January 24, 2013
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® --
“We are pleased to move TAF into Phase 3 clinical research,” said
Stribild was approved by the
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 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.
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
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
TAF-containing regimens and TAF, elvitegravir and cobicistat as single agents are investigational products and their safety and efficacy have not yet been established.
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
U.S. full prescribing information for Emtriva, Stribild and Viread is available at www.gilead.com.
Emtriva, Stribild and Viread are registered trademarks of
For more information on
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Erin Rau, 650-522-5635 (Media)