV-2 viral testing, who are:
For information about emergency use to treat suspected or laboratory-confirmed COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, please see the EUA Fact Sheet and FDA Letter of Authorization available at gilead.com/remdesivir.
Please see full Prescribing Information for VEKLURY.
COVID-19=coronavirus disease 2019; ECMO=extracorporeal membrane oxygenation; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; SD=standard deviation; SpO2=oxygen saturation.
*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).
View All
INDICATION
View All
Collapse
VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients ≥12 years old and weighing ≥40 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 ≥12 years old and weighing ≥40 kg with positive results of SARS-CoV-2 viral testing, who are:
For information about emergency use to treat suspected or laboratory-confirmed COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, please see the EUA Fact Sheet and FDA Letter of Authorization available at gilead.com/remdesivir.
Please see full Prescribing Information for VEKLURY.
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 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.
Drug interactions
- Drug interaction trials of VEKLURY and other concomitant medications have not been conducted in humans.
Dosage and administration
- Dosage: For adults and pediatric patients ≥12 years old and weighing ≥40 kg: 200 mg on Day 1, followed by once-daily maintenance doses of 100 mg from Day 2 administered only via intravenous infusion. VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
- Treatment duration:
- 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 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 for up to 5 additional days, for a total treatment duration of up to 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.
- 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.
- Dose preparation and administration: See full Prescribing Information.
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.
