Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has
submitted a Marketing Authorization Application (MAA) to the European
Medicines Agency (EMA) for marketing approval for the fixed-dose
combination of Truvada (emtricitabine and tenofovir
disoproxil (as fumarate)) and Tibotec Pharmaceuticals investigational
non-nucleoside reverse transcriptase inhibitor TMC278 (rilpivirine (as
hydrochloride)) for the treatment of HIV-1 infection in adults. Pending
approval, the new single-tablet regimen would be only the second product
that contains a complete antiretroviral treatment regimen in a single
once-daily tablet.
“The important role of complete, fixed-dose HIV treatment regimens is
well established in Europe”
The MAA will be reviewed by the Committee for Medicinal Products for
Human Use (CHMP). Review of the MAA will be conducted by the EMA under
the centralized licensing procedure, which, when finalized, provides one
marketing authorization in all 27 member states of the European Union.
An MAA for TMC278 also is being submitted today by Tibotec to the EMA
for review.
The important role of complete, fixed-dose HIV treatment regimens is
well established in Europe, said John C. Martin, PhD, Chairman and
Chief Executive Officer, Gilead Sciences. Today, nearly one quarter of
HIV patients in the major European countries are taking a one pill,
once-daily regimen, and recent updates to the International AIDS Society
guidelines support the use of these simplified regimens. We are pleased
to work with Tibotec in contributing another potentially important new
once-daily, fixed-dose treatment option.
The regulatory application for the fixed-dose combination is supported
by 48-week data from two Phase III double-blind, randomized studies
(ECHO and THRIVE) evaluating the safety and efficacy of TMC278 in
treatment-naive HIV-1 infected adults and a bioequivalence study
conducted by Gilead, which demonstrated that the formulation of the
fixed-dose combination of Truvada and TMC278 achieved the same levels of
medication in the blood as the component products dosed simultaneously.
ECHO (Efficacy Comparison
in treatment-naive HIV-infected
subjects Of TMC278 and Efavirenz)
evaluated TMC278 (25 mg) combined with a fixed-dose background regimen
consisting of emtricitabine (200 mg) and tenofovir disoproxil fumarate
(245 mg). THRIVE (TMC278 against HIV,
in a once-daily RegImen
Versus Efavirenz),
evaluated once-daily TMC278 (25 mg) compared to once-daily efavirenz
(600 mg) combined with an investigator-selected background regimen
consisting of two nucleoside reverse transcriptase inhibitors (abacavir
and lamivudine, or emtricitabine and tenofovir disoproxil fumarate, or
zidovudine and lamivudine).
Gilead entered into a license and collaboration agreement with Tibotec
Pharmaceuticals for the development and commercialization of a
single-tablet regimen containing TMC278 and emtricitabine and tenofovir
disoproxil fumarate for the treatment of HIV in July 2009. In April
2010, Gilead announced that it had successfully formulated and obtained
data supporting bioequivalence of the fixed-dose combination.
About TMC278 and the Fixed-Dose
Combination
TMC278 (rilpivirine (as hydrochloride)) is an investigational
non-nucleoside reverse transcriptase inhibitor being developed by
Tibotec Pharmaceuticals. Tibotec submitted a New Drug Application for
U.S. marketing approval of TMC278 on July 23, 2010 for once-daily use
with other antiretroviral agents in treatment-naive HIV-infected adults.
The investigational once-daily single-tablet regimen of Truvada/TMC278
contains 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (as
fumarate), both nucleoside reverse transcriptase inhibitors, and 25 mg
of rilpivirine (as hydrochloride), a non-nucleoside reverse
transcriptase inhibitor.
The fixed-dose single-tablet combination of Truvada/TMC278 is an
investigational product and the safety and efficacy have not yet been
established.
Additional Important Information About
Truvada
Truvada is a fixed-dose combination tablet containing 200 mg of
emtricitabine (Emtriva) and 245 mg of tenofovir disoproxil
(as fumarate) (Viread). In the European Union, Truvada is
indicated in combination with other antiretroviral agents (such as
non-nucleoside reverse transcriptase inhibitors or protease inhibitors)
for the treatment of HIV-1 infection in adults.
Truvada should not be administered concomitantly with other medicinal
products containing emtricitabine, tenofovir disoproxil (as fumarate) or
other cytidine analogs such as lamivudine and zalcitabine. Truvada
should not be administered with a third nucleoside analogue.
Emtricitabine and tenofovir are principally eliminated by the kidneys.
Renal impairment, including cases of acute renal failure and Fanconi
syndrome (renal tubular injury with severe hypophosphatemia), has been
reported in association with the use of Viread. It is recommended that
creatinine clearance be calculated in all patients prior to initiating
therapy with Truvada and renal function monitored every 4 weeks for the
first year and every three months thereafter.
In patients at risk of renal impairment, consideration should be given
to more frequent monitoring of renal function.
Dosing interval adjustment and close monitoring of renal function are
recommended in all patients with creatinine clearance 30-49 ml/min.
Truvada should be avoided with concurrent or recent use of a nephrotoxic
agent.
Coadministration of Truvada and didanosine is not recommended.
Co-administration of tenofovir disoproxil fumarate and didanosine
results in a 40-60 percent increase in systemic exposure to didanosine
that may increase the risk of didanosine-related adverse reactions. Rare
cases of pancreatitis and lactic acidosis, sometimes fatal, have been
reported. Patients on atazanavir/ritonavir and lopinavir/ritonavir plus
Truvada should be monitored for tenofovir-associated adverse events and
Truvada should be discontinued if these occur.
Decreases in bone mineral density (BMD) at the lumbar spine and hip have
been seen with the use of Viread. The effect on long-term bone health
and future fracture risk is unknown. If bone abnormalities are suspected
then appropriate consultation should be obtained. Cases of osteomalacia
(associated with proximal renal tubulopathy and which may contribute to
fractures) have been reported in association with the use of Viread.
Changes in body fat have been observed in patients taking anti-HIV
medicines. Immune Reconstitution Syndrome has been reported in patients
treated with combination therapy, including Viread and Emtriva, and may
necessitate further evaluation and treatment.
Most common adverse reactions (incidence greater-than or equal to 10
percent) are hypophosphatemia, dizziness, headache, diarrhea, nausea,
vomiting, elevated creatine kinase, asthenia and rash.
The parent compound of Viread was discovered through a collaborative
research effort between Dr. Antonin Holy, Institute for Organic
Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
(IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical
Research, Katholic University in Leuven, Belgium. The inventors of
Viread have agreed to waive their right to a royalty on sales of Viread
and Truvada in Gilead Access Program countries to ensure the product can
be offered at a no-profit price in parts of the world where the HIV/AIDS
epidemic has hit the hardest.
For complete prescribing information for Truvada, visit the EMA website.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops
and commercializes innovative therapeutics in areas of unmet medical
need. The companys 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 Australia.
Forward-Looking Statement
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, which
are subject to risks, uncertainties and other factors, including risks
related to Gileads ability to successfully commercialize the fixed-dose
combination of Truvada/TMC278. The EMA, FDA or other regulatory agencies
may not approve TMC278 or the fixed-dose combination of Truvada/TMC278
for the treatment of HIV-infection in treatment-nave adults, and any
marketing approval, if granted, may have significant limitations on its
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 Gileads Quarterly Report on Form 10-Q for the first and
second quarters of 2010, 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 Truvada is available at www.Truvada.com.
U.S.
full prescribing information for Viread is available at www.Viread.com.
U.S.
full prescribing information for Emtriva is available at www.GileadHIV.com.
EU Summary of Product Characteristics for Truvada, Viread and Emtriva
are available at http://www.ema.europa.eu/ema/index.jsp?curl=/pages/home/Home_Page.jsp
Truvada, Viread and Emtriva are registered trademarks of Gilead
Sciences, Inc.
For more information on Gilead Sciences, please visit the companys
website at www.gilead.com
or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000
Source: Business Wire
