Revolade® Approved in EU as First in Class Therapy for Children Aged 1 Year and Above with Chronic ITP

  • Revolade is marketed as Promacta® in the United States
  • EU approval of Revolade expands treatment options for pediatric
    patients aged 1 year and above with chronic ITP who have not responded
    to other therapies
  • Two formulations approved: once-daily tablet and oral suspension
    formulation designed for younger children who may not be able to
    swallow tablets
  • For about one in four children with ITP, a disorder of low blood
    platelet count and potential bleeding, the condition becomes chronic1,2

SAN DIEGO–(BUSINESS WIRE)–Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces that
the European Commission (EC) has approved Revolade® (eltrombopag), a
Novartis product, for the treatment of pediatric (aged 1 year and above)
chronic immune (idiopathic) thrombocytopenic purpura (ITP) patients who
are refractory to other treatments (e.g. corticosteroids,
immunoglobulins). The approval includes the use of tablets as well as a
new oral suspension formulation of Revolade, which is designed for
younger children who may not be able to swallow tablets. Revolade was
approved by the EC in 2010 for use in adults with the same condition.

ITP is a rare blood disorder that affects about five in 100,000 children
each year and is characterized by a low platelet count2,3.
Because people with ITP have a low number of platelets, they may bruise
easily and experience bleeding that is hard to stop2. Chronic
ITP, defined as ongoing disease more than 12 months after diagnosis4,
occurs in 13–36% of children with ITP1. A small number of
pediatric patients with chronic ITP may be at risk of significant
bleeding5.

The approval is based on data from two double-blind, randomized,
placebo-controlled trials, including the largest Phase III clinical
trial in this patient population. In these studies, patients in the
treatment and placebo arms were permitted to use some stable maintenance
ITP therapies, per local treatment practices. Treatment with Revolade
significantly increased and sustained platelet counts among pediatric
patients with chronic ITP who were refractory to or had relapsed after
prior chronic ITP therapies, and some patients taking concomitant ITP
medications were able to reduce or discontinue their use of these
medications, primarily corticosteroids.

The EC approval applies to all 28 European Union member states, plus
Iceland, Norway and Liechtenstein.

Revolade is a once-daily oral thrombopoietin (TPO) receptor agonist that
works by inducing stimulation and differentiation of megakaryocytes
(large cells, found especially in bone marrow) from bone marrow stem
cells to increase platelet production6. In August 2015, the
U.S. Food and Drug Administration (FDA) approved a new oral suspension
formulation, which expanded use of eltrombopag to include children 1
year of age and older with chronic ITP who have had an insufficient
response to corticosteroids, immunoglobulins or splenectomy.

About the PETIT and PETIT2 Clinical Trials

PETIT is a Phase II, multi-center, three-part study to investigate the
efficacy, safety and tolerability of Revolade in pediatric patients
(ages 1 to 17 years) with previously treated chronic ITP. The trial
included patients living with ITP for six months or longer who had a
platelet count <30 Gi/L. Part one was an open label, dose finding study;
part two was double-blind and placebo-controlled, and part three was an
open-label extension. Patients in the study were permitted to use some
stable maintenance ITP therapies, per local treatment practices. The
primary efficacy outcome, which was percentage of participants who
achieved a platelet count >=50 Gi/L without rescue therapy at least once
between weeks one and six, was met by 62% and 32% of patients in the
Revolade arm and the control arm, respectively (p=0.011). The secondary
efficacy endpoint analyses demonstrated clinically meaningful benefit in
terms of decreased need for rescue treatment (13% of patients on
Revolade compared to 50% of patients in the control arm). Patients
received Revolade for a total of six months during the trial6,7.

PETIT2 is a Phase III, multi-center, two-part study to investigate the
efficacy, safety and tolerability of Revolade in pediatric patients
(ages 1 to 17 years) with previously treated chronic ITP. The trial
included patients living with chronic ITP for 12 months or longer who
also had a platelet count <30 Gi/L. Part one was randomized,
double-blind and placebo-controlled and part two was an open-label
extension. Patients in the study were permitted to use some stable
maintenance ITP therapies, per local treatment practices. The primary
efficacy outcome, which was percentage of participants who achieved a
platelet count >=50 Gi/L without rescue therapy for at least six out of
eight weeks between weeks five and 12 of part one of the study, was met
by 40% of patients treated with Revolade and 3% of patients in the
control arm (p<0.001). This result was consistent across the age
cohorts. The secondary efficacy endpoint analyses demonstrated
clinically meaningful benefit in terms of decreased need for rescue
treatment (19% of patients on Revolade compared to 24% of patients in
the control arm) during the randomized, double-blind period. Patients
were permitted to reduce or discontinue baseline ITP therapy only during
the open-label phase of the trial. In the open label eltrombopag-only
period, 15 of 87 patients were taking concomitant ITP medications at
baseline. Of these 15 patients, eight (53%) had a sustained reduction or
permanent discontinuation of at least one baseline ITP medication (seven
patients permanently discontinued and one patient had sustained
reduction for >=18 weeks). Patients received Revolade for a total of
nine months during the trial6,8.

In both studies, safety was consistent with the known safety profile of
Revolade in chronic ITP in adults and the population under study. No new
safety signals were detected. The most common adverse reactions in
pediatric chronic ITP patients 1 year and older (greater than or equal
to 10% and greater than placebo) were upper respiratory tract infection
and nasopharyngitis6,7,8.

About Chronic ITP

ITP is a blood disorder characterized by blood that does not clot as it
should due to a low number of platelets. People who have ITP often have
purple bruises or tiny red or purple dots on the skin. They also may
have nosebleeds, bleeding from the gums during dental work, or other
bleeding that’s hard to stop. In most cases, an autoimmune response is
thought to cause ITP in which a person’s immune system attacks and
destroys its own platelets2.

The two types of ITP are acute (temporary or short-term) and chronic
(long-lasting). Acute ITP mainly occurs in children, often after a viral
infection, and generally lasts less than six months. The platelet count
returns to normal within six to 12 months and treatment may not be needed2.
Chronic ITP, defined as ongoing disease more than 12 months after
diagnosis4, occurs in 13–36% of children with ITP1.
A small number of pediatric patients with chronic ITP may be at risk of
significant bleeding5.

The goal of treatment in chronic ITP for children is to maintain a safe
platelet count that reduces the risk of bleeding2. The most
commonly available and used therapies—corticosteroids and intravenous
immunoglobulin (IVIG)—are associated with side effects that are often
difficult to tolerate in a pediatric setting5,9,10.

About Revolade® (eltrombopag)

Revolade is approved in more than 100 countries worldwide for the
treatment of thrombocytopenia in adult patients with chronic immune
(idiopathic) thrombocytopenic purpura (ITP) who have had an inadequate
response or are intolerant to other treatments. Eltrombopag (marketed as
Promacta® in the USA), is approved by the US Food and Drug
Administration for once-daily use in pediatric patients 1 year and older
with chronic ITP who have had an insufficient response to
corticosteroids, immunoglobulins or splenectomy. Revolade is also
approved in over 45 countries worldwide 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. In September 2015, the European Commission approved Revolade
for the treatment of adults with severe aplastic anemia (SAA) who were
either refractory to prior immunosuppressive therapy or heavily
pretreated and are unsuitable for hematopoietic stem cell transplant.

Revolade Important Safety Information

Revolade may cause serious side effects, such as liver problems, high
platelet counts and a higher chance for blood clots, bleeding after
stopping treatment, and bone marrow problems.

Revolade may damage the liver and cause serious, even life threatening,
illness. Blood tests to check the liver are needed before taking
Revolade and during treatment. When certain antiviral treatments are
given together with Revolade for the treatment of thrombocytopenia due
to hepatitis C virus (HCV) infections, some liver problems can get worse.

A doctor will order the blood tests and any other tests required. In
some cases Revolade treatment may need to be stopped. Patients should
tell a doctor right away if they have any of these signs and symptoms of
liver problems: yellowing of the skin or the whites of the eyes
(jaundice), unusual darkening of the urine, unusual tiredness, right
upper stomach area pain.

Patients have a higher chance of getting a blood clot if their platelet
count is too high during treatment with Revolade, but blood clots can
occur with normal or even low platelet counts. Patients who have
cirrhosis of the liver are at risk of a blood clot in a blood vessel
that feeds the liver. Patients may have severe complications from some
forms of blood clots, such as clots that travel to the lungs or that
cause heart attacks or strokes. A doctor will check the patient’s blood
platelet counts, and change the dose or stop Revolade if platelet counts
get too high. Patients should tell their doctor right away if they have
signs and symptoms of a blood clot in the leg, such as swelling or
pain/tenderness of one leg.

When patients with chronic ITP stop taking Revolade, their blood
platelet count will drop back down to what it was before they started
taking Revolade. These effects are most likely to happen within 4 weeks
after patients stop taking Revolade. The lower platelet counts may
increase risk of bleeding. A doctor will check platelet counts for at
least 4 weeks after patients stop taking Revolade. Patients should tell
their doctor or pharmacist if they have any bruising or bleeding after
they stop taking Revolade.

Patients being treated for the disease may have problems with their bone
marrow. Medicines like Revolade could make this problem worse. Signs of
bone marrow changes may show up as abnormal results in blood tests. A
doctor may also carry out tests to directly check the bone marrow during
treatment with Revolade.

The most common side effects of Revolade when used to treat adult
patients with chronic ITP include headache, anemia, decreased appetite,
insomnia, cough, nausea, diarrhea, alopecia, pruritus, myalgia, pyrexia,
fatigue, influenza-like illness, asthenia, chills and peripheral edema.

The most common side effects of Revolade when used to treat pediatric
patients with chronic ITP include upper respiratory tract infection,
nasopharyngitis, cough, diarrhea, pyrexia, rhinitis, abdominal pain,
oropharyngeal pain, toothache, rash, increased AST and rhinorrhea.

The most common side effects of Revolade when used to treat patients
with chronic HCV and antiviral agents include headache, anemia,
decreased appetite, insomnia, cough, nausea, diarrhea, alopecia,
pruritus, myalgia, pyrexia, fatigue, influenza-like illness, asthenia,
chills and peripheral edema.

The most common side effects of Revolade when used to treat patients
with severe aplastic anemia (SAA) include headache, dizziness, insomnia,
cough, dyspnea, oropharyngeal pain, rhinorrhea, nausea, diarrhea,
abdominal pain, transaminases increased, ecchymosis, arthralgia, muscle
spasms, pain in extremity, fatigue, febrile neutropenia, and pyrexia.
Common side effects that may show up in blood tests include increase in
some liver enzymes and laboratory tests that may show abnormal changes
to the cells in the bone marrow.

Please see full EU Summary of Product Characteristics for Revolade
(eltrombopag).

About Ligand Pharmaceuticals

Ligand is a biopharmaceutical company focused on developing or acquiring
technologies that help pharmaceutical companies discover and develop
medicines. Our business model creates value for stockholders by
providing a diversified portfolio of biotech and pharmaceutical product
revenue streams that are supported by an efficient and low corporate
cost structure. Our goal is to offer investors an opportunity to
participate in the promise of the biotech industry in a profitable,
diversified and lower-risk business than a typical biotech company. Our
business model is based on doing what we do best: drug discovery,
early-stage drug development, product reformulation and partnering. We
partner with other pharmaceutical companies to leverage what they do
best (late-stage development, regulatory management and
commercialization) to ultimately generate our revenue. Ligand’s Captisol®
platform technology is a patent-protected, chemically modified
cyclodextrin with a structure designed to optimize the solubility and
stability of drugs. OmniAb® is a patent-protected transgenic
animal platform used in the discovery of fully human mono-and bispecific
therapeutic antibodies. Ligand has established multiple alliances,
licenses and other business relationships with the world’s leading
pharmaceutical companies including Novartis, Amgen, Merck, Pfizer,
Celgene, Gilead, Janssen, Baxter International and Eli Lilly.

Follow Ligand on Twitter @Ligand_LGND.

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 include statements regarding the size of the
patient population for ITP, Ligand’s potential revenue under its license
agreement with Novartis and Ligand’s corporate cost structure. Actual
events or results may differ from our expectations. For example, there
can be no assurances that Novartis will successfully develop or market
Revolade in the EU. 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 important risk factors affecting
Ligand (including Ligand’s current reliance on revenues based on sales
of Promacta® and Kyprolis®, and various risks to
which Ligand’s Captisol® cyclodextrin operations are subject)
can be found in Ligand’s prior press releases available at www.ligand.com
as well as in Ligand’s 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, except
as required by law. This caution is made under the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.

References

1. George JN, Woolf SH, Raskob GE. Idiopathic thrombocytopenic purpura:
a practice guideline developed by explicit methods for the American
Society of Hematology. Blood. 1996;88(1):3-40.
2. Immune
Thrombocytopenia. US National Institutes of Health website. http://www.nhlbi.nih.gov/book/export/html/4917.
Accessed October 20, 2015.
3. Fogarty PF, Segal JB. The
epidemiology of immune thrombocytopenic purpura. Curr Opin Hematol.
2007;14(5):515-519.
4. Rodeghiero F, Stasi R, Gernsheimer T, et al.
Standardization of terminology, definitions and outcome criteria in
immune thrombocytopenic purpura of adults and children: report from an
international working group. Blood. 2009;12;113(11):2386-2393.
5.
Neunert C, Lim W, Crowther M, et al. The American Society of Hematology
2011 evidence-based practice guideline for immune thrombocytopenia.
Blood. 2011;117(16):4190-4207.
6. Revolade Summary of Product
Characteristics.
7. Bussel JB, Garcia de Miguel P, Despotovic JM,
et al. Eltrombopag for the treatment of children with persistent and
chronic immune thrombocytopenia (PETIT): a randomised, multicentre,
placebo-controlled study. Lancet Haematol. 2015; published online July
29, 2015.
8. Grainger JD, Locatelli F, Chotsampancharoen T, et al.
Eltrombopag for children with chronic immune thrombocytopenia (PETIT2):
a randomised, multicentre, placebo-controlled trial. Lancet. 2015;
published online July 29, 2015.
9. Provan D, Stasi R, Newland AC,
et al. International consensus report on the investigation and
management of primary immune thrombocytopenia. Blood.
2010;115(2):168-186.
10. Cines DB, Blanchette VS. Immune
thrombocytopenic purpura. N Engl J Med. 2002;346(13):995-1008.

Contacts

Ligand Pharmaceuticals Incorporated
Todd Pettingill, (858) 550-7500
investors@ligand.com
or
LHA
Bruce
Voss, (310) 691-7100
bvoss@lhai.com