Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has
dosed the first patient in the Phase III clinical program
evaluating its investigational fixed-dose, single-tablet “Quad”
regimen of elvitegravir, cobicistat (formerly GS 9350),
emtricitabine and tenofovir disoproxil fumarate. The Phase III
clinical program for the Quad includes two studies (Studies 102 and
103) that will evaluate the Quad regimen versus a standard of care
among HIV-1 infected antiretroviral treatment-naïve adults.
“We are pleased to announce that the Quad Phase III clinical
program is underway,” said Norbert Bischofberger, PhD, Executive
Vice President, Research and Development and Chief Scientific
Officer, Gilead Sciences. “Efficacy and safety results from the
Phase II study suggest that the Quad may represent an important new
option for patients with HIV. We look forward to further defining
the clinical profile of the Quad in a larger number of patients in
the Phase III trials.”
Gilead is also examining cobicistat as a stand-alone boosting
agent for other antiretrovirals, in particular protease inhibitors.
Later this quarter, Gilead plans to initiate a Phase III clinical
trial evaluating the efficacy, safety and tolerability of
cobicistat-boosted atazanavir compared to ritonavir-boosted
atazanavir, each in combination with Truvada® (emtricitabine and
tenofovir disoproxil fumarate).
Study Design
Study 102 is a randomized, double-blind clinical trial that will
compare the efficacy, safety and tolerability of the Quad versus
Atripla® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg) over a 96-week period at 130 study
sites in the United States and Puerto Rico. Eligible participants
will be HIV-infected treatment-naïve adults with HIV RNA levels
greater than or equal to 5,000 copies/mL. Approximately 700 trial
participants will be randomized (1:1) to receive a once-daily
tablet containing elvitegravir 150 mg/cobicistat 150
mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg
(n=350) or Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg) (n=350).
Study 103 is a randomized, double-blind clinical trial that will
compare the efficacy, safety and tolerability of the Quad versus
ritonavir-boosted atazanavir and Truvada over a 96-week period at
more than 200 study sites in North America, South America, Europe
and Asia Pacific. Eligible participants will be HIV-infected
treatment-naïve adults with HIV RNA levels greater than or equal to
5,000 copies/mL. Approximately 700 trial participants will be
randomized (1:1) to receive a once-daily tablet containing
elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200
mg/tenofovir disoproxil fumarate 300 mg (n=350) or ritonavir 100 mg
and atazanavir 300 mg and emtricitabine 200 mg/tenofovir disoproxil
fumarate 300 mg (n=350).
The primary endpoint of both trials will be the proportion of
patients achieving HIV RNA levels of less than 50 copies/mL at 48
weeks of treatment. Secondary objectives will evaluate the
efficacy, safety and tolerability of the treatment regimens through
96 weeks of treatment.
After week 96, subjects 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 the Quad single-tablet
regimen.
About
Elvitegravir
Elvitegravir is an HIV integrase inhibitor. Unlike other classes
of antiretroviral agents, 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.
About
Cobicistat
Cobicistat is Gilead’s proprietary potent mechanism-based
inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes
drugs in the body. In addition to studying the agent as part of an
integrase-based fixed-dose regimen, Gilead is also examining
cobicistat’s potential stand-alone role in boosting commercially
available HIV protease inhibitors, which are used in many HIV
treatment regimens.
The fixed-dose single-tablet “Quad” regimen, elvitegravir and
cobicistat are investigational products and have not yet been
determined safe or efficacious in humans.
Important Product Safety
Information About Truvada and Atripla
Lactic acidosis and severe hepatomegaly with steatosis,
including fatal cases, have been reported with the use of
nucleoside analogues alone or in combination with other
antiretrovirals including Viread (tenofovir disoproxil fumarate), a
component of Atripla and Truvada. Atripla and Truvada are not
approved for the treatment of chronic hepatitis B virus (HBV)
infection and their safety and efficacy have not been established
in patients co-infected with HBV and HIV-1. Severe acute
exacerbations of hepatitis B have been reported in patients
co-infected with HIV-1 and HBV who have discontinued Atripla or
Truvada. Hepatic function should be monitored closely with
both clinical and laboratory follow-up for at least several months
in patients who are co-infected with HBV and HIV-1 and discontinue
Atripla or Truvada. If appropriate, initiation of anti-hepatitis B
treatment may be warranted.
It is important for patients to be aware that anti-HIV medicines
including Atripla and Truvada do not cure HIV infection or
AIDS and do not reduce the risk of transmitting HIV to others.
Additional Important
Information About Truvada
Truvada is a fixed-dose combination tablet containing 200 mg of
emtricitabine (Emtriva) and 300 mg of tenofovir disoproxil fumarate
(Viread). In the United States, 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 coadministered with Atripla, Emtriva,
Viread or lamivudine-containing products, including Combivir®
(lamivudine/zidovudine), Epivir® or Epivir-HBV® (lamivudine),
Epzicom® (abacavir sulfate/lamivudine) or Trizivir® (abacavir
sulfate/lamivudine/zidovudine). In treatment-experienced patients,
the use of Truvada should be guided by laboratory testing and
treatment history.
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 as
clinically appropriate during therapy. Routine monitoring of
calculated creatinine clearance and serum phosphorous should be
performed in patients at risk for renal impairment including
patients who have previously experienced renal events while
receiving Hepsera® (adefovir dipivoxil). 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.
Truvada should not be administered with Hepsera.
Coadministration of Truvada and didanosine should be undertaken
with caution. Patients should be monitored closely for
didanosine-associated adverse events and didanosine should be
discontinued if these occur. Dose reduction of didanosine should be
considered, if warranted. Patients on atazanavir and
lopinavir/ritonavir plus Truvada should be monitored for
Truvada-associated adverse events and Truvada should be
discontinued if these occur. When co-administered with Truvada, it
is recommended that atazanavir be boosted with ritonavir 100 mg.
Atazanavir without ritonavir should not be co-administered with
Truvada.
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. BMD monitoring
should be considered in patients with a history of pathologic
fractures or who are at risk for osteopenia. 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 ≥10 percent) are
diarrhea, nausea, fatigue, headache, dizziness, depression,
insomnia, abnormal dreams, 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 the Gilead Access
Program countries to ensure the product can be offered at a
no-profit price in parts of the world where the epidemic has hit
the hardest.
For complete prescribing information for Truvada, visit
www.Truvada.com.
Additional Important
Information About Atripla
In the United States, Atripla is indicated for use alone as a
complete regimen or in combination with other antiretroviral agents
for the treatment of HIV-1 infection in adults.
Atripla contains the components of Truvada (emtricitabine and
tenofovir disoproxil fumarate) and Sustiva (efavirenz),
co-formulated as a single tablet. As such, the important safety
information appearing in the above Truvada section also applies to
Atripla, in addition to the following important product
information.
As a fixed-dose regimen of Viread (tenofovir disoproxil
fumarate), Emtriva (emtricitabine) and Sustiva (efavirenz), Atripla
should not be coadministered with Viread, Emtriva, Truvada
(emtricitabine and tenofovir disoproxil fumarate) or Sustiva. Due
to similarities between Emtriva and lamivudine, Atripla should not
be coadministered with drugs containing lamivudine, including
Combivir® (lamivudine/zidovudine), Epivir® or Epivir-HBV®
(lamivudine), Epzicom® (abacavir sulfate/lamivudine) or Trizivir®
(abacavir sulfate/lamivudine/zidovudine).
Atripla should not be taken with bepridil, cisapride, midazolam,
pimozide, triazolam, or ergot derivatives due to a contraindication
with efavirenz. Use of Atripla with voriconazole, St. John's wort
(Hypericum perforatum) or St. John's wort-containing products is
not recommended. Use of Atripla with atazanavir or
atazanavir/ritonavir is not recommended.
Atripla should not be given to patients with creatinine
clearance less than 50 ml/min.
Serious psychiatric adverse experiences, including severe
depression (2.4 percent), suicidal ideation (0.7 percent), nonfatal
suicide attempts (0.5 percent), aggressive behavior (0.4 percent),
paranoid reactions (0.4 percent) and manic reactions (0.2 percent)
have been reported in patients treated with efavirenz, a component
of Atripla. In addition to efavirenz, factors identified in a
clinical study that were associated with an increase in psychiatric
symptoms included a history of injection drug use, psychiatric
history and use of psychiatric medication. There have been
occasional reports of death by suicide, delusions, and
psychosis-like behavior, but it could not be determined if
efavirenz was the cause. Patients with serious psychiatric adverse
experiences should be evaluated immediately to determine whether
the risks of continued therapy outweigh the benefits. Patients
should tell their doctor if they have a history of mental illness
or are using drugs or alcohol.
Fifty-three percent of patients in clinical studies have
reported central nervous system symptoms including dizziness (28.1
percent), insomnia (16.3 percent), impaired concentration (8.3
percent), somnolence (7.0 percent), abnormal dreams (6.2 percent)
and hallucinations (1.2 percent) when taking efavirenz compared to
25 percent of patients receiving control regimens. These symptoms
usually begin during the first or second day of therapy and
generally resolve after the first two to four weeks of therapy.
After four weeks of therapy, the prevalence of central nervous
system symptoms of at least moderate severity ranged from 5 to 9
percent in patients treated with regimens containing efavirenz.
Nervous system symptoms are not predictive of the less frequent
psychiatric symptoms.
Women should not become pregnant or breastfeed while taking
Atripla. Serious birth defects have been seen in children of women
treated with efavirenz during pregnancy. Women must use a reliable
form of barrier contraception, such as a condom, for 12 weeks after
discontinuation of Atripla even if they also use other methods of
birth control.
Rash is a common side effect that usually goes away without any
change in treatment. Rash may be a serious problem in some
patients.
In patients with known or suspected history of hepatitis B or C
and in patients treated with other medications associated with
liver toxicity, monitoring of liver enzymes is recommended.
Atripla should be used with caution in patients with a history
of seizures. Convulsions have been observed in patients receiving
efavirenz, generally in the presence of a known medical history of
seizures.
Invirase® (saquinavir) should not be used as the only protease
inhibitor in combination with Atripla.
The most significant adverse events observed in patients treated
with Sustiva are nervous system symptoms, psychiatric symptoms and
rash. The most common adverse events (at least 5 percent) observed
in clinical studies with Sustiva include fatigue, pain, dizziness,
headache, insomnia, impaired concentration, nausea, vomiting,
diarrhea, depression, rash and pruritus.
For complete prescribing information for Atripla, visit
www.Atripla.com.
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 Australia.
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 Gilead’s ability to complete enrollment
of the Phase III clinical trials for the Quad and to initiate the
Phase III clinical trial of cobicistat in the timeline currently
anticipated. In addition, we may face challenges in clinical trial
protocol design, there may be unfavorable results of the ongoing or
any further clinical trials of the Quad or cobicistat, and Gilead
may need to modify or delay such clinical trials. Gilead may
ultimately be unable to obtain the U.S. Food and Drug
Administration and other regulatory body approvals, and as a
result, the Quad or cobicistat may never be successfully
commercialized. Further, Gilead may make a strategic decision to
discontinue development of the Quad or cobicistat if, for example,
it believes commercialization will be difficult relative to other
opportunities in its pipeline. 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. Gilead
directs readers to its Annual Report on Form 10-K for the year
ended December 31, 2009. Gilead claims the protection of the Safe
Harbor contained in the Private Securities Litigation Reform Act of
1995 for forward-looking statements. 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
Atripla is available at www.Atripla.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.
U.S. full prescribing information for
Hepsera is available at www.Hepsera.com.
Truvada, Viread, Emtriva and Hepsera
are registered trademarks of Gilead Sciences, Inc.
Atripla is a registered trademark of
Bristol-Myers Squibb & Gilead Sciences, LLC.
For more information on Gilead
Sciences, please visit the company's website at www.gilead.com or
call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Gilead Sciences (NASDAQ:GILD)
Historical Stock Chart
From Jun 2024 to Jul 2024
Gilead Sciences (NASDAQ:GILD)
Historical Stock Chart
From Jul 2023 to Jul 2024