– Odefsey is the Smallest Single Tablet HIV Regimen –
Gilead Sciences, Inc. (NASDAQ:GILD) today announced that the U.S. Food
and Drug Administration (FDA) has approved Odefsey®
(emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg or
R/F/TAF) for the treatment of HIV-1 infection in certain patients.
Emtricitabine and tenofovir alafenamide are from Gilead Sciences and
rilpivirine is from Janssen Sciences Ireland UC, one of the Janssen
Pharmaceutical Companies of Johnson & Johnson (Janssen). Odefsey is
Gilead’s second TAF-based regimen to receive FDA approval and represents
the smallest pill of any single tablet regimen for the treatment of HIV.
Odefsey is indicated as a complete regimen for the treatment of HIV-1
infection in patients 12 years of age and older who have no
antiretroviral treatment history and HIV-1 RNA levels less than or equal
to 100,000 copies per mL. Odefsey is also indicated as replacement for a
stable antiretroviral regimen in those who are virologically-suppressed
(HIV-1 RNA less than 50 copies per mL) for at least six months with no
history of treatment failure and no known substitutions associated with
resistance to the individual components of Odefsey. No dosage adjustment
of Odefsey is required in patients with estimated creatinine clearance
greater than or equal to 30 mL per minute.
Odefsey has a boxed warning in its product label regarding the
risks of lactic acidosis/severe hepatomegaly with steatosis, and post
treatment acute exacerbation of hepatitis B. See below for important
safety information.
Photos and multimedia gallery available at www.GileadHIVMedia.com.
TAF is a novel targeted prodrug of tenofovir that has demonstrated high
antiviral efficacy similar to and at a dose less than one-tenth that of
Gilead’s Viread® (tenofovir disoproxil fumarate, TDF). TAF
has also demonstrated improvement in surrogate laboratory markers of
renal and bone safety as compared to TDF in clinical trials in
combination with other antiretroviral agents. Data show that because TAF
enters cells, including HIV-infected cells, more efficiently than TDF,
it can be given at a much lower dose and there is 90 percent less
tenofovir in the bloodstream.
“As people are living longer with HIV, there is an increasing need to
develop new treatments that are tolerable and help address long-term
health for patients,” said John C. Martin, PhD, Chairman and Chief
Executive Officer, Gilead Sciences. “Odefsey’s safety, efficacy and
tolerability profile offers a new treatment option to support the needs
of a range of patients and represents Gilead’s commitment to innovation
in the field of HIV.”
The approval is supported by a bioequivalence study demonstrating that
Odefsey achieved similar drug levels of emtricitabine and TAF in the
blood as Genvoya® (elvitegravir 150 mg/cobicistat 150
mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg or E/C/F/TAF) and
similar drug levels of rilpivirine as Edurant® (rilpivirine
25 mg). The safety, efficacy and tolerability of Odefsey is supported by
clinical studies of rilpivirine-based therapy (administered as R+F/TDF
or R/F/TDF) and F/TAF-based therapy (administered as E/C/F/TAF) in a
range of patients with HIV, including treatment-naïve adults and
adolescents, virologically suppressed adults who switched from PI-,
NNRTI- and INSTI-based regimens and virologically suppressed adults with
mild-to-moderate renal impairment.
The Odefsey approval is part of an ongoing development and
commercialization agreement between Gilead and Janssen, first
established in 2009. Under this agreement, Gilead is responsible for the
manufacturing, registration, distribution and commercialization of the
product in most countries, while Janssen will distribute it in
approximately 17 markets and have co-detailing rights in several key
markets, including the United States. The original agreement was
established for the development and commercialization of Complera®,
marketed as Eviplera® in the European Union, and expanded in
2014 to include Odefsey.
Odefsey does not cure HIV infection or AIDS.
Patient Assistance Programs
Gilead’s U.S. Advancing Access® program provides assistance
to appropriate patients in the United States who are uninsured,
underinsured or who need financial assistance to pay for their
medications, including Odefsey.
The program offers information and assistance for patients, including:
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Access to agents who can provide information related to coverage and
insurance-related questions.
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The Advancing Access Copay Coupon Program, which provides co-pay
assistance for eligible patients with private insurance who need
assistance paying for out-of-pocket medication costs.
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The Advancing Access Patient Assistance Program and Truvada®
Medication Assistance Program, which will provide Gilead medications
at no charge for eligible patients with no other insurance options.
Additionally, Gilead is working closely with the ADAP Crisis Task Force,
as the company has done for each of its other HIV medications, to
provide discounts to state AIDS Drug Assistance Programs (ADAPs) that
will help ensure access to Odefsey for patients who receive medications
through these programs.
Information about how to apply for any of these forms of assistance can
be found at www.GileadAdvancingAccess.com
or by calling 1-800-226-2056 between 9:00 a.m. and 8:00 p.m. EST.
Important U.S. Safety Information for Odefsey
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and
POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
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Lactic acidosis and severe hepatomegaly with steatosis, including
fatal cases, have been reported with the use of nucleoside analogs in
combination with other antiretrovirals.
-
Odefsey is not approved for the treatment of chronic hepatitis B
virus (HBV) infection, and the safety and efficacy of Odefsey have not
been established in patients coinfected with HIV-1 and HBV. Severe
acute exacerbations of hepatitis B have been reported in patients who
are coinfected with HIV-1 and HBV and have discontinued products
containing emtricitabine and/or tenofovir disoproxil fumarate (TDF),
and may occur with discontinuation of Odefsey. 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 Odefsey. If appropriate, initiation of
anti-hepatitis B therapy may be warranted.
Contraindications
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Coadministration: Do not use with drugs that induce CYP3A or
increase gastric pH as this may lead to loss of efficacy and possible
resistance to Odefsey or the NNRTI class. Do not use with
carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin,
rifapentine, proton pump inhibitors (e.g., dexlansoprazole,
esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole),
systemic dexamethasone (>1 dose) and St. John’s wort.
Warnings and precautions
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Skin and hypersensitivity reactions: Severe skin and
hypersensitivity reactions have been reported with the use of
rilpivirine-containing regimens, including cases of Drug Reaction with
Eosinophilia and Systemic Symptoms (DRESS). In rilpivirine clinical
trials, most rashes were Grades 1-2 and occurred in the first 4-6
weeks of treatment; Grades 2-4 rash occurred in 1% of subjects.
Discontinue Odefsey immediately if severe skin or hypersensitivity
reactions occur, including severe rash or rash accompanied by fever,
blisters, mucosal involvement, conjunctivitis, facial edema,
angioedema, hepatitis or eosinophilia. Monitor clinical status
including laboratory parameters and initiate appropriate therapy.
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Loss of virologic response due to drug interactions: See
Contraindications and Drug Interactions sections. Consider the
potential for drug interactions prior to and during Odefsey therapy
and monitor for adverse reactions.
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Prolongation of QTc interval: Rilpivirine doses 3 and 12 times
higher than the recommended dose can prolong the QTc interval.
Consider alternatives to Odefsey in patients at higher risk for
Torsade de Pointes or when coadministered with a drug with known risk
of Torsade de Pointes.
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Depressive disorders: Evaluate patients with severe depressive
symptoms to assess if symptoms are due to Odefsey and if the risks of
continued treatment outweigh the benefits. In rilpivirine adult
clinical trials (N=686), the incidence of depressive disorders was 9%,
Grades 3-4 depressive disorders was 1%, discontinuation due to
depressive disorders was 1%, and suicidal ideation and suicide attempt
was reported in 4 and 2 subjects, respectively. In a rilpivirine
adolescent clinical trial (N=36), the incidence of depressive
disorders was 19%, Grades 3-4 depressive disorders was 6%, and
suicidal ideation and suicide attempt were reported in 1 subject.
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Hepatotoxicity: Hepatic adverse events have been
reported, including cases of hepatic toxicity, in patients without
pre-existing hepatic disease or other identifiable risk factors. In
patients with hepatic abnormalities (e.g., hepatitis, elevated
liver-associated tests), order laboratory tests before starting
treatment and monitor for hepatotoxicity during treatment; consider
testing and monitoring in all patients.
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Fat redistribution or accumulation has been observed in
patients receiving antiretroviral therapy.
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Immune reconstitution syndrome, including the occurrence of
autoimmune disorders with variable time to onset, has been reported.
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New onset or worsening renal impairment: Cases of acute renal
failure and Fanconi syndrome have been reported with the use of
tenofovir prodrugs. In clinical trials of emtricitabine and tenofovir
alafenamide with elvitegravir and cobicistat, there have been no cases
of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not
initiate Odefsey in patients with estimated creatinine clearance
(CrCl) <30 mL/min. Patients with impaired renal function and/or taking
nephrotoxic agents (including NSAIDs) are at increased risk of
renal-related adverse reactions. Discontinue Odefsey in patients who
develop clinically significant decreases in renal function or evidence
of Fanconi syndrome.
Renal monitoring: In all patients,
monitor CrCl, urine glucose, and urine protein prior to initiating and
during therapy. In patients with chronic kidney disease, additionally
monitor serum phosphorus.
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Bone loss and mineralization defects: Decreases in bone mineral
density (BMD) have been reported with the use of tenofovir prodrugs.
Consider monitoring BMD in patients with a history of pathologic
fracture or risk factors for bone loss. Mineralization defects,
including osteomalacia associated with PRT, have been reported with
the use of TDF-containing products.
Adverse reactions
-
Most common adverse reactions with rilpivirine (incidence ≥2%,
Grades 2-4) are depressive disorders (2%), insomnia (2%) and headache
(2%); and with emtricitabine and tenofovir alafenamide (incidence
≥10%, all grades) is nausea (10%).
Drug interactions
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Prescribing information: Consult the full prescribing
information for Odefsey for more information on Contraindications,
Warnings, and potentially significant drug interactions, including
clinical comments.
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Metabolism: Drugs that induce CYP3A or P-gp and drugs that
increase gastric pH can decrease the concentrations of components of
Odefsey. Drugs that inhibit CYP3A or P-gp can increase the
concentrations of components of Odefsey.
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QT prolonging drugs: Consider alternatives to Odefsey in
patients taking a drug with known risk of Torsade de Pointes.
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Drugs affecting renal function: Coadministration of Odefsey
with drugs that reduce renal function or compete for active tubular
secretion may increase concentrations of emtricitabine and tenofovir
and the risk of adverse reactions.
Dosage and administration
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Dosage: Patients 12 years and older (≥35 kg): 1 tablet taken
orally once daily with a meal.
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Renal impairment: Not recommended in patients with CrCl <30
mL/min.
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Testing prior to initiation: Test patients for HBV infection
and assess CrCl, urine glucose and urine protein.
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Testing after initiation: In virologically-suppressed patients,
additional monitoring of HIV-1 RNA and regimen tolerability is
recommended.
Pregnancy and lactation
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Pregnancy: There are insufficient data on the use of Odefsey
during pregnancy. In animal studies, no adverse developmental effects
were observed with the components of Odefsey. An Antiretroviral
Pregnancy Registry has been established.
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Lactation: Women infected with HIV-1 should be instructed not
to breastfeed, due to the potential for HIV-1 transmission.
About Gilead
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. Gilead has operations in more than 30
countries worldwide, with headquarters in Foster City, California.
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 physicians may not see the benefits of prescribing Odefsey. 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
Annual Report on Form 10-K for the year ended December 31, 2015, 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, including BOXED WARNING,
for Odefsey is available at www.gilead.com.
U.S. Full Prescribing Information, including BOXED WARNING,
for Genvoya, Stribild, Complera, Truvada and Viread are available at www.gilead.com.
Odefsey, Genvoya, Stribild, Complera, Truvada, Eviplera,
Viread and Advancing Access are registered trademarks of Gilead
Sciences, Inc., or its related companies.
Edurant is a registered trademark of Janssen Sciences Ireland UC.
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.
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