First supportive care treatment approved for patients with
thrombocytopenia with chronic hepatitis C to allow the initiation and
maintenance of interferon-based therapy
SAN DIEGO -- (Business Wire)
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) partner
GlaxoSmithKline (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 interferon-based
therapy. 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.
“This is a tremendous achievement for this field of medicine. Otherwise
very sick patients, who had little to no therapeutic options, will now
have an opportunity to potentially receive treatment for hepatitis C. We
commend GSK's PROMACTA team, and particularly Drs. Arning, Amado and
Paoletti, for their leadership and commitment to driving PROMACTA to
this regulatory success,” commented John Higgins, President and Chief
Executive Officer of Ligand Pharmaceuticals. “We are extremely pleased
with the decision by the FDA, and look forward to the near-term launch
of PROMACTA for this important new indication.”
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 ≥3X 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
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 US
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 U.S. 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
About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company that develops and acquires assets
it believes will generate royalty revenues and, under its lean corporate
cost structure, produce sustainable profitability. Ligand has a diverse
asset portfolio addressing the unmet medical needs of patients for a
broad spectrum of diseases including thrombocytopenia, multiple myeloma,
diabetes, hepatitis, muscle wasting, dyslipidemia, anemia, and
osteoporosis. Ligand’s Captisol® platform technology is a
patent protected, chemically modified cyclodextrin with a structure
designed to optimize the solubility and stability of drugs. Ligand has
established multiple alliances with the world's leading pharmaceutical
companies including GlaxoSmithKline, Merck, Pfizer, Eli Lilly & Company,
Baxter International, Bristol-Myers Squibb, Celgene, Onyx
Pharmaceuticals, Lundbeck Inc., and The Medicines Company, among others.
Please visit www.captisol.com
for more information on Captisol. For more information on Ligand, please
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This news release contains certain forward-looking statements by Ligand
that involve risks and uncertainties and reflect Ligand's judgment as of
the date of this release. These statements include those related to the
potential launch of and commercial sales of PROMACTA (eltrombopag).
Actual events or results may differ from Ligand's expectations. There
can be no assurance GlaxoSmithKline, or any of our other partners will
continue clinical development of any compound(s); that clinical
development will be successful; that future clinical trial data will be
favorable or that such trials will confirm any improvements over other
products or lack of negative impacts; that drugs will receive required
regulatory approvals or that they will be commercially successful
therapies, provide new options or be successfully marketed; that our
partner portfolio will continue to mature, that our business will
continue to grow or that shareholder value will increase, that the FDA
will accept any filing, that any future milestone or royalty payments
will be received, or that if any future milestones or royalties are
received that they will not be subject to sharing obligations with any
third party. The failure to meet expectations with respect to any of the
foregoing matters may reduce Ligand's stock price. Additional
information concerning these and other risk factors affecting Ligand's
business can be found in prior press releases available via www.ligand.com
as well as in Ligand's public periodic filings with the Securities and
Exchange Commission at www.sec.gov.
Ligand disclaims any intent or obligation to update these
forward-looking statements beyond the date of this release. This caution
is made under the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995.
Ligand Pharmaceuticals Incorporated
John L. Higgins, President and
Jennifer Capuzelo, Investor Relations
Source: Ligand Pharmaceuticals Incorporated
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