Issued: Monday 19 November 2012, London UK and Philadelphia US
- First supportive care treatment approved for patients with thrombocytopenia with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy
GlaxoSmithKline plc [LSE/NYSE: GSK] announced today that the U.S.
Food and Drug Administration (FDA) has approved PROMACTA for the
treatment of thrombocytopenia (low blood platelet counts) in patients
with chronic hepatitis C to allow them to initiate and maintain
PROMACTA is the first supportive care
treatment available to patients who are ineligible or poor candidates
for interferon-based therapy due to their low blood platelet counts.
PROMACTA in combination with interferon-based therapy has been shown to
improve a patient’s chance of achieving a sustained virologic response
(SVR) or viral cure.
There are limitations to the use of PROMACTA in patients suffering
from chronic hepatitis C-associated thrombocytopenia. These include:
- PROMACTA should not be used in an attempt to normalize platelet counts;
- PROMACTA should be used only in patients with chronic hepatitis C
whose degree of thrombocytopenia prevents the initiation of interferon
therapy or limits the ability to maintain optimal interferon-based
- Safety and efficacy have not been established in combination with
direct-acting antiviral agents approved for treatment of chronic
hepatitis C genotype 1 infection.
“Chronic hepatitis C is a significant public health issue,” said
Paolo Paoletti, M.D., President, GlaxoSmithKline Oncology. “Some
chronic hepatitis C patients suffer from low blood platelet counts.
Commonly prescribed interferon-based therapies can worsen the problem of
low blood platelet counts. Today’s FDA approval of PROMACTA gives
doctors a tool to address the low platelet challenge. This means more
chronic hepatitis C patients may be able to start and stay on
interferon-based therapy. That gives these patients a better chance to
achieve a viral cure.”
The approval for PROMACTA is based on results from ENABLE 1 and 2
(Eltrombopag to INitiate and Maintain Interferon Antiviral Treatment to
Benefit Subjects with Hepatitis C related Liver DiseasE), two Phase III
randomized, double-blind, placebo-controlled, multicenter studies, which
collectively enrolled 1,521 patients with platelet counts
<75,000/µL. ENABLE 1 utilized peginterferon alfa-2a (PEGASYS®) plus ribavirin for antiviral treatment and ENABLE 2 utilized peginterferon alfa-2b (PEGINTRON®) plus ribavirin.
Important Safety Information for PROMACTA
PROMACTA may cause hepatotoxicity. PROMACTA, in combination
with interferon and ribavirin in patients with chronic hepatitis C, may
increase the risk of hepatic decompensation. Patients receiving therapy
with PROMACTA must have regular monitoring of serum liver tests (see
Laboratory Monitoring). Discontinue PROMACTA if ALT levels increase to
≥3X upper limit of normal (ULN) in patients with normal liver function
or ³3X baseline in patients with pre-treatment elevations in
transaminases and are: progressive; or persistent for ≥4 weeks; or
accompanied by increased direct bilirubin; or accompanied by clinical
symptoms of liver injury or evidence of hepatic decompensation.
Reinitiating treatment with PROMACTA is not recommended and should be
considered only with close medical supervision and under exceptional
circumstances where the potential benefit outweighs the risk.
Additional Safety Information Regarding Risk of Hepatotoxicity:
Reinitiating treatment with PROMACTA is not recommended. If the
potential benefit for reinitiating treatment with PROMACTA is considered
to outweigh the risk for hepatotoxicity, then cautiously reintroduce
PROMACTA and measure serum liver tests weekly during the dose adjustment
phase. If liver test abnormalities persist, worsen or recur, then
permanently discontinue PROMACTA.
Chronic hepatitis C patients with cirrhosis may be at risk of hepatic
decompensation and death when treated with alfa interferons. Monitor
patients with low albumin levels or with MELD score ≥10 at baseline.
Thrombotic/thromboembolic complications may result from increases in
platelet counts with PROMACTA. Reported thrombotic/thromboembolic
complications included both venous and arterial events and were observed
at low and at normal platelet counts. Consider the potential for an
increased risk of thromboembolism when administering PROMACTA to
patients with known risk factors for thromboembolism. To minimize the
risk for thrombotic/thromboembolic complications, do not use PROMACTA in
an attempt to normalize platelet counts. Follow the dose adjustment
guidelines to achieve and maintain target platelet counts.
In 2 controlled clinical trials in patients with chronic hepatitis C
and thrombocytopenia, 3% (31/955) treated with PROMACTA experienced a
thrombotic event compared to 1% (5/484) on placebo. The majority of
events were of the portal venous system (1% in patients treated with
PROMACTA versus <1% for placebo).
In a controlled trial in non-ITP thrombocytopenic patients with
chronic liver disease undergoing elective invasive procedures (N=292),
seven thrombotic complications (six patients) were reported within the
group that received PROMACTA and three thrombotic complications (two
patients) within the placebo group. All of the thrombotic complications
reported in the group that received PROMACTA were portal vein
thrombosis, with thrombotic complications occurring in five of the six
patients at a platelet count above 200 x 109/L. PROMACTA is not indicated for the treatment of thrombocytopenia in patients with CLD in preparation for invasive procedures.
PROMACTA must not be taken within 4 hours of any medications or
products containing polyvalent cations such as antacids, dairy products,
and mineral supplements.
The most common adverse reactions in 2 randomized placebo-controlled
clinical trials in thrombocytopenic patients with chronic hepatitis C
(≥10% and greater than placebo) for PROMACTA versus placebo were: anemia
(40% vs. 35%), pyrexia (30% vs. 24%), fatigue (28% vs. 23%), headache
(21% vs. 20%), nausea (19% vs. 14%), diarrhea (19% vs. 11%), decreased
appetite (18% vs. 14%), influenza‐like illness (18% vs. 16%), asthenia
(16% vs. 13%), insomnia (16 % vs. 15%), cough (15% vs. 12%), pruritus
(15% vs. 13%), chills (14% vs. 9%), myalgia (12% vs. 10%), alopecia (10%
vs. 6%), and peripheral edema (10% vs. 5%).
PROMACTA has both a BOXED WARNING and Medication Guide. Full
Prescribing Information for physicians and Important Safety Information
for consumers will be available soon at http://www.gsk.com/products/index.htm.
In the meantime, patients and physicians should visit the FDA Web site, www.fda.gov for important safety information.
About Chronic Hepatitis C Patients and Thrombocytopenia
Approximately 4.2 million people in the US have chronic hepatitis C,
the most common blood-borne virus. It is estimated that up to 3.5% of
these patients have platelet counts <75,000/µL, which could make them
ineligible to start or maintain their interferon-based therapy.
About PROMACTA® (eltrombopag)
Eltrombopag, marketed under the brand names PROMACTA® in the U.S. and Revolade®
in Europe and Rest-of-World, is a thrombopoietin receptor agonist
approved in 90 countries around the world as a treatment for
thrombocytopenia in patients with chronic immune (idiopathic)
thrombocytopenic purpura (ITP).
In the United States, PROMACTA® is already indicated for
the treatment of thrombocytopenia in patients with chronic ITP who have
had an insufficient response to corticosteroids, immunoglobulins or
GlaxoSmithKline – one of the world’s leading research-based
pharmaceutical and healthcare companies – is committed to improving the
quality of human life by enabling people to do more, feel better and
live longer. For further information please visit www.gsk.com
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