Gilead Sciences 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 inhibitor-containing
regimen.
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.
CONTRAINDICATIONS
* 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 considered.
* 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.
ADVERSE REACTIONS
* 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%.
DRUG INTERACTIONS
* 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
COMPLERA.
* H[2 ]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 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 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 (@GileadSciences) or call Gilead
Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Market News and Data brought to you by Benzinga APIs© 2024 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.
Comments
Loading...
Benzinga simplifies the market for smarter investing
Trade confidently with insights and alerts from analyst ratings, free reports and breaking news that affects the stocks you care about.
Join Now: Free!
Already a member?Sign in