– Real-World Evidence from Nearly 100,000 Hospitalized Patients Provides Clinical Insights on the Use of Veklury for the Treatment of COVID-19 –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced positive data from three retrospective studies of the real-world treatment of patients hospitalized with COVID-19, adding to the body of mortality and hospital discharge data for patients treated with Veklury® (remdesivir). Presented at the World Microbe Forum (WMF) this week, all three of the real-world analyses observed that, in the overall patient populations, patients who received Veklury treatment had significantly lower risk for mortality compared with matched controls. A reduction in mortality was observed across a spectrum of baseline oxygen requirements. The results were consistently observed at different timeframes over the course of the pandemic and across geographies. Two of the studies also observed that patients who received Veklury had a significantly increased likelihood of discharge from the hospital by Day 28.
The three real-world data analyses presented at WMF include 98,654 patients hospitalized with COVID-19. Two retrospective studies observed treatment trends and outcomes in the U.S. from the HealthVerity and Premier Healthcare databases. A third analysis compared clinical outcomes in patients receiving a 10-day treatment course of Veklury in the extension phase of the global, open-label SIMPLE-Severe study with patients receiving standard of care in a real-world retrospective longitudinal cohort study. All three analyses utilized pre-specified endpoints, best practice methodologies, including robust matching and weighting approaches, and sensitivity analyses, and were conducted in collaboration with independent experts in real-world comparative effectiveness research. Real-world evidence (RWE) analyses of Veklury from other sources are ongoing and may vary in their results or conclusions.
In the double-blind, placebo-controlled ACTT-1 clinical trial of hospitalized patients with COVID-19, there was a trend toward reduced mortality at Day 29 (11% vs. 15%, HR:0.73, 95% CI:0.52 to 1.03) in Veklury-treated patients (n=541) compared with placebo (n=521) in the overall study population; this result was not statistically significant. Given the range of disease severity in the overall study population, a post-hoc analysis with no adjustment for multiple testing was conducted to determine whether there were differences in mortality based on patients’ baseline clinical status. In this analysis, patients requiring low-flow oxygen at baseline who received Veklury achieved a statistically significant 70% reduction in mortality at Day 29 (4% vs. 13%; HR:0.30, 95% CI:0.14 to 0.64). The difference in mortality in other subgroups based on baseline clinical status was not statistically significant. The effect on mortality observed in other published studies has varied, by both result and analysis method.
“Clinical trials help us understand the efficacy and safety profile of a treatment, but their size can limit our ability to assess all potential aspects of a treatment’s effect due to low event rates in the trials. Large real-world datasets with greater sample sizes and robust methodologies can be helpful to assess treatment effects in both the overall patient population and in clinically relevant subsets of patients,” said Robert L. Gottlieb, MD, PhD, Cardiologist at Baylor University Medical Center and Baylor Scott & White Research Institute. “These real-world analyses provide clinicians with additional data on the efficacy of remdesivir (Veklury) in patients hospitalized with COVID-19, including its effect on mortality and likelihood of discharge from the hospital.”
While randomized clinical trials (RCTs) remain the best tool for assessing the efficacy and safety of a medicine, RWE provides important data on a treatment’s use in clinical practice that can complement data from RCTs. These studies take on greater incremental importance in a pandemic, where clinical management of a disease continues to evolve and can outpace the initiation of new clinical trials, and where frontline healthcare workers are eager for RWE to guide and reinforce treatment decisions in real time. Real-world studies should be interpreted based on the type and size of the source datasets and the methodologies used to mitigate potential confounding or bias. RWE should be considered carefully in context of all available data.
In the United States, Veklury is indicated for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of COVID-19 requiring hospitalization. Veklury is contraindicated in patients who are allergic to Veklury or any of its components; please see below for additional Important Safety Information for Veklury.
Aetion and HealthVerity Analysis (iPoster #WMF21-2970)
This retrospective, real-world comparative analysis of U.S.-based claims data from HealthVerity, performed in collaboration with Aetion, assessed mortality and the likelihood of discharge in hospitalized COVID-19 patients who were treated with Veklury (n=24,856) versus matched controls (n=24,856) between May 1, 2020 and May 3, 2021. Controls were matched 1:1 to patients treated with Veklury using risk set sampling on date of admission, number of days from admission to start of Veklury, age, gender, baseline oxygen support requirement and corticosteroid use. A 1:1 propensity score matching was applied to establish comparable groups based on baseline clinical and demographic characteristics, comorbidities and concomitant medications. The primary endpoint was time to death.
This analysis found that in the overall population, patients receiving Veklury had a statistically significant 23% lower mortality risk compared with controls (HR:0.77, 95% CI:0.73 to 0.81), regardless of baseline oxygen requirement. Overall, a significantly greater likelihood of discharge by Day 28 was observed in patients completing a full five-day course of Veklury compared with controls (HR:1.19, 95% CI:1.14 to 1.25); this result was most pronounced in patients with lower oxygen requirements at baseline.
Premier Analysis (iPoster #WMF21-2507)
This retrospective, real-world comparative analysis of data from the Premier Healthcare Database assessed mortality in hospitalized patients who were treated with Veklury (n=28,855) versus matched patients who were not treated with Veklury (n=16,687) between August and November 2020. The analysis included adult hospitalized patients who were treated with Veklury within the first two days of hospitalization with those not treated with Veklury during their hospitalization. Patients were matched on baseline level of oxygenation, hospital, within a two-month hospital admission period, and all stayed in the hospital for a minimum of three days after initiating treatment. The primary endpoint was time to death.
In this analysis, patients overall who were treated with Veklury had a significantly lower risk of mortality both at Day 14 (HR:0.76, 95% CI:0.70 to 0.83, p<0.0001) and at Day 28 (HR:0.89, 95% CI:0.82 to 0.96, p=0.003) compared with patients who did not receive Veklury. Patients who were treated with Veklury and received either no oxygen (HR:0.69, 95%, CI:0.57 to 0.83, p<0.001), low-flow oxygen (HR:0.68, 95% CI:0.60 to 0.77, p<0.0001) or invasive mechanical ventilation/ECMO (HR:0.70, 95% CI:0.58 to 0.84, p=0.0001) at baseline had a significantly lower risk of 14-day mortality. A significant reduction in mortality was also noted at 28 days for these same groups of patients, no oxygen (HR:0.80, 95%, CI:0.68 to 0.94, p=0.007), low-flow oxygen (HR:0.77, 95% CI:0.68 to 0.86, p<0.0001) or invasive mechanical ventilation/ECMO (HR:0.81, 95% CI:0.69 to 0.94, p=0.007). Patients on high-flow oxygen at baseline who received Veklury also had significantly lower 14-day mortality (HR:0.81, 95% CI:0.70 to 0.93, p=0.0043); at 28 days, the difference in mortality in patients receiving high-flow oxygen at baseline was not statistically significant (HR:0.97, 95% CI:0.84 to 1.11, p=0.646).
SIMPLE-Severe Analysis (iPoster #WMF21-2969)
The SIMPLE-Severe study was a randomized, open-label, multicenter, Phase 3 study in hospitalized adult patients with severe COVID-19 (oxygen saturation of ≥94% on room air, or receiving supplemental oxygen and radiological evidence of pneumonia); these results have been previously presented. As the primary objective of the study was to evaluate five-day and 10-day dosing durations of Veklury, the initial phase of the study did not include a standard of care comparator arm. The retrospective real-world analysis presented at WMF compared mortality outcomes of hospitalized patients with COVID-19 who received Veklury in the open-label extension phase of the SIMPLE-Severe study (n=1,974) versus propensity-score weighted patients from a real-world retrospective longitudinal cohort study of hospitalized patients with COVID-19 who were not treated with Veklury (n=1,426). Propensity score weighting was used to ensure consistent baseline demographics, region, clinical characteristics, concomitant medications and comorbidities. The primary endpoint was time to all-cause death.
This analysis found that in the overall population, treatment with Veklury was associated with a statistically significant 54% lower mortality risk at 28 days versus those not treated with Veklury, regardless of a patient’s baseline oxygen requirements (HR:0.46, 95% CI:0.39 to 0.54, p<0.001). Patients who completed a full 10-day course of Veklury had a significantly shorter time to discharge within 28 days compared with those who did not receive Veklury (HR:1.64, 95% CI:1.43 to 1.87, p<0.001); the result for time to discharge was not significant for patients receiving invasive mechanical ventilation or ECMO at baseline (HR:0.92, 95% CI:0.62 to 1.36, p=0.68).
The global, randomized, double-blind, placebo-controlled, Phase 3 clinical trial ACTT-1 (NTC04280705) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) evaluated the efficacy and safety of a 10-day treatment course of Veklury versus placebo in 1,063 hospitalized adult patients with mild, moderate or severe COVID-19 who also were receiving treatment with standard of care. The primary outcome measure was time to recovery within 29 days after randomization; overall mortality was a prespecified secondary endpoint. Study results and additional mortality data from a post-hoc analysis were published in the New England Journal of Medicine on October 8, 2020. These results have been previously presented.
U.S. Important Safety Information for Veklury
- 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. Monitor patients under close medical supervision for hypersensitivity reactions during and following administration of Veklury. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time ≤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 antiviral activity of Veklury.
- 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 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 over 30 to 120 minutes.
- Treatment duration: For patients not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 5 days; may be extended up to 5 additional days (10 days total) if clinical improvement is not observed. For patients requiring invasive mechanical ventilation and/or ECMO: 10 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: There are insufficient human data on the use of Veklury during pregnancy. Pregnant women hospitalized with COVID-19 are at risk for serious morbidity and mortality. Veklury should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
- 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.
U.S. Indication for Veklury
Veklury® (remdesivir 100 mg for injection) is indicated for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of COVID-19 requiring hospitalization. Veklury should only be administered in a hospital or in a healthcare setting capable of providing acute care comparable to inpatient hospital care.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from ongoing or additional clinical trials or studies, including those involving Veklury; and the possibility that Gilead or other parties may be unable to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, including those involving Veklury. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2021, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements.
U.S. full Prescribing Information for Veklury is available at www.gilead.com.
Veklury, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Jacquie Ross, Investors
Nicole Rodriguez, Media