|[June 13, 2014]
Ligand Partner GSK Announces Results of Phase 3 PETIT2 Study of Eltrombopag (Promacta™/Revolade™) in Pediatric Patients with Chronic Immune Thrombocytopenia
SAN DIEGO --(Business Wire)--
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces that
its partner, GlaxoSmithKline (GSK) plc, presented the results from the
Phase 3 PETIT2 study evaluating the efficacy of eltrombopag vs.
placebo in pediatric patients with chronic immune (idiopathic)
thrombocytopenic purpura (cITP). Eltrombopag - marketed as Promacta™ in
the U.S. and as Revolade™ in Europe and other countries across the world
- met its primary endpoint, achieving a statistically significant
improvement in platelet counts with almost 40 percent of patients
treated with eltrombopag attaining a consistent platelet response for 6
of 8 weeks compared to placebo (39.7 percent vs. 3.4 percent,
The PETIT2 study results were highlighted today as part of a Press
Briefing and Oral Presentation at the European Hematology Association
Annual Congress in Milan, Italy.
GSK also announced that it is moving forward with planned regulatory
submissions for a pediatric indication in cITP later this year.
Efficacy results for PETIT2 were consistent across age cohorts. The
safety profile was consistent with the established profile for
eltrombopag and no new safety concerns were observed. The most common
adverse events (AEs) occurring most frequently in the eltrombopag arm
included nasopharyngitis, rhinitis, cough and respiratory tract
infection. Grade 3/4 AEs occurred in 12.7 percent of patients treated
with eltrombopag and 10.3 percent of patients in the placebo group.
Serious AEs were reported in 8 percent of eltrombopag-treated patients
vs. 14 percent in the placebo arm.
Additional results from an early phase study of eltrombopag in
previously treated pediatric patients with cITP were also presented at
the European Hematology Association Annual Congress.
Immune (idiopathic) thrombocytopenic purpura (ITP) - characterized by a
low platelet count - affects as many as 5 in 100,000 children each year.1
While many children with ITP do not require treatment and/or their
disease resolves, up to 30 percent of patients experience persistent
disease at 12 months and are diagnosed with cITP.2, 3,4
Patients with pediatric cITP are at a high risk of severe bleeding.
PETIT2 was 2-part, double-blind, randomized placebo-controlled and
open-label study to investigate the efficacy, safety and tolerability of
eltrombopag in pediatric patients with previously treated cITP. The
multi-center study enrolled 93 subjects at 38 centers in 14 countries.
The primary objective of the study was to assess the efficacy of
eltrombopag, relative to placebo, in achieving platelet counts of =50
Gi/L among pediatric patients with previously treated cITP for at least
12 months. The initial phase of the study compared eltrombopag to
placebo for 13 weeks. All study participants were then treated with
eltrombopag in the second phase of the study (through to week 24).
About Eltrombopag (Promacta™/Revolade™)
Eltrombopag is not approved or licensed anywhere in the world for use in
chronic immune (idiopathic) thrombocytopenic purpura in the pediatric
For full US Prescribing Information for Promacta® (eltrombopag),
including Boxed Warning, please visit: https://www.gsksource.com/gskprm/htdocs/documents/PROMACTA-PI-MG-COMBINED.PDF.
For the European Union (EU) Summary of Product Characteristics (SPC) for
Revolade® (eltrombopag) in approved indications, please visit http://health.gsk.com/.
Promacta™ and Revolade™ are trademarks of the GSK group of companies.
Important Safety Information for Eltrombopag
WARNING: RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONIC
In patients with chronic hepatitis C, eltrombopag in combination with
interfern and ribavirin may increase the risk of hepatic decompensation.
Eltrombopag can cause liver enzyme elevations. Measure serum ALT, AST,
and bilirubin prior to initiation of eltrombopag, every 2 weeks during
the dose adjustment phase, and monthly following establishment of a
stable dose. Eltrombopag inhibits UGT1A1 and OATP1B1, which may lead to
indirect hyperbilirubinemia. If bilirubin is elevated, perform
fractionation. Evaluate abnormal serum liver tests with repeat testing
within 3 to 5 days. If the abnormalities are confirmed, monitor serum
liver tests weekly until resolved or stabilized.
Discontinue eltrombopag 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:
progressively increasing; or persistent for =4 weeks; or accompanied by
increased direct bilirubin; or accompanied by clinical symptoms of liver
injury or evidence for hepatic decompensation.
If the potential benefit for reinitiating treatment with eltrombopag is
considered to outweigh the risk for hepatotoxicity, then consider
cautiously reintroducing eltrombopag and measure serum liver tests
weekly during the dose adjustment phase. Hepatotoxicity may reoccur if
eltrombopag is reinitiated. If liver tests abnormalities persist, worsen
or recur, then permanently discontinue eltrombopag.
Thrombotic/thromboembolic complications may result from increases in
platelet counts with eltrombopag. 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 eltrombopag to
patients with known risk factors for thromboembolism. To minimize the
risk for thrombotic/thromboembolic complications, do not use eltrombopag
in an attempt to normalize platelet counts. Follow the dose adjustment
guidelines to achieve and maintain target platelet counts.
In the 3 controlled clinical trials in chronic ITP, cataracts developed
or worsened in 15 (7%) patients who received 50 mg eltrombopag daily and
8 (7%) placebo-group patients. In the extension trial, cataracts
developed or worsened in 4% of patients who underwent ocular examination
prior to therapy with eltrombopag.
Cataracts were observed in toxicology studies of eltrombopag in rodents.
Perform a baseline ocular examination prior to administration of
eltrombopag and, during therapy with eltrombopag, regularly monitor
patients for signs and symptoms of cataracts.
In patients with chronic ITP, monitor serum liver tests (see
Hepatotoxicity section). During therapy with eltrombopag, assess
complete blood counts (CBCs) with differentials, including platelet
counts, weekly until a stable platelet count has been achieved. Monitor
platelet counts monthly thereafter. Obtain CBCs with differentials,
including platelet counts, weekly for at least 4 weeks following
discontinuation of eltrombopag.
Eltrombopag 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 3 placebo-controlled clinical
trials in chronic ITP patients (=3% and greater than placebo) for
eltrombopag versus placebo were: nausea (9% vs. 3%), diarrhea (9% vs.
7%), upper respiratory tract infection (7% vs. 6%), vomiting (6% vs.
<1%), increased ALT (5% vs. 3%), myalgia (5% vs. 2%), urinary tract
infection (5% vs. 3%), oropharyngeal pain (4% vs. 3%), increased AST (4%
vs. 2%), pharyngitis (4% vs. 2%), back pain (3% vs. 2%), influenza (3%
vs. 2%), paresthesia (3% vs. 2%), and rash (3% vs. 2%).
About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company with a business model that is
based upon the concept of developing or acquiring royalty revenue
generating assets and coupling them to a lean corporate cost structure.
Ligand's goal is to produce a bottom line that supports a sustainably
profitable business. By diversifying our portfolio of assets across
numerous technology types, therapeutic areas, drug targets and industry
partners, we offer investors an opportunity to invest in the
increasingly complicated and unpredictable pharmaceutical industry. In
comparison to its peers, we believe Ligand has assembled one of the
largest and most diversified asset portfolios in the industry with the
potential to generate revenue in the future. These therapies address the
unmet medical needs of patients for a broad spectrum of diseases
including diabetes, hepatitis, muscle wasting, Alzheimer's disease,
dyslipidemia, anemia, asthma 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, Onyx
Pharmaceuticals (a subsidiary of Amgen Inc.), Merck, Pfizer, Baxter
International, Eli Lilly & Co. and Spectrum (News - Alert) Pharmaceuticals. Please
for more information on Captisol. For more information on Ligand, please
Follow Ligand on Twitter (News - Alert) @Ligand_LGND.
1 Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George
JN.Am J Hematol. 2010 Mar;85(3):174-80. doi: 10.1002/ajh.21616.
El-Bostany E, El-Ghoroury E, and El-Ghafar E. Anti-Beta 2 Glycoprotein I
in childhood immune thrombocytopenic purpura. Blood Coagulation and
3 BCSH, (British
Committee for Standards in Haematology). Guidelines for the
investigation and management of idiopathic thrombocytopenic purpura in
adults, children and in pregnancy. Br J Haematol. 2003;120:574-596.
Walker R.W., Walker W. Idiopathic thrombocytopenia, initial illness and
long term follow up. Archives of Disease in Childhood. 1984;59:316-322.
This news release contains forward-looking statements by Ligand that
involve risks and uncertainties and reflect Ligand's judgment as of the
date of this release. These forward-looking statements include comments
regarding eltrombopag, data analysis and evaluation of eltrombopag,
utility or potential benefits to patients, the potential commercial
market for eltrombopag and plans for continued development and further
studies of eltrombopag. Actual events or results may differ from
Ligand's expectations. For example, there can be no assurance that other
trials or evaluations of eltrombopag will be favorable or that they will
confirm results of previous studies, that data evaluation will be
completed or demonstrate any hypothesis or endpoint, that eltrombopag
will provide utility or benefits to certain patients, that any
presentations will be favorably received, that eltrombopag will be
useful, that marketing applications will be filed or, if filed,
approved, or that clinical or commercial development of eltrombopag will
be initiated, completed or successful or that our rights to eltrombopag
will not be successfully challenged. 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 can be found in prior press releases available at www.ligand.com
as well as in public periodic filings with the Securities and Exchange
Commission, available at www.sec.gov.
Ligand disclaims any intent or obligation to update these
forward-looking statements beyond the date of this press release. This
caution is made under the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995.
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