Gilead’s Single Tablet HIV Regimen Stribild® Demonstrates Durable Viral
Suppression Through Three Years of Therapy
-- Long-Term Data In Treatment-Naïve Patients Highlight Stribild’s Sustained
Efficacy, Safety and Tolerability Profile --
14th European AIDS Clinical Society Conference
BRUSSELS -- October 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 Brussels, Belgium.
“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 regimen).
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 taking Atripla.
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 treatment.
At baseline, patients in the Stribild arm had a median HIV RNA of 4.75 log
copies/mL and mean CD4 cell count of 391 cells/mm^3. Patients in the Atripla
arm had a median HIV RNA of 4.78 log copies/mL and mean CD4 cell count of
382 cells/mm^3. 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/mm^3.
Mean increases in CD4 cell counts were 321 cells/mm^3 for Stribild patients
and 300 cells/mm^3 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; triglycerides, p=0.72).
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
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
At baseline, patients in the Stribild arm had a median HIV RNA of 4.88 log
copies/mL and mean CD4 cell count of 364 cells/mm^3. Patients in the
atazanavir-based arm had a median HIV RNA of 4.86 log copies/mL and mean
CD4 cell count of 375 cells/mm^3. 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/mm^3.
Patients in the Stribild arm experienced a mean increase of 280 cells/mm^3 in
CD4 cell count at 144 weeks and patients on the atazanavir-based regimen had a
mean increase of 293 cells/mm^3. Virologic failure rates were eight percent
for Stribild and seven percent for the atazanavir-based regimen based on a
component of the FDA snapshot analysis.
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
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 regimen (p=0.24).
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
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
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
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
*Lactic acidosis and severe hepatomegaly with steatosis, including fatal
cases, have been reported with the use of nucleoside analogs, including
tenofovir disoproxil fumarate (tenofovir DF), a component of Stribild, in
combination with other antiretrovirals.
*Stribild is not approved for the treatment of chronic hepatitis B virus
(HBV) infection and the safety and efficacy of Stribild have not been
established in patients coinfected with HBV and HIV-1. Severe acute
exacerbations of hepatitis B have been reported in patients who are
coinfected with HBV and HIV-1 and have discontinued emtricitabine or
tenofovir DF, components of Stribild. Hepatic function should be monitored
closely with both clinical and laboratory follow-up for at least several
months in patients who are coinfected with HIV-1 and HBV and discontinue
Stribild. If appropriate, initiation of anti-hepatitis B therapy may be
*Coadministration: Do not use with drugs highly dependent on CYP3A for
clearance and for which elevated plasma concentrations are associated with
serious and/or life-threatening events. Do not use with drugs that
strongly induce CYP3A as this may lead to loss of efficacy and possible
resistance to Stribild. Use with the following drugs is contraindicated:
alfuzosin, rifampin, dihydroergotamine, ergotamine, methylergonovine,
cisapride, lovastatin, simvastatin, pimozide, sildenafil for pulmonary
arterial hypertension, triazolam, oral midazolam, and St. John’s wort.
Warnings and precautions
*New onset or worsening renal impairment: Cases of acute renal failure and
Fanconi syndrome have been reported with the use of tenofovir DF and
Stribild. Monitor estimated creatinine clearance (CrCl), urine glucose,
and urine protein in all patients prior to initiating and during therapy;
additionally monitor serum phosphorus in patients with or at risk for
renal impairment. Cobicistat may cause modest increases in serum
creatinine and modest declines in CrCl without affecting renal glomerular
function; patients with an increase in serum creatinine >0.4 mg/dL from
baseline should be closely monitored for renal safety. Do not initiate
Stribild in patients with CrCl below 70 mL/min. Discontinue Stribild if
CrCl declines below 50 mL/min. Avoid concurrent or recent use with a
*Other antiretroviral products: Stribild is a complete regimen for the
treatment of HIV-1 infection. Do not coadminister with other
antiretroviral products, including products containing any of the same
active components; products containing lamivudine; products containing
ritonavir; or with adefovir dipivoxil.
*Decreases in bone mineral density (BMD) and cases of osteomalacia have
been seen in patients treated with tenofovir DF. Consider monitoring BMD
in patients with a history of pathologic fracture or risk factors for bone
*Fat redistribution and accumulation have been observed in patients
receiving antiretroviral therapy.
*Immune reconstitution syndrome, including the occurrence of autoimmune
disorders with variable time to onset, has been reported.
*Common adverse drug reactions in clinical studies (incidence ≥5%; all
grades) were nausea (16%), diarrhea (12%), abnormal dreams (9%), and
*CYP3A substrates: Stribild can alter the concentration of drugs
metabolized by CYP3A or CYP2D6. Do not use with drugs highly dependent on
these factors for clearance and for which elevated plasma concentrations
are associated with serious and/or life-threatening adverse events.
*CYP3A inducers: Drugs that induce CYP3A can decrease the concentrations of
components of Stribild. Do not use with drugs that strongly induce CYP3A
as this may lead to loss of virologic response and possible resistance to
*Drugs affecting renal function: Coadministration of Stribild with drugs
that reduce renal function or compete for active tubular secretion may
increase concentrations of emtricitabine and tenofovir and the risk of
*Antacids: Separate Stribild and antacid administration by at least 2
*Prescribing information: Consult the full prescribing information for
Stribild for more information on potentially significant drug
interactions, including clinical comments.
Dosage and administration
*Adult dosage: One tablet taken orally once daily with food.
*Renal impairment: Do not initiate in patients with CrCl below 70 mL/min.
Discontinue in patients with CrCl below 50 mL/min.
*Hepatic impairment: Not recommended in patients with severe hepatic
*Testing prior to initiation: Test patients for HBV infection and document
baseline CrCl, urine glucose, and urine protein.
Pregnancy and breastfeeding
*Pregnancy Category B: There are no adequate and well-controlled studies in
pregnant women. Use during pregnancy only if the potential benefit
justifies the potential risk. An Antiretroviral Pregnancy Registry has
*Breastfeeding: Emtricitabine and tenofovir have been detected in human
milk. Because of both the potential for HIV transmission and the potential
for serious adverse reactions in nursing infants, mothers should be
instructed not to breastfeed.
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 Pacific.
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 forward-looking
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, Inc.
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences,
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.
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media, U.S.)
Stephen Head, +44 208-587-2359 (Media, Europe)
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