Ligand Partner GlaxoSmithKline Receives FDA Approval for New Indication for
First supportive care treatment approved for patients with thrombocytopenia
with chronic hepatitis C to allow the initiation and maintenance of
SAN DIEGO -- November 19, 2012
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 therapy; and
*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
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
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 10^9/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
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 splenectomy.
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 visit www.ligand.com.
Follow Ligand on Twitter @Ligand_LGND.
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 CEO
Jennifer Capuzelo, Investor Relations
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