– E/C/F/TAF Regimen Demonstrates Statistical
Superiority with Significant Improvements in Bone and Renal
Laboratory Parameters Compared to TDF-based Regimens –
Gilead Sciences, Inc. (NASDAQ:GILD) today announced detailed
48-week data from an open-label Phase 3 study (Study 109)
evaluating its investigational once-daily single tablet regimen
(STR) of elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200
mg and tenofovir alafenamide 10 mg (E/C/F/TAF) among 1,436
virologically suppressed adult patients switching from tenofovir
disoproxil fumarate (TDF)-containing regimens. The study met its
primary endpoint by demonstrating non-inferiority of E/C/F/TAF to
the TDF-based regimens at Week 48. The study also demonstrated
statistical superiority among patients with HIV-1 RNA levels less
than 50 copies/mL at Week 48 and statistically significant
improvements in bone and renal laboratory parameters. These data
were presented in an oral session (session TUAB0102) at the 8th IAS
Conference on HIV Pathogenesis, Treatment & Prevention (IAS) in
Vancouver, Canada.
In November 2014, Gilead filed a New Drug Application (NDA) with
the U.S. Food and Drug Administration (FDA) for E/C/F/TAF, the
first investigational once-daily TAF-based STR. TAF is an
investigational novel nucleotide reverse transcriptase inhibitor
(NRTI) that has demonstrated high antiviral efficacy at a dose less
than one-tenth that of Gilead’s Viread® (TDF), as well as
improved renal and bone laboratory parameters as compared to TDF in
earlier clinical trials in combination with other antiretroviral
agents.
“The results of this study demonstrate that E/C/F/TAF has the
potential to offer clear advantages for patients with HIV over
existing TDF-based therapies,” said Tony Mills, MD, lead author of
the Phase 3 study, Medical Director, Southern California Men’s
Medical Group, and Assistant Professor of Clinical Medicine,
University of California, Los Angeles. “This is the first large
study to demonstrate that switching from a TDF-based regimen to
E/C/F/TAF can help improve patients’ bone and kidney measures.”
In the open-label study, virologically suppressed adults with
normal renal function taking one of four different TDF-based
regimens for at least 96 weeks were randomized 2:1 to receive
E/C/F/TAF or to maintain their TDF-based regimen. The four
TDF-based treatments evaluated in the study included the following
single tablet and multi-pill regimens:
elvitegravir/cobicistat/emtricitabine/TDF (Stribild®);
efavirenz/emtricitabine/TDF (Atripla®); atazanavir/ritonavir +
emtricitabine/TDF (Truvada®) or atazanavir/cobicistat +
Truvada.
Among the 1,436 patients who were randomized in the study
(E/C/F/TAF, 959 patients; TDF-based regimen, 477 patients),
virologic success rates at Week 48 were higher in patients taking
E/C/F/TAF (97 percent versus 93 percent for all TDF-based regimens;
difference in percentages: 4.1 percent, 95 percent CI: 1.6 percent
to 6.7 percent). The rates of virologic failure were similar
between the two arms (E/C/F/TAF, 1.0 percent; TDF-based regimen,
1.3 percent). General safety was similar between the two arms
through 48 weeks of treatment, with similar percentages of patients
in each group having any adverse events. Adverse events leading to
treatment discontinuation were more common among patients treated
with a TDF-based regimen (E/C/F/TAF, 0.9 percent; TDF-based
regimen, 2.5 percent). The most commonly reported adverse events
included upper respiratory tract infection, diarrhea,
nasopharyngitis and headache.
Statistically significant improvements from baseline to Week 48
in mean bone mineral density (BMD) at the hip and spine were
observed in patients in the E/C/F/TAF group as compared to patients
in the TDF-based regimen group (hip: E/C/F/TAF, 1.37 percent;
TDF-based regimen, -0.26 percent; spine: E/C/F/TAF, 1.79 percent;
TDF-based regimen, -0.28 percent (p<0.001 for the differences
between groups at Week 48)).
Significant improvements in multiple tests of renal function
also were observed among patients treated with E/C/F/TAF compared
with TDF-based regimens. At Week 48, patients who switched to
E/C/F/TAF had a median percentage change from baseline in urine
protein-to-creatinine ratio (UPCR) (-21 percent vs. +10 percent;
p<0.001); urine albumin-to-creatinine ratio (UACR) (-18 percent
vs. +9 percent; p<0.001); urine retinol binding
protein-to-creatinine ratio (-33 percent vs. +18 percent;
p<0.001) and urine beta-2 microglobulin-to-creatinine ratio (-52
percent vs. +19 percent; p<0.001). There were no cases of
Fanconi Syndrome in the E/C/F/TAF arm and one case in the TDF-based
regimen arm.
In the same IAS oral session, researchers reported new 48-week
data from a separate trial that also found improvements in multiple
laboratory parameters of renal and bone safety among HIV-infected,
virologically suppressed adult patients who switched treatment
regimens to E/C/F/TAF from both TDF- and non-TDF containing
regimens (session TUAB0103). This open-label study (Study 112)
included 242 patients with mild-to-moderate renal impairment
(eGFRCG 30-69 mL/min), showing that from baseline to Week 48 the
prevalence of proteinuria (UPCR > 200 mg/g) and albuminuria
(UACR > 30 mg/g) decreased from 41 percent to 16 percent and
from 49 percent to 26 percent, respectively, among these patients
who switched to E/C/F/TAF. Significant increases in mean percent
change in hip (+1.47 percent) and spine (+2.29 percent) BMD were
also observed (p<0.001 for both). Patients taking non-TDF based
regimens pre-switch had no significant changes from baseline
measures of renal function or BMD.
“The data presented at IAS this week demonstrate the potential
of E/C/F/TAF to help address the long-term care of a range of
patients,” said Norbert Bischofberger, PhD, Executive Vice
President, Research and Development and Chief Scientific Officer,
Gilead Sciences. “Gilead has a long history of innovation in the
field of HIV, and E/C/F/TAF and the rest of the TAF-based portfolio
is poised to represent the next generation of safe, simple and
highly effective regimens.”
Gilead is presenting data from two other important trials at
IAS, including a Phase 3, 24-week study in HIV patients co-infected
with hepatitis B who switched from a multi-pill regimen to a single
tablet regimen of E/C/F/TAF and 48-week data from an international
trial examining the safety and efficacy of Stribild among
treatment-naïve women (Posters WELBPE13 and MOLBPE08,
respectively).
In addition to E/C/F/TAF, Gilead has filed NDAs with the FDA for
two other TAF-based HIV medicines: two doses of an investigational
fixed-dose combination of F/TAF (200/10 mg and 200/25 mg) for use
in combination with other HIV antiretroviral agents; and an
investigational, once-daily STR that combines Gilead’s
emtricitabine (200 mg) and TAF (25 mg) with rilpivirine (25 mg)
from Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical
Companies of Johnson & Johnson, (R/F/TAF), for the treatment of
adult and pediatric patients 12 years of age and older.
Under the Prescription Drug User Fee Act, the FDA has set a
target action date of November 5, 2015, for E/C/F/TAF and April 7,
2016, for F/TAF. Marketing Authorization Applications (MAA) in the
European Union were fully validated on December 23, 2014, and May
28, 2015, for E/C/F/TAF and F/TAF respectively. Gilead will submit
a MAA for R/F/TAF in the third quarter of 2015.
A fourth investigational TAF-based HIV treatment is under
development, containing Gilead’s TAF, emtricitabine and cobicistat,
with Janssen’s darunavir (D/C/F/TAF).
E/C/F/TAF and other TAF-based regimens are investigational
products and have not been determined to be safe or
efficacious.
About Study 109
Study 109 is a randomized, open-label, multi-national,
active-controlled study to evaluate the non-inferiority of
switching to a TAF-containing combination STR relative to
maintaining TDF-containing combination regimens in
virologically-suppressed HIV-1 positive adult subjects (HIV-1 RNA
<50 copies/mL at Week 48) following the switch. The study was
also designed to test for statistical superiority between the two
study arms once non-inferiority was achieved.
A total of 1,436 virologically suppressed patients with normal
renal function were randomized in the study. Demographic and
general baseline characteristics were similar between the two
treatment groups with the exception of ethnicity; a higher
proportion of patients in the E/C/F/TAF group (25.9 percent, 248
patients) compared with the TDF-based regimen group (17.2 percent,
82 patients) were of Hispanic or Latino ethnicity (p<0.001).
Most patients were male (89.3 percent), with a median age of 41
years (range: 21 to 77 years); most were either white (67.2
percent) or black (18.9 percent). Additional information about the
study can be found at www.clinicaltrials.gov.
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. Gilead has
operations in more than 30 countries worldwide, with headquarters
in Foster City, California.
Forward-Looking
Statement
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 that the FDA and other regulatory
authorities may not approve E/C/F/TAF, F/TAF, R/F/TAF, D/C/F/TAF
and other F/TAF-based regimens in the currently anticipated
timelines or at all, and marketing approvals, if granted, may have
significant limitations on their use. As a result, E/C/F/TAF,
F/TAF, R/F/TAF, D/C/F/TAF and other F/TAF-based regimens may never
be successfully commercialized. In addition, Gilead may be unable
to file for regulatory approval for these TAF-based regimens with
the FDA and other regulatory authorities in the currently
anticipated timelines. 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 Annual Report on Form 10-Q for
the quarter ended March 31, 2015, 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 statements.
U.S. full prescribing information for Viread,
Stribild, Atripla and Truvada, including BOXED WARNING, is
available at www.gilead.com.
Viread, Stribild and Truvada are registered
trademarks of Gilead Sciences, Inc., or its related companies.
ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead
Sciences, LLC.
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.
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version on businesswire.com: http://www.businesswire.com/news/home/20150721006425/en/
Gilead Sciences, Inc.Investors:Patrick O’Brien,
650-522-1936Media:Ryan McKeel, 650-377-3548
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