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-- Long-Term Data In Treatment-Naïve Patients Highlight Stribild’s
Sustained Efficacy, Safety and Tolerability Profile --
BRUSSELS--(BUSINESS WIRE)--Oct. 16, 2013--
Gilead Sciences, Inc. (Nasdaq: GILD) today announced three-year
(144-week) efficacy and safety results from two pivotal Phase 3 studies
(Studies 102 and 103) evaluating the once-daily single tablet regimen
Stribild® (elvitegravir 150 mg/cobicistat 150
mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) among
treatment-naïve patients with HIV-1 infection. Data show that after
three years of treatment, Stribild demonstrated comparable efficacy to
two standard-of-care HIV regimens, Atripla® (efavirenz 600
mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) in Study
102 and a protease inhibitor-based regimen of ritonavir-boosted
atazanavir plus Truvada® (emtricitabine and tenofovir
disoproxil fumarate) in Study 103. These data are being presented this
week at the 14th European AIDS Clinical Society Conference (EACS) in
“HIV has become a chronic disease that can be managed with life-long
therapy, increasing the need for convenient, once-daily treatment
options that offer long-term efficacy and tolerability,” said Jürgen
Rockstroh, MD, Professor of Medicine, University of Bonn, Germany. “In
these large-scale clinical trials, Stribild demonstrated high and
durable viral suppression and a favorable safety profile over three
years of therapy. These results support Stribild as an important
single-tablet treatment option for people starting antiretroviral
Study 102 found that, at 144 weeks of treatment, 80 percent of Stribild
patients (n=279/348) compared to 75 percent of patients receiving
Atripla (n=265/352) achieved HIV RNA (viral load) less than 50 copies/mL
based on the FDA snapshot algorithm (95 percent CI for the difference:
-1.3 to 11.1 percent for Stribild vs. Atripla).
Similarly, in Study 103, 78 percent of Stribild patients (n=274/353)
versus 75 percent of patients taking a protease inhibitor-based regimen
of ritonavir-boosted atazanavir plus Truvada (n=265/355) achieved HIV
RNA less than 50 copies/mL (95 percent CI for the difference: -3.2 to
9.4 percent for Stribild vs. the atazanavir-based regimen).
In both studies, rates of discontinuation due to adverse events were
similar across all treatment groups (6 percent for Stribild in each
study, 8 percent for Atripla and 9 percent for the atazanavir-based
In Study 102, the most common adverse events occurring in at least 10
percent of Stribild patients were diarrhea, nausea and upper respiratory
tract infection, and for Atripla, they were abnormal dreams, dizziness
and diarrhea. Stribild was associated with numerically lower rates of
certain neuropsychiatric side effects compared to Atripla through 144
weeks, including abnormal dreams (16 percent for Stribild vs. 29 percent
for Atripla), dizziness (8 percent vs. 26 percent) and insomnia (12
percent vs. 17 percent). The frequency of laboratory abnormalities was
comparable between study regimens. Patients taking Stribild also
experienced significantly lower increases in total cholesterol and LDL
(low-density lipoprotein, or “bad” cholesterol) compared to patients
In Study 103, Grade 3-4 laboratory abnormalities were generally similar
for both treatment regimens, with the exception of hyperbilirubinemia,
the rate of which was lower among patients taking Stribild compared to
those taking the atazanavir-based regimen through 144 weeks of treatment
(2 percent vs. 69 percent). In addition, patients taking Stribild in
Study 103 experienced a lower change from baseline in spine bone mineral
density compared to atazanavir patients (-1.43 percent vs. -3.68 percent
, p=0.018), and a similar median change from baseline in hip bone
mineral density (-2.83 percent for Stribild and -3.77 percent for the
atazanavir-based regimen, p=0.23).
Stribild has a Boxed Warning on the risks of lactic acidosis/severe
hepatomegaly with steatosis and post treatment acute exacerbation of
hepatitis B; see below for important safety information.
Stribild was approved by the U.S. Food and Drug Administration in August
2012 and by the European Commission in May 2013.
Study 102 is a randomized (1:1), double-blind Phase 3 clinical trial
comparing the efficacy, safety and tolerability of Stribild (n=348)
versus Atripla (n=352) among HIV-infected treatment-naïve adults with
HIV RNA levels greater than or equal to 5,000 copies/mL. The primary
endpoint of the study is the proportion of patients achieving HIV RNA
levels less than 50 copies/mL at 48 weeks of treatment, per the FDA
snapshot algorithm. Secondary objectives are to evaluate the efficacy,
safety and tolerability of the treatment regimens through 192 weeks of
At baseline, patients in the Stribild arm had a median HIV RNA of 4.75
log10 copies/mL and mean CD4 cell count of 391 cells/mm3.
Patients in the Atripla arm had a median HIV RNA of 4.78 log10
copies/mL and mean CD4 cell count of 382 cells/mm3.
Thirty-four percent of Stribild patients and 33 percent of Atripla
patients had HIV RNA greater than 100,000 copies/mL. Twelve percent of
Stribild patients and 14 percent of Atripla patients had CD4 counts less
than or equal to 200 cells/mm3.
Mean increases in CD4 cell counts were 321 cells/mm3 for
Stribild patients and 300 cells/mm3 for Atripla patients at
144 weeks. Virologic failure rates were seven percent for Stribild and
10 percent for Atripla based on a component of the FDA snapshot analysis.
Through 144 weeks, six percent of Stribild patients and eight percent of
Atripla patients discontinued treatment due to adverse events. Adverse
events leading to treatment discontinuation among patients taking
Stribild were renal events (2.3 percent), depression (0.3 percent) and
fatigue (0.3 percent), and among patients taking Atripla, they were
depression (1.4 percent), rash events and drug hypersensitivity (1.4
percent), fatigue (0.6 percent), abnormal dreams (0.6 percent), insomnia
(0.6 percent) and anxiety (0.6 percent).
The frequency of Grade 3-4 adverse events and laboratory abnormalities
was comparable between study regimens. Median changes from baseline in
total cholesterol and LDL at 144 weeks were significantly smaller for
Stribild compared to Atripla and were, respectively, +14 and +13 mg/dL
for Stribild and +22 and +19 mg/dL for Atripla (total cholesterol,
p=0.007; LDL, p=0.007). Median changes from baseline in HDL
(high-density lipoprotein or “good” cholesterol) and triglycerides were
similar for both treatment arms and were, respectively, +7 mg/dL and +9
mg/dL for Stribild and +9 mg/dL and +5 mg/dL for Atripla (HDL, p=0.021;
Median increases from baseline to 144 weeks in serum creatinine were
0.14 mg/dL for Stribild and 0.01 mg/dL for Atripla. There were four
cases of proximal renal tubulopathy among Stribild patients reported in
the first 48 weeks and none between weeks 48 and 144 weeks. Between 96
and 144 weeks of treatment, one Stribild patient discontinued treatment
due to an isolated rise in creatinine without features of proximal renal
tubulopathy, and the patient improved after treatment discontinuation.
There were no cases of resistance observed with Stribild between weeks
96 and 144.
Study 103 is a randomized (1:1), double-blind Phase 3 clinical trial
comparing the efficacy, safety and tolerability of Stribild (n=353)
versus atazanavir 300 mg boosted by ritonavir 100 mg plus Truvada
(n=355) among HIV-infected treatment-naïve adults with baseline HIV RNA
levels greater than 5,000 copies/mL. The primary endpoint of the study
is the proportion of patients achieving HIV RNA levels less than 50
copies/mL at 48 weeks of treatment, per the FDA snapshot algorithm.
Secondary objectives are to evaluate the efficacy, safety and
tolerability of the treatment regimens through 192 weeks of treatment.
At baseline, patients in the Stribild arm had a median HIV RNA of 4.88
log10 copies/mL and mean CD4 cell count of 364 cells/mm3.
Patients in the atazanavir-based arm had a median HIV RNA of 4.86 log10
copies/mL and mean CD4 cell count of 375 cells/mm3. Forty-two
percent of Stribild patients and 40 percent of atazanavir patients had
HIV RNA greater than 100,000 copies/mL. Fifteen percent of Stribild
patients and 11 percent of atazanavir patients had CD4 counts less than
or equal to 200 cells/mm3.
Patients in the Stribild arm experienced a mean increase of 280 cells/mm3
in CD4 cell count at 144 weeks and patients on the atazanavir-based
regimen had a mean increase of 293 cells/mm3. Virologic
failure rates were eight percent for Stribild and seven percent for the
atazanavir-based regimen based on a component of the FDA snapshot
Through 144 weeks, six percent of Stribild patients and nine percent of
patients on the atazanavir-based regimen discontinued treatment due to
adverse events. Adverse events leading to treatment discontinuation
among patients taking Stribild were renal events (1.4 percent),
hepatitis C (0.6 percent), diarrhea (0.6 percent), pyrexia (0.6
percent), nausea (0.3 percent), vomiting (0.3 percent) and fatigue (0.3
percent). The most common adverse events leading to treatment
discontinuation among patients taking the atazanavir-based regimen were
renal events (2.3 percent), nausea (1.1 percent), ocular icterus (1.1
percent), vomiting (0.6 percent), fatigue (0.6 percent), jaundice (0.6
percent), dizziness (0.6 percent), drug eruption (0.6 percent),
hepatitis C (0.3 percent), diarrhea (0.3 percent) and pyrexia (0.3
percent). The most common adverse events occurring in at least 10
percent of patients in either treatment arm were diarrhea, nausea and
upper respiratory tract infection.
With the exception of hyperbilirubenemia among atazanavir patients,
Grade 3-4 laboratory abnormalities were similar for both treatment
regimens. Median changes from baseline in total cholesterol, HDL and LDL
at 144 weeks were similar for Stribild and the atazanavir-based regimen
and were, respectively, +20, +8 and +17 mg/dL for Stribild, and +16, +7
and +18 mg/dL for the atazanavir-based regimen (total cholesterol,
p=0.30; HDL, p=0.39; LDL, p=0.98). The median change in triglycerides
was +15 mg/dL for Stribild and +22 mg/dL for the atazanavir-based
Both regimens had comparable renal profiles, with median increases from
baseline to 144 weeks in serum creatinine of 0.12 mg/dL for Stribild and
0.08 mg/dL for the atazanavir-based regimen. Through 144 weeks, no
patients taking Stribild and three patients taking the atazanavir-based
regimen discontinued treatment due to proximal renal tubulopathy.
Between 96 and 144 weeks of treatment, two Stribild patients and one
atazanavir patient discontinued treatment due to an isolated rise in
creatinine without features of proximal renal tubulopathy.
There were two cases of resistance observed in both the Stribild and
atazanavir-based arms between weeks 96 and 144.
Studies 102 and 103 are ongoing in a blinded fashion. After week 192,
patients will continue to take their blinded study drug until treatment
assignments have been unblinded. Additional information about the study
can be found at www.clinicaltrials.gov.
Stribild contains four Gilead compounds in a complete once-daily, single
tablet regimen: elvitegravir 150 mg; cobicistat 150 mg; emtricitabine
200 mg; and tenofovir disoproxil fumarate 300 mg. Stribild is indicated
in the United States as a complete regimen for the treatment of HIV-1
infection in adults who are antiretroviral treatment-naïve. Stribild
does not cure HIV-1 infection.
Elvitegravir is a member of the integrase inhibitor class of
antiretroviral compounds. Integrase inhibitors interfere with HIV
replication by blocking the ability of the virus to integrate into the
genetic material of human cells. Elvitegravir was licensed by Gilead
from Japan Tobacco Inc. (JT) in March 2005. Under the terms of Gilead’s
agreement with JT, Gilead has exclusive rights to develop and
commercialize elvitegravir in all countries of the world, excluding
Japan, where JT retains rights.
Cobicistat is Gilead’s proprietary potent mechanism-based inhibitor of
cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body.
On September 25, 2013, cobicistat was approved by the European
Commission under the tradename Tybost®. On September 20,
2013, the Committee for Medicinal Products for Human Use, the scientific
committee of the European Medicines Agency, adopted a positive opinion
on Gilead’s Marketing Authorisation Application (MAA) for elvitegravir.
Elvitegravir as a standalone agent and cobicistat as a standalone agent
in the United States are investigational products and their safety and
efficacy have not been established.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and
POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
Warnings and precautions
Dosage and administration
Pregnancy and breastfeeding
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops
and commercializes innovative therapeutics in areas of unmet medical
need. The company’s mission is to advance the care of patients suffering
from life-threatening diseases worldwide. Headquartered in Foster City,
California, Gilead has operations in North America, Europe and Asia
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 risk
that healthcare providers may not recognize the benefits of Stribild. In
addition, as Stribild is used over longer periods of time by many
patients with underlying health problems taking numerous other
medicines, Gilead may find new issues such as safety, resistance or drug
interaction issues, which may require it to provide additional warnings
or contraindications on the label or narrow Stribild’s approved
indication, each of which could reduce the market acceptance of
Stribild. In addition, regulatory authorities including in the European
Union may not approve our marketing application for elvitegravir, and
the FDA may not approve marketing applications for elvitegravir and/or
cobicistat. Further, even if marketing approval is granted for any of
these products, there may be significant limitations on their use. These
risks, uncertainties and other factors could cause actual results to
differ materially from those referred to in the forward-looking
statements. The reader is cautioned not to rely on these forward-looking
statements. These and other risks are described in detail in Gilead’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2013, as
filed with the U.S. Securities and Exchange Commission. All
forward-looking statements are based on information currently available
to Gilead, and Gilead assumes no obligation to update any such
U.S. full prescribing information for Stribild, Atripla, and Truvada
is available at www.gilead.com.
EU Summary of Product Characteristics for Stribild, Atripla and
Truvada is available at www.ema.europa.eu
Stribild and Truvada are registered trademarks of Gilead Sciences,
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead
For more information on Gilead Sciences, please visit the company’s
website at www.gilead.com,
follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
Source: Gilead Sciences, Inc.
Gilead Sciences, Inc.Patrick O’Brien, 650-522-1936 (Investors)Cara
Miller, 650-522-1616 (Media, U.S.)Stephen Head, +44 208-587-2359