Gilead’s Once-Daily Single Tablet Regimen StribildTM Maintains High Viral
Suppression Through Two Years of Therapy Among Treatment-Naïve HIV Patients
-- Pivotal Data from Two Phase 3 Studies Highlight Stribild’s Sustained
Efficacy, Safety and Tolerability Profile --
GLASGOW, England -- November 15, 2012
Gilead Sciences (Nasdaq:GILD) today announced two-year (96-week) results from
two pivotal Phase 3 studies (Studies 102 and 103) evaluating the company’s
newest single tablet HIV regimen, Stribild^TM (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 Stribild was
non-inferior after two years of treatment 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-based regimen of
ritonavir-boosted atazanavir plus Truvada^® (emtricitabine and tenofovir
disoproxil fumarate) in Study 103. These results were presented today in an
oral session at the 11th International Congress on Drug Therapy in HIV
Infection (HIV11) in Glasgow, United Kingdom.
“In these studies, Stribild demonstrated a robust clinical profile, including
sustained efficacy, safety and resistance results over two years of
treatment,” said Jürgen Rockstroh, MD, Professor of Medicine, University of
Bonn, Germany and a lead investigator for Study 103. “Stribild was also
associated with a lower incidence of certain central nervous system side
effects compared to Atripla, and had a favorable triglycerides profile versus
the atazanavir-based regimen.”
Stribild combines four compounds in one daily tablet: elvitegravir, an
integrase inhibitor; cobicistat, a pharmacoenhancing agent; emtricitabine and
tenofovir disoproxil fumarate. The regimen was approved by the U.S. Food and
Drug Administration (FDA) on August 27, 2012 for use by treatment-naïve
HIV-positive adults based on 48-week results from Studies 102 and 103. A
marketing application for Stribild is currently under review in the European
Study 102 found that at 96 weeks of treatment, 84 percent of Stribild patients
(n=293/348) and 82 percent of Atripla patients (n=287/352) achieved HIV RNA
(viral load) < 50 copies/mL, based on the FDA snapshot algorithm (95 percent
CI for the difference: -2.9 to +8.3 percent for Stribild vs. Atripla;
predefined criterion for non-inferiority was a lower bound of a two sided 95
percent CI of -12 percent).
Similarly, results from Study 103 show that 83 percent of Stribild patients
(n=294/353) and 82 percent of patients receiving the atazanavir-based regimen
(n=292/355) achieved HIV RNA < 50 copies/mL, based on the FDA snapshot
algorithm (95 percent CI for the difference: -4.5 to +6.7 percent for Stribild
vs. the atazanavir-based regimen; predefined criterion for non-inferiority was
a lower bound of a two sided 95 percent CI of -12 percent).
In both Studies 102 and 103, rates of discontinuation due to adverse events
were similar across all treatment groups (5 percent for Stribild in each
study, 7 percent for Atripla and 6 percent for the atazanavir-based regimen).
The most common adverse events occurring in at least 10 percent of Stribild
patients in Study 102 were diarrhea, nausea, upper respiratory infection,
headache, abnormal dreams, fatigue, depression and insomnia; in Study 103,
they were diarrhea, nausea, upper respiratory infection, headache,
nasopharyngitis, depression, back pain and fatigue. In Study 102, there were
consistently higher reports at each study visit through 96 weeks of abnormal
dreams and dizziness in the Atripla arm, with 14 percent and 4 percent of
patients experiencing abnormal dreams and dizziness, respectively, on the
Atripla arm vs. 8 percent and 1 percent, respectively on the Stribild arm at
96 weeks. Similarly, in Study 103, reports of diarrhea were consistently
higher through 96 weeks of treatment on the atazanavir-based arm compared to
Stribild, with 4 percent of Stribild patients vs. 9 percent of patients on an
atazanavir-based regimen experiencing this problem at 96 weeks.
The frequency of Grade 3-4 adverse events and laboratory abnormalities was
also comparable between study regimens. However, in Study 102, patients taking
Stribild experienced lower rates of neuropsychiatric side effects (Grades 1-4)
through 96 weeks compared to Atripla patients, including abnormal dreams (15
percent for Stribild vs. 28 percent for Atripla), dizziness (8 percent vs. 25
percent) and insomnia (11 percent vs. 16 percent). Patients taking Stribild
also experienced lower increases in total cholesterol and LDL (low-density
lipoprotein or “bad” cholesterol) compared to Atripla, and in Study 103,
experienced significantly smaller increases in triglycerides compared to those
taking the atazanavir-based regimen. Additionally, through week 96, reports of
Grade 3-4 hyperbilirubinemia were lower in the Stribild arm compared to the
atazanavir-based arm (0.6 percent vs. 65 percent).
In September 2012, Stribild was added to U.S. Department of Health and Human
Services (DHHS) guidelines as an “alternative” treatment regimen for patients
new to HIV therapy. Atripla and ritonavir-boosted atazanavir plus Truvada are
both listed as “preferred” first-line regimens in the guidelines. Stribild
has a Boxed Warning of lactic acidosis/severe hepatomegaly with steatosis and
post treatment acute exacerbation of hepatitis B; see below for important
Gilead recently initiated WAVES, a Phase 3b study evaluating Stribild compared
to ritonavir-boosted atazanavir plus Truvada ^ among more than 500
HIV-positive treatment-naïve women. Additional studies examining the efficacy
and safety of switching treatment-experienced virologically suppressed
patients to Stribild are also underway.
Study 102 is a randomized (1:1), double-blind Phase 3 clinical trial comparing
the efficacy, safety and tolerability of Stribild (elvitegravir 150
mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300
mg) (n=348) versus Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg) (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 <
50 copies/mL at 48 weeks of treatment, per the FDA snapshot algorithm.
Secondary objectives will 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. Across both arms, 33 percent of patients had HIV RNA > 100,000
copies/mL, and 13 percent of patients had CD4 counts ≤ 200 cells/mm^3.
At 96 weeks, mean increases in CD4 cell counts were 295 cells/mm^3 for
Stribild patients and 273 cells/mm^3 for Atripla patients (p=0.19). Virologic
failure rates were 6 percent for Stribild compared to 8 percent for Atripla.
Five percent of Stribild patients and 7 percent of Atripla patients
discontinued treatment due to adverse events. The most common adverse events
leading to treatment discontinuation among patients taking Stribild were renal
events, depression and fatigue. Between 48 and 96 weeks of treatment, two
Stribild patients discontinued due to serum creatinine increase without
features of proximal renal tubulopathy, and both patients improved after
Median changes from baseline in total cholesterol, HDL (high-density
lipoprotein or “good” cholesterol) and LDL at 96 weeks were, respectively, +9,
+6 and +9 mg/dL for Stribild and +18, +8 and +16 mg/dL for Atripla (total
cholesterol, p<0.001; HDL, p=0.008; LDL, p=0.011). The median change in
triglycerides was +4 mg/dL for Stribild and +8 mg/dL for Atripla (p=0.41).
Study 103 is a randomized (1:1), double-blind Phase 3 clinical trial comparing
the efficacy, safety and tolerability of Stribild (elvitegravir 150
mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300
mg) (n=353) versus atazanavir 300 mg boosted by ritonavir 100 mg plus Truvada
(emtricitabine and tenofovir disoproxil fumarate) (n=355) among HIV-infected
treatment-naïve adults with baseline HIV RNA levels > 5,000 copies/mL. The
primary endpoint of the study is the proportion of patients achieving HIV RNA
levels < 50 copies/mL at 48 weeks of treatment, per the FDA snapshot
algorithm. Secondary objectives will 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 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. Across both arms, 41 percent of patients had
HIV RNA > 100,000 copies/mL and 13 percent had CD4 counts ≤ to 200 cells/mm^3.
At 96 weeks, patients in both arms experienced similar increases in CD4 cell
counts (mean increase of 256 cells/mm^3 for Stribild and 261 cells/ mm^3 for
the atazanavir-based regimen). The virologic failure rate was 7 percent for
both treatment regimens. Five percent of Stribild patients and 6 percent of
patients on the atazanavir-based regimen discontinued treatment due to adverse
events. The most common adverse events leading to treatment discontinuation
among patients taking Stribild were renal events, diarrhea, pyrexia, nausea,
vomiting and fatigue. Between 48 and 96 weeks of treatment, one Stribild
patient and one patient in the atazanavir-based regimen discontinued due to
serum creatinine increase without features of proximal renal tubulopathy, and
both patients improved after treatment discontinuation.
Ocular icterus (associated with elevated bilirubin levels) was less common
among Stribild patients (less than 1 percent) compared to patients taking the
atazanavir-based regimen (14 percent).
Median changes from baseline in total cholesterol, HDL and LDL at 96 weeks,
were, respectively, +14, +6 and +14 mg/dL for Stribild, and +8, +5 and +11
mg/dL for the atazanavir-based regimen (total cholesterol, p=0.046; HDL,
p=0.24; LDL, p=0.32). The median change in triglycerides was +5 mg/dL for
Stribild and +16 mg/dL for the atazanavir-based regimen (p=0.012).
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, at which point all subjects will be given the option to
participate in an open-label rollover extension and receive Stribild.
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. A Marketing Authorisation Application
(MAA) for the regimen was validated for review by the European Medicines
Agency (EMA) on December 20, 2011. 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. Gilead submitted a New Drug
Application (NDA) to FDA for elvitegravir as a standalone agent on June 27,
2012, and the agency has set a target action date under the Prescription Drug
User Fee Act (PDUFA) of April 27, 2013. An MAA for elvitegravir in the EU was
validated for review by EMA on June 18, 2012.
Cobicistat is Gilead’s proprietary potent mechanism-based inhibitor of
cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body.
Unlike ritonavir, cobicistat acts only as a pharmacoenhancing or “boosting”
agent and has no antiviral activity. Gilead submitted an NDA to FDA for
cobicistat as a standalone agent on June 28, 2012, and a PDUFA date of April
28, 2013 has been set. An MAA for cobicistat in the EU was validated for
review by EMA on May 22, 2012.
Elvitegravir and cobicistat as standalone agents are investigational products
and their safety and efficacy have not yet been established.
Important Safety Information about Stribild
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 Emtriva or Viread,
which are 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 a loss of virologic response 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.
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 greater than 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 nephrotoxic agent.
*Use with 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 greater than
or equal to 5%; all grades) were nausea (16%), diarrhea (12%), abnormal
dreams (9%), headache (7%), and fatigue (5%)
*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
*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
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 starting patients new to therapy
on Stribild. 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
the European Medicines Agency may not approve marketing applications for
Stribild, elvitegravir and/or cobicistat in the timelines anticipated or at
all. 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
September 30, 2012, 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 is available at
U.S. full prescribing information for Atripla is available at www.Atripla.com.
U.S. full prescribing information for Truvada is available at www.Truvada.com.
EU Summary of Product Characteristics for Atripla and Truvada is available at
Stribild is a trademark of Gilead Sciences, Inc.
Truvada is a registered trademark 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, Investors, 650-522-1936
Cara Miller, Media (U.S.), 650-522-1616
Stephen Head, Media (Europe), +44 208-587-2359
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