|[December 13, 2013]
U.S. FDA Approves Gilead's Once-Daily Single Tablet HIV-1 Regimen Complera® for Patients Switching from a Stable Regimen
FOSTER CITY, Calif. --(Business Wire)--
Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food
and Drug Administration (FDA) has approved the single tablet HIV-1
regimen Complera® (emtricitabine/rilpivirine/tenofovir
disoproxil fumarate) for use in certain virologically-suppressed (HIV
RNA <50 copies/mL) adult patients on a stable antiretroviral regimen in
order to replace their current antiretroviral treatment regimen.
Complera was first approved in 2011 for patients new to therapy and is
now one of the most widely-prescribed HIV regimens in the United States.
"Complera is an effective single-pill therapy with a demonstrated safety
profile, and has rapidly become an important option for appropriate HIV
patients who are initiating antiretroviral treatment," said Calvin J.
Cohen, MD, M.Sc., Research Director, Community Research Initiative of
New England and an investigator on clinical trials of Complera. "The
data supporting today's approval demonstrate Complera has the potential
to help a broader range of HIV-infected patients who have achieved
virologic control on another regimen."
Complera combines a complete course of three antiretroviral medications
into a single, once-daily tablet. The product contains Gilead's Truvada®,
which itself is a fixed-dose combination of two HIV medicines, and
Janssen R&D Ireland's rilpivirine (marketed as Edurant®).
Patients switching to Complera should have no history of virologic
failure, have suppressed viral load for at least six months, be on their
first or second antiretroviral regimen, and have no current or past
history of resistance to Complera components. The efficacy of Complera
was established in patients who were virologically suppressed (HIV RNA
<50 copies/mL) on a stable ritonavir-boosted protease
Today's approval is supported by clinical data from the Phase 3 SPIRIT
(Study 106) clinical trial. In this randomized, open-label study,
virologically suppressed patients who were taking multi-tablet HIV
therapy containing a ritonavir-boosted protease inhibitor (PI) either
switched to Complera or remained on their PI-based regimen. The study
found that, after 48 weeks of treatment with Complera, 89 percent
(n=283/317) of switch patients had viral load less than 50 copies/mL,
compared to 90 percent (143/159) of patients who remained on a
PI-regimen for 24 weeks. Complera was well tolerated in SPIRIT and there
were few treatment discontinuations due to adverse events. The most
common side effects in previous clinical studies of Complera were
headache, depressive disorders and insomnia (2 percent for all). No new
adverse reactions were identified in SPIRIT, but the frequency of
adverse reactions increased from 2 percent to 2.4 percent. Complera has
a labeled Boxed Warning on the risks of lactic acidosis/severe
hepatotoxicity with steatosis and acute exacerbation of hepatitis B; see
below for Important Safety Information.
Marketed as Eviplera® (emtricitabine/rilpivirine/tenofovir
disoproxil (as fumarate)) in the European Union, the regimen also was
recently granted European regulatory approval for any HIV-infected adult
patients without known mutations associated with resistance to the
non-nucleoside reverse transcriptase inhibitor (NNRTI) class, tenofovir
or emtricitabine, and with a viral load = 100,000 HIV-1 RNA copies/mL.
Important Safety Information about Complera
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and
POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
Lactic acidosis and severe hepatomegaly with steatosis, including
fatal cases, have been reported with the use of nucleoside analogs,
including tenofovir disoproxil fumarate (tenofovir DF), a component of
COMPLERA, in combination with other antiretrovirals.
COMPLERA is not approved for the treatment of chronic hepatitis B
virus (HBV) infection and the safety and efficacy of COMPLERA have not
been established in patients coinfected with HBV and HIV-1. Severe acute
exacerbations of hepatitis B have been reported in patients who are
coinfected with HBV and HIV-1 and have discontinued emtricitabine or
tenofovir DF, which are components of COMPLERA. Hepatic function should
be monitored closely with both clinical and laboratory follow-up for at
least several months in patients who are coinfected with HIV-1 and HBV
and discontinue COMPLERA. If appropriate, initiation of anti-hepatitis B
therapy may be warranted.
Coadministration: COMPLERA should not be coadministered with
drugs that induce CYP3A or increase gastric pH as this may lead to
loss of virologic response and possible resistance to COMPLERA. Use of
the following drugs with COMPLERA is contraindicated: carbamazepine,
oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin,
rifapentine, proton pump inhibitors (e.g., esomeprazole, lansoprazole,
dexlansoprazole, omeprazole, pantoprazole, rabeprazole), systemic
dexamethasone (>1 dose) and St. John's wort.
WARNINGS AND PRECAUTIONS
New onset or worsening renal impairment: Cases of acute renal
failure and Fanconi syndrome have been reported with the use of
tenofovir DF. In all patients, assess estimated creatinine clearance
(CrCl) prior to initiating and during therapy. In patients at risk for
renal dysfunction, additionally monitor serum phosphorus, urine
glucose, and urine protein. Do not administer COMPLERA in patients
with CrCl <50 mL/min. Avoid concurrent or recent use with a
nephrotoxic agent. Cases of acute renal failure, some requiring
hospitalization and renal replacement therapy, have been reported
after initiation of high dose or multiple NSAIDs in patients with risk
factors for renal dysfunction; consider alternatives to NSAIDs in
these patients. Persistent or worsening bone pain, pain in
extremities, fractures and/or muscular pain or weakness may be
manifestations of proximal renal tubulopathy and should prompt an
evaluation of renal function.
Drug interactions: Use COMPLERA with caution when given with
drugs that may reduce the exposure of rilpivirine or when
coadministered with a drug with known risk of Torsades de Pointes.
Supratherapeutic doses of rilpivirine have been shown to prolong the
QTc interval of the electrocardiogram (ECG) in healthy subjects.
Depressive disorders: The incidence of depressive disorders
(depressed mood, depression, dysphoria, major depression, mood
altered, negative thoughts, suicide attempt, suicidal ideation)
reported in clinical trials (N=686) was 9% (most were mild or moderate
in severity); and Grades 3 and 4 depressive disorders (regardless of
causality) was 1%. Suicidal ideation was reported in 4 subjects and
suicide attempt was reported in 2 subjects. Patients with severe
depressive symptoms should seek immediate medical evaluation and the
risks of continued therapy should be determined.
Hepatotoxicity: Hepatic adverse events have been
reported, including cases of hepatic toxicity in patients without
pre-existing hepatic disease or other identifiable risk factors.
Patients with underlying hepatitis B or C, or those with marked
elevations in liver-associated tests may be at increased risk.
Appropriate laboratory testing and monitoring before and during
therapy is recommended in patients with underlying hepatic disease or
in patients with marked elevations in liver-associated tests prior to
treatment initiation; consider testing and monitoring in patients
without pre-existing hepatic dysfunction or other risk factors.
Bone effects: Decreases in bone mineral density (BMD) and
mineralization defects, including osteomalacia, have been seen in
patients treated with tenofovir DF. Consider monitoring BMD in
patients with a history of pathologic fracture or risk factors for
bone loss. In patients at risk of renal dysfunction who present with
persistent or worsening bone or muscle symptoms, hypophosphatemia and
osteomalacia secondary to proximal renal tubulopathy should be
Other antiretrovirals: COMPLERA is a complete regimen for the
treatment of HIV-1 infection. Do not coadminister with other
antiretrovirals including products containing any of the same active
components, products containing lamivudine, or with adefovir dipivoxil.
Fat redistribution and accumulation has been observed in
patients receiving ARV therapy.
Immune reconstitution syndrome, including the occurrence of
autoimmune disorders with variable times to onset, has been reported.
In adults with no ARV treatment history: Common adverse
reactions reported in clinical studies (incidence =2%, Grades 2-4)
were depressive disorders (2%), insomnia (2%) and headache (2%).
In virologically suppressed adults: No new types of adverse
reactions to COMPLERA were identified in stable, virologically
suppressed patients switching to COMPLERA; however, the frequency of
adverse reactions increased by 20%.
CYP3A inducers: Drugs that induce CYP3A may decrease
rilpivirine plasma concentrations which may lead to loss of virologic
response and possible resistance to COMPLERA.
CYP3A inhibitors: Drugs that inhibit CYP3A may increase
rilpivirine plasma concentrations.
Drugs increasing gastric pH may significantly decrease
rilpivirine plasma concentrations and lead to loss of virologic
response and possible resistance to COMPLERA.
Use of proton pump inhibitors with COMPLERA is contraindicated.
Antacids should be administered =2 hours before or =4 hours after
H2 receptor antagonists should be administered =12
hours before or =4 hours after COMPLERA.
Drugs affecting renal function: Coadministration of COMPLERA
with drugs that reduce renal function or compete for active tubular
secretion may increase concentrations of emtricitabine and tenofovir.
Prescribing information: Consult the full Prescribing
Information for COMPLERA for more information on potentially
significant drug interactions, including clinical comments.
Pregnancy and Breastfeeding
Pregnancy Category B: There are no adequate and well-controlled
studies in pregnant women. Use during pregnancy only if potential
benefits justifies the potential risk. An Antiretroviral Pregnancy
Registry has been established.
Breastfeeding: Emtricitabine and tenofovir have been detected
in human milk. Because of both the potential for HIV transmission and
the potential for serious adverse reactions in nursing infants,
mothers should be instructed not to breastfeed.
DOSAGE AND ADMINISTRATION
Adults: One tablet taken orally once daily with food.
Renal Impairment: Do not use in patients requiring dose
adjustment or patients with estimated CrCl <50 mL/min.
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 and South America, Europe and
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
risk that healthcare providers in the United States and European Union
may not see advantages of switching virologically suppressed HIV
patients to Complera/Eviplera and may therefore be reluctant to
prescribe the product. 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, 2013, 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 Complera and Truvada, including BOXED
WARNING for both products, is available at www.Gilead.com.
EU Summaries of Product Characteristics for Eviplera and Truvada are
available at http://www.ema.europa.eu.
Complera, Eviplera, and Truvada are registered trademarks of Gilead
Sciences, Inc., or its related companies.
Edurant is a registered trademark of Janssen R&D Ireland.
For more information on Gilead Sciences, please visit the company's
website at www.gilead.com,
follow Gilead on Twitter (News - Alert) (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
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