Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the
U.S. Food and Drug Administration (FDA) has approved a change to
the prescribing information for Letairis® (ambrisentan 5 mg and 10
mg tablets), the company’s once-daily treatment to improve exercise
ability and delay clinical worsening in pulmonary arterial
hypertension (PAH, WHO Group 1) patients with predominantly WHO
Functional Class II-III symptoms. This change removes language
concerning the potential risk of liver injury from the Boxed
Warning. In conjunction with this label update, PAH patients
receiving Letairis are no longer required to obtain monthly liver
function tests.
The FDA approved the new labeling based on its review of
post-marketing data reflecting use of Letairis over more than 7,800
patient years, which were collected through the Letairis Education
and Access Program (LEAP). These data were consistent with clinical
trial data used to support the registration of Letairis. During
12-week controlled clinical trials, the incidence of liver function
abnormalities was 0 percent on Letairis and 2.3 percent on
placebo.
“I am encouraged by these post-marketing data, which reflect the
use of ambrisentan since its approval in 2007. These data are
consistent with the results we have observed in controlled
studies,” said Ronald J. Oudiz, MD, Professor of Medicine, David
Geffen School of Medicine at UCLA and Director, Liu Center for
Pulmonary Hypertension, Los Angeles Biomedical Research Institute
at Harbor-UCLA Medical Center. “This change will be tremendously
helpful to both patients and the staff of specialist centers who
diligently support them. Pulmonary arterial hypertension is a very
complex disease at the best of times, so any steps to simplify care
will be warmly welcomed.”
Gilead will continue to offer the full services of LabSync,
which manages the administrative requirements associated with
laboratory testing, to all patients enrolled in LEAP.
Important Safety Information Including
Boxed Warning
Letairis is contraindicated in pregnancy. Because of
the risk of birth defects, Letairis continues to have a Boxed
Warning and can be prescribed and dispensed only through a special
restricted distribution program (Letairis Education and Access
Program [LEAP]). Only prescribers and pharmacies registered
with LEAP may prescribe and distribute Letairis to patients who are
enrolled in and meet all the conditions of LEAP. Because Letairis
may cause fetal harm if taken during pregnancy, pregnancy must be
excluded before the start of treatment and must be prevented during
treatment and for one month after stopping treatment by the use of
two acceptable methods of contraception unless the patient has had
a tubal sterilization or chooses to use a Copper T380A IUD or LNg
20 IUS, in which case no additional contraception is needed.
Monthly pregnancy tests must be obtained. Letairis must not be
administered to a pregnant woman.
Peripheral edema occurred more frequently in elderly patients
(age greater than or equal to 65 years) receiving Letairis (29
percent; 16/56) compared to placebo (4 percent; 1/28). Peripheral
edema is a known class effect of endothelin receptor antagonists.
In addition, there have been post-marketing reports of fluid
retention occurring within weeks after starting Letairis, which
required intervention with a diuretic, fluid management, or, in
some cases, hospitalization for decompensating heart failure.
Decreases in sperm count have been observed in patients taking
endothelin receptor antagonists.
Decreases in hemoglobin have been observed within the first few
weeks of treatment with Letairis. It is recommended to measure
hemoglobin prior to initiation of Letairis, at one month and
periodically thereafter. Initiation of Letairis therapy is not
recommended for patients with clinically significant anemia.
If patients develop acute pulmonary edema during initiation of
therapy with vasodilating agents such as Letairis, the possibility
of pulmonary veno-occlusive disease should be considered, and if
confirmed, Letairis should be discontinued.
The most common adverse events that occurred at a higher
frequency among Letairis-treated patients compared to placebo
included (placebo-adjusted frequency): peripheral edema (6
percent), nasal congestion (4 percent), sinusitis (3 percent),
flushing (3 percent), palpitations (3 percent), nasal pharyngitis
(2 percent), abdominal pain (2 percent), constipation (2 percent),
dyspnea (1 percent) and headache (1 percent). During 12-week
controlled clinical trials, the incidence of aminotransferases
elevations greater than three times the upper limit of normal (ULN)
were 0 percent on Letairis and 2.3 percent on placebo. In practice,
cases of hepatic injury should be carefully evaluated for
cause.
In post-marketing experience, elevations of liver
aminotransferases (ALT, AST) have been reported with Letairis use.
In most cases alternative causes of the liver injury could be
identified (heart failure, hepatic congestion, hepatitis, alcohol
use, hepatotoxic medications). Other endothelin receptor
antagonists have been associated with elevations of
aminotransferases, hepatotoxicity and cases of liver failure. It is
recommended to discontinue Letairis if aminotransferase elevations
greater than five times the ULN are observed or if aminotransferase
elevations are accompanied by bilirubin greater than two times the
ULN or if there are signs or symptoms of liver dysfunction and
other causes are excluded. Tests for serum liver enzymes should be
ordered and reviewed as clinically indicated since some members of
this pharmacologic class are hepatotoxic.
Multiple-dose co-administration of Letairis and cyclosporine
resulted in an approximately two-fold increase in Letairis exposure
in healthy volunteers. Therefore, the dose of Letairis should be
limited to 5 mg once-daily when co-administered with
cyclosporine.
Studies with human liver tissue indicate that Letairis is
metabolized by CYP3A, CYP2C19 and uridine 5'-diphosphate
glucuronosyltransferases (UGTs) 1A9S, 2B7S and 1A3S. In vitro
studies suggest that Letairis is a substrate of the Organic Anion
Transport Protein (OATP) and a substrate, but not an inhibitor of
P-glycoprotein (P-gp). Drug interactions might be expected because
of these factors. However, a clinically relevant interaction has
been demonstrated only with cyclosporine. Letairis does not inhibit
or induce phase I or II drug metabolizing enzymes at clinically
relevant concentrations.
It is recommended to initiate Letairis treatment at 5 mg
once-daily with or without food, and to consider increasing the
dose to 10 mg once-daily if 5 mg is tolerated. Tablets should not
be split, crushed or chewed. Letairis is not recommended in
patients with moderate or severe hepatic impairment. There is no
information on the use of Letairis in patients with mild hepatic
impairment. However, exposure to Letairis may be increased in these
patients.
Full prescribing information for Letairis is available at
www.gilead.com and at
http://www.letairis.com/downloads/LETAIRIS_prescribing_information.pdf.
About Letairis and Indication and
Usage
Letairis is a once-daily treatment for pulmonary arterial
hypertension (PAH, WHO Group 1) to improve exercise ability and
delay clinical worsening. Studies establishing effectiveness of
Letairis included predominantly patients with WHO Functional Class
II-III symptoms and etiologies of idiopathic or heritable PAH (64
percent) or PAH associated with connective tissue diseases (32
percent). Clinical worsening is defined as the first occurrence of
death, lung transplantation, hospitalization for PAH, atrial
septostomy, study withdrawal due to the addition of other PAH
therapeutic agents or study withdrawal due to early escape.
Letairis is an endothelin receptor antagonist that has a high
affinity for the endothelin type-A (ETA) receptor. Activation of
the ETA receptor by endothelin-1 (ET-1), a small peptide hormone,
leads to vasoconstriction (narrowing of blood vessels) and cell
proliferation. The clinical impact of high selectivity for ETA is
not known. Endothelin concentrations are higher in the lung tissue
of PAH patients, thus suggesting that ET-1 may play a critical role
in the pathogenesis or progression of PAH.
About the Letairis Education and Access
Program (LEAP)
Because of the risks of birth defects, Letairis is available
only through a special restricted distribution program called the
Letairis Education and Access Program (LEAP) by calling
1-866-664-LEAP (1-866-664-5327). Only prescribers and pharmacies
registered with LEAP are able to prescribe and distribute Letairis.
In addition, Letairis may be dispensed only to patients who are
enrolled in and meet all conditions of LEAP.
About LabSync
LabSync is a service that manages the administrative
requirements associated with laboratory testing for patients
enrolled in LEAP, including assistance with scheduling laboratory
appointments, addressing lab-related insurance issues and providing
healthcare providers with complete patient histories of
LEAP-related laboratory results.
About Pulmonary Arterial Hypertension
(WHO Group 1)
PAH is a debilitating disease characterized by constriction of
the blood vessels in the lungs leading to high pulmonary arterial
pressures. These high pressures make it difficult for the heart to
pump blood through the lungs to be oxygenated. Patients with PAH
suffer from shortness of breath as the heart struggles to pump
against these high pressures, causing such patients to ultimately
die of heart failure. PAH can occur with no known underlying cause,
or it can occur secondary to diseases such as connective tissue
disease, congenital heart defects, cirrhosis of the liver and HIV
infection. PAH afflicts approximately 200,000 patients
worldwide.
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 Asia Pacific.
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 whether or not this label change will
impact physicians’ decisions to prescribe Letairis over other
competing products. As a result, our sales of Letairis may not
increase in response to the label change. 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, 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.
Letairis is a registered trademark of Gilead
Sciences, Inc.
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