Gilead Initiates Phase 3 Clinical Program for Tenofovir Alafenamide, a Novel Low-Dose Prodrug for the Treatment of HIV

  Gilead Initiates Phase 3 Clinical Program for Tenofovir Alafenamide, a Novel
  Low-Dose Prodrug for the Treatment of HIV

   -- Two Studies Will Compare a Tenofovir Alafenamide-Based Single Tablet
                      Regimen to Gilead’s Stribild^® --

Business Wire

FOSTER CITY, Calif. -- January 24, 2013

Gilead Sciences, Inc. (Nasdaq: GILD) today announced the initiation of the
first of two Phase 3 clinical trials (Study 104) evaluating a single tablet
regimen containing tenofovir alafenamide (TAF) for the treatment of HIV-1
infection in treatment-naïve adults. TAF is a novel prodrug of tenofovir, the
active agent in Viread^® (tenofovir disoproxil fumarate). The Phase 3 studies
will examine a once-daily single tablet regimen of TAF 10 mg/elvitegravir 150
mg/cobicistat 150 mg/emtricitabine 200 mg compared to Gilead’s Stribild^®
(elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg) among patients new to HIV therapy. The second
Phase 3 study (Study 111) will be initiated later this quarter.

“We are pleased to move TAF into Phase 3 clinical research,” said Norbert
Bischofberger, PhD, Executive Vice President, Research and Development and
Chief Scientific Officer, Gilead Sciences. “We believe that TAF’s smaller
milligram size has the potential to offer safety and tolerability advantages
over existing therapies, and may enable the creation of new single tablet
regimens for HIV.”

In October 2012, Gilead announced topline results from a Phase 2 study
comparing the TAF/elvitegravir/cobicistat/emtricitabine single tablet regimen
to Stribild. The study found that the TAF-based regimen met its primary
objective based on the proportion of patients with HIV RNA (viral load) levels
< 50 copies/mL at 24 weeks of therapy. In addition, statistically significant
differences in bone and renal safety were observed between the two arms in
favor of the TAF-containing regimen. Both the type and frequency of laboratory
abnormalities and adverse events were otherwise comparable between study arms.
Full results from the Phase 2 study will be presented at an upcoming medical

Stribild was approved by the U.S. Food and Drug Administration (FDA) in August
2012 and is Gilead’s third single tablet regimen for HIV. A marketing
application for Stribild is currently pending in Europe.

About the TAF Phase 3 Studies

Study 104 and Study 111 are randomized, double-blind, 96-week clinical trials
among treatment-naïve HIV-1 infected adults with viral load greater than or
equal to 1,000 copies/mL. In each study, a total of 840 patients will be
randomized (1:1) to receive a once-daily tablet containing TAF 10
mg/elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg (n=420) or
Stribild (n=420).

The primary endpoint of the studies will be the proportion of patients with
viral load < 50 copies/mL at 48 weeks of treatment as determined by the
FDA-defined snapshot analysis. Secondary endpoints will include the proportion
of patients with viral load < 20 copies/mL and < 200 copies/mL at 48 and 96
weeks of therapy as defined by the FDA snapshot analysis, the proportion of
patients with viral load < 50 copies/mL at week 48 as defined by the FDA Time
to Loss of Virologic Response (TLOVR) analysis, the proportion of patients
with viral load < 50 copies/mL at week 96 as defined by the FDA snapshot and
TLOVR analyses, and change from baseline in CD4+ cell count at weeks 48 and

The studies will include patients with impaired renal function, i.e., those
patients with an estimated glomerular filtration rate between 50 mL/mn and 90
mL/mn (according to the Cockcroft-Gault formula). Bone mineral density will be
assessed for all patients by DEXA scans at baseline and every 24 weeks. After
week 96, patients will continue to take their blinded study drug until
treatment assignments have been unblinded, at which point all will be given
the option to participate in an open-label rollover extension and receive the
TAF-based single tablet regimen.

About Tenofovir Alafenamide

Tenofovir alafenamide (TAF) is a nucleotide reverse transcriptase inhibitor
(NtRTI). It is a novel prodrug of tenofovir, the active agent in Viread^®
(tenofovir disoproxil fumarate), which is also an NtRTI. Phase 1b dose-ranging
studies identified a dose of TAF that is ten times lower than Viread and
provides greater antiviral efficacy. The smaller milligram size of TAF may
enable the development of new fixed-dose combinations and single tablet
regimens for HIV therapy that are not feasible with Viread.

About Elvitegravir

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.

About Cobicistat

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.

TAF-containing regimens and TAF, elvitegravir and cobicistat as single agents
are investigational products and their safety and efficacy have not yet been

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.

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 risks related to our ability
to enroll patients in the clinical trials involving TAF and the possibility of
unfavorable results from these clinical trials. In addition, Gilead may make a
strategic decision to discontinue development of TAF if, for example, Gilead
believes commercialization will be difficult relative to other opportunities
in its pipeline. There is also risk that Gilead may not be able to commence
the second clinical trial of TAF and file for regulatory approval of TAF in
the anticipated timelines. Further, Gilead may be unable to obtain approvals
from regulatory authorities for TAF, elvitegravir and/or cobicistat, alone or
in combination with other products. If marketing approval is granted for any
of these products, there may be significant limitations on their use. As a
result, these product candidates as standalone agents or as part of single
tablet regimens may never be successfully commercialized. 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 statements.

    U.S. full prescribing information for Emtriva, Stribild and Viread is
                         available at

  Emtriva, Stribild and Viread are registered trademarks of Gilead Sciences,

For more information on Gilead Sciences, please visit the company’s website at, 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)
Erin Rau, 650-522-5635 (Media)
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