Ligand Announces Positive Regulatory Opinion in Europe for Revolade for Chronic Immune Thrombocytopenic Purpura
SAN DIEGO--
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) today
announced that its partner GlaxoSmithKline (NYSE: GSK) has received a
positive opinion for Revolade(R) (eltrombopag/Promacta(R)) from the European
Medicines Agency's Committee for Medicinal Products for Human Use (CHMP)
for the oral treatment of thrombocytopenia (reduced platelet count) in
adults with the blood disorder chronic immune (idiopathic)
thrombocytopenic purpura (ITP).
The CHMP has recommended the marketing authorization of eltrombopag in
the European Union for the treatment of ITP in adult patients who have
had their spleen removed, and who do not respond to other treatments,
such as corticosteroids and immunoglobulins therapies. Eltrombopag may
also be considered as a second-line treatment for adult patients where
surgery to remove their spleen is contraindicated.
"Approval in Europe presents an expanded market opportunity for
eltrombopag and is an exciting development for Ligand as it continues to
validate Ligand's success in contributing to the discovery of novel and
important commercial therapies," said John L. Higgins, President and
Chief Executive Officer of Ligand Pharmaceuticals. "Eltrombopag enjoys
in excess of 10 years remaining patent life in both the U.S. and Europe,
and the European approval of Revolade expands the commercial potential
for the drug. We commend GSK for their clinical and regulatory successes
and commitment to developing eltrombopag for other indications."
ITP patients experience bruising and bleeding and, in some cases,
serious hemorrhages, which can be fatal. ITP may also affect a patient's
quality of life, as it is often associated with fatigue and depression1
and a fear of bleeding may limit everyday activities.2
Traditional treatments with corticosteroids, immunoglobulins or
splenectomy (removal of the spleen) all have potential drawbacks for
chronic treatment of ITP patients.5, 6, 7
Eltrombopag significantly increases platelet counts
The positive opinion from CHMP is based on two Phase III randomized,
double-blind, placebo-controlled clinical trials (TRA100773B8
and RAISE TRA1025379) and two open-label studies (REPEAT
TRA10805710 and EXTEND TRA10532511) in adults who
have previously received treatment for chronic ITP. The studies showed
that the patients treated with eltrombopag (plus the standard of care)
experienced significant increases in platelet counts, a reduction in the
incidence of bleeding and an improvement in quality of life, compared
with those receiving placebo (plus the standard of care) 8,9,11.
Eltrombopag treatment has also allowed patients to reduce the dose of
their concomitant medications, such as steroids.9
In clinical trials, eltrombopag was well-tolerated.8,12 In
some cases, nausea and vomiting were recorded in the eltrombopag group
and not in the placebo group.8 Elevation of liver enzymes was
also seen, but these were mostly mild, reversible and not accompanied by
any clinically significant symptoms that would indicate impaired liver
function.8
Eltrombopag is the first oral platelet generator
Eltrombopag is an oral, non-peptide, thrombopoietin receptor agonist. It
stimulates the proliferation and differentiation of megakaryoctes,
resulting in an increase in platelet counts. Megakaryocytes are the bone
marrow cells that give rise to blood platelets.13
About eltrombopag
Eltrombopag was given accelerated approval by the U.S. Food and Drug
Administration (FDA) under the trade name Promacta(R) in
November 2008, for the treatment of chronic ITP in adults who have had
an insufficient response to corticosteroids, immunoglobulins or surgical
removal of the spleen. Eltrombopag is also approved under the trade name
Revolade(R) in Venezuela, Kuwait, Chile and Russia. In
addition, orphan designation was granted by the European Commission for
eltrombopag for the treatment of ITP on August 3, 2007.14 Eltrombopag
was discovered as a result of a research collaboration between GSK and
Ligand Pharmaceuticals, and developed by GSK.
About chronic ITP
Chronic ITP is a serious condition, where patients have low platelet
levels in the blood. Platelets are essential to normal clotting, so
patients with ITP are at increased risk of bleeding, and may develop
bruises and experience nose or gum bleeds, have blood in the urine or
feces, abnormally heavy menstrual bleeding, or other types of bleeding
that is difficult to stop.14 Although very rare in
occurrence, bleeding in the brain is potentially fatal.15
Quality of life is adversely affected in patients with chronic ITP, with
a fear of bleeding limiting patients' daily activities.2
Fatigue and depression are, also, often associated with the disease.1
Revolade(R) and Promacta(R) are registered trade marks
of the GlaxoSmithKline group of companies. Information based on GSK's
press release.
About Ligand Pharmaceuticals
Ligand discovers and develops new drugs that address critical unmet
medical needs of patients with muscle wasting, frailty, hormone-related
diseases, osteoporosis, inflammatory diseases, anemia, asthma,
rheumatoid arthritis and psoriasis. Ligand's proprietary drug discovery
and development programs are based on advanced cell-based assays,
gene-expression tools, ultra-high throughput screening and one of the
world's largest combinatorial chemical libraries. Ligand has strategic
alliances with major pharmaceutical and biotechnology companies,
including Bristol-Myers Squibb, Celgene, Cephalon, GlaxoSmithKline,
Merck and Pfizer. With more than 20 molecules in various stages of
development, Ligand utilizes proprietary technologies for identifying
drugs with novel receptor and enzyme drug targets.
References
1. Platelet Disorder Support Association (PDSA): About ITP.
http://www.pdsa.org/itp-information/index.html Accessed November 2009.
Mathias SD, Gao SK, Miller KL, et al. Impact of chronic immune
2. thrombocytopenic purpura (ITP) on health-related quality of life: a
conceptual model starting with the patient perspective. Health Qual Life
Outcomes 2008; 6:13.
National Heart, Lung, and Blood Institute: Diseases and Conditions
3. Index.http://www.nhlbi.nih.gov/health/dci/Diseases/Itp/ITP_WhatIs.html.
Accessed May 2009.
4. Cines DB, McMillan R. Management of Adult Idiopathic Thrombocytopenic
Purpura. Annu Rev Med, 2004;56:425-52
5. Stasi R, Provan D. Management of Immune Thrombocytopenic Purpura in
Adults. Mayo Clin Proc. 2004;79:504-522
6. McMillan R, Durette C. Long-term outcomes in adults with chronic ITP
after splenectomy failure. Blood. 2004;104: 956-960
Bussel JB, Eldor A, Kelton JG, et al. IGIV-C, a novel intravenous
7. immunoglobulin: evaluation of safety, efficacy, mechanisms of action,
and impact on quality of life. Thromb Haemost. 2004; 91:771-8
Bussel JB, Provan D, Shamsi T, et al. Effect of eltrombopag on platelet
8. counts and bleeding during treatment of chronic idiopathic
thrombocytopenic purpura: a randomised, double-blind, placebo-controlled
trial. Lancet 2009;373:641-8.
Cheng G, Saleh M, Bussel J, et al. Oral eltrombopag for the long-term
9. treatment of patients with chronic idiopathic thrombocytopenic purpura:
results of a Phase III, double-blind, placebo-controlled study (RAISE).
Blood 2008;112:400. [ASH Annual Meeting Abstracts].
Psaila B, Bussel J, Vasey S, et al. Efficacy and safety of repeated
10. intermittent treatment with eltrombopag in patients with chronic ITP.
Abstract 0294 presented at the 13th congress of the European Haematology
Association, June 2008.
Saleh M, Bussel JB, Cheng G, et al. Eltrombopag is efficacious in
11. patients with refractory chronic idiopathic thrombocytopenic purpura
(ITP) - data from the EXTEND Study. Blood 2008; 112:401 [ASH Annual
Meeting Abstracts].
Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of
12. chronic idiopathic thrombocytopenic purpura. N Engl J Med
2007;357:2237-47.
Erickson-Miller CL, Delorme E, Tian SS, et al. Preclinical activity of
13. eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor
agonist. Stem Cells 2009; 27:424-30.
EMEA. Committee for Orphan Medicinal Products. Public summary of
14. positive opinion for orphan designation of eltrombopag olamine for the
treatment of idiopathic thrombocytopenic purpura, 2009:1-4.
National Heart, Lung, and Blood Institute: Diseases and Conditions
15. Index. http://www.nhlbi.nih.gov/health/dci/Diseases/Itp/ITP_WhatIs.html.
Accessed November 2009.
Caution Regarding Forward-Looking Statements
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 and other drug candidates, 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 or other
product candidates 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 or other
product candidates will provide utility or benefits to certain patients,
that any presentations will be favorably received, that eltrombopag or
other product candidates will be useful, that marketing applications
will be filed or, if filed, approved, or that clinical or commercial
development of these product candidates will be initiated, completed or
successful or that our rights to eltrombopag and other related product
candidates 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.
Source: Ligand Pharmaceuticals Incorporated
Released December 18, 2009