– 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).
ACTT-1 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
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. 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.
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 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.
Forward-Looking Statements
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.
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