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Early use of VEKLURY helped prevent progression to COVID-19–related hospitalization or death1,2
VEKLURY significantly reduced risk of progression to severe COVID-191,2
Lower risk of COVID-19–related hospitalization or death from any cause by Day 28
- 0.7% of patients treated with VEKLURY compared to 5.3% of patients treated with placebo had a COVID-19–related hospitalization or death from any cause by Day 28; HR: 0.13 (95% Cl, 0.03 to 0.59), p=0.008
- No deaths were reported in either group by Day 28
The PINETREE study (GS-US-540-9012) was a phase 3, randomized, double-blind, placebo-controlled clinical trial involving patients who were not hospitalized, had confirmed positive results for SARS-CoV-2 infection, showed symptoms of mild-to-moderate COVID-19 for ≤7 days, and had at least 1 risk factor for progression to hospitalization.1,2
Study design1,2
Risk factors included age ≥60 years, obesity (BMI ≥30 kg/m2), 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.
Patients who received, required, or were expected to require supplemental oxygen were excluded from the trial.
Primary endpoints
The primary efficacy endpoint was a composite of COVID-19–related hospitalization (defined as ≥24 hours of acute care) or death from any cause by Day 28. The primary safety endpoint was any adverse event.
R=randomization.
Safety parameters in the PINETREE study1,2
The safety profile was similar between VEKLURY and placebo
The primary safety endpoint of any adverse event was reported in 42.3% of patients treated with VEKLURY vs 46.3% of patients treated with placebo.
- The most common adverse reaction (≥5%) in patients taking VEKLURY was nausea
- There were no serious adverse reactions or adverse reactions leading to treatment discontinuation
Comparable frequency of adverse events vs placebo
| Adverse events* | VEKLURY(n=279)n (%) | Placebo(n=283)n (%) |
|---|---|---|
| Nausea | 30 (10.8) | 21 (7.4) |
| Headache | 16 (5.7) | 17 (6.0) |
| Cough | 10 (3.6) | 18 (6.4) |
| Diarrhea | 11 (3.9) | 11 (3.9) |
| Dyspnea | 7 (2.5) | 15 (5.3) |
| Fatigue | 10 (3.6) | 11 (3.9) |
| Ageusia | 8 (2.9) | 7 (2.5) |
| Anosmia | 9 (3.2) | 6 (2.1) |
| Dizziness | 5 (1.8) | 10 (3.5) |
| Chills | 6 (2.2) | 8 (2.8) |
| Pyrexia | 1 (0.4) | 11 (3.9) |
| COVID-19 pneumonia | 2 (0.7) | 8 (2.8) |
| Serious adverse event† | 5 (1.8) | 19 (6.7) |
| Adverse event leading to discontinuation | 2 (0.7) | 5 (1.8) |
| Death | 0 | 0 |
*Of the 8 patients who were adolescents, 1 patient in the placebo group reported an adverse event (mild fatigue).
†Severity grades were defined according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, dated July 2017.
Laboratory abnormalities (Grades 3–4) reported in ≥2% of nonhospitalized patients
| Laboratory parameter abnormality‡ | VEKLURY(n=279) | Placebo(n=283) |
|---|---|---|
| Creatinine clearance decreased§ | 6% | 2% |
| Creatinine increased | 3% | 1% |
| Glucose increased | 6% | 6% |
| Lymphocytes decreased | 2% | 1% |
| Prothrombin time increased | 1% | 2% |
‡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 characteristics2
| Characteristic | VEKLURY(n=279) | Placebo(n=283) |
|---|---|---|
| Mean age ± SD, y | 50±15 | 51±15 |
| Age, n (%) | ||
| ≥60 y | 83 (29.7) | 87 (30.7) |
| <18 y | 3 (1.1) | 5 (1.8) |
| Female sex, n (%) | 131 (47.0) | 138 (48.8) |
| Residence in skilled nursing facility, n (%) | 8 (2.9) | 7 (2.5) |
| Median duration of symptoms before first infusion (IQR), days | 5 (3-6) | 5 (4-6) |
| Median time since RT-PCR confirmation of SARS-CoV-2 (IQR), days | 2 (1-3) | 3 (1-4) |
| Race or ethnic group, n (%)* | ||
| White | 228 (81.7) | 224 (79.2) |
| Black | 20 (7.2) | 22 (7.8) |
| American Indian or Alaska Native | 15 (5.4) | 21 (7.4) |
| Asian, Native Hawaiian, or Pacific Islander | 7 (2.5) | 7 (2.5) |
| Hispanic or Latinx | 123 (44.1) | 112 (39.6) |
| Other | 3 (1.1) | 2 (0.7) |
| Body mass index, mean ± SD, kg/m2 | 31.2±6.7 | 30.8±5.8 |
| Coexisting conditions, n (%) | ||
| Diabetes mellitus | 173 (62.0) | 173 (61.1) |
| Obesity | 154 (55.2) | 156 (55.1) |
| Hypertension | 138 (49.5) | 130 (45.9) |
| Chronic lung disease | 67 (24.0) | 68 (24.0) |
| Current cancer | 12 (4.3) | 18 (6.4) |
| Cardiovascular or cerebrovascular disease | 20 (7.2) | 24 (8.5) |
| Immune compromise | 14 (5.0) | 9 (3.2) |
| Chronic kidney disease, mild or moderate | 7 (2.5) | 11 (3.9) |
| Chronic liver disease | 1 (0.4) | 1 (0.4) |
*Race and ethnic group were reported by the patients. Patients could have had more than one race or ethnic group.
IQR=interquartile range; RT-PCR=reverse transcription–polymerase chain reaction.
“Remdesivir is another important option for outpatients with COVID-19.”2
See VEKLURY data on disease progression and recovery time
ACTT-1 STUDYSee results for VEKLURY in patients under 18 years old
PEDIATRIC STUDYImportant 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), who are:
VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg), who are:
Please see full Prescribing Information for VEKLURY.
HR=hazard ratio.
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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), who are:
VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg), who are:
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 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.
