-
Nearly 70% of patients
maintained platelet counts of >=30×109/L
without rescue therapy for prolonged periods, reducing the overall
risk of bleeding
-
More than one-third of patients
permanently stopped one or more concomitant ITP medications
(including corticosteroids, danazol, azathioprine)
-
Study establishes long-term
safety profile for and demonstrates treatment benefit with
Revolade
Basel, October 18, 2017 -
Novartis today announced long-term study results supporting the
positive safety and efficacy of Revolade (eltrombopag) in adults
with chronic/persistent (enrolling patients that were 6 or more
months from diagnosis) immune (idiopathic) thrombocytopenia (ITP)
were published online in Blood. The EXTEND
study found that a majority of patients maintained a substantial
clinical response and many no longer needed concomitant ITP
medications. The research evaluated patients for up to 8 years of
continuous treatment (median exposure of 2.4 years)[1],[2].
ITP is a rare and potentially serious blood
disorder where the blood doesn't clot as it should due to a low
number of platelets. As a result, patients with ITP experience
bruising, bleeding and, in rare cases, serious hemorrhaging that
can be fatal[3]. The goal of treatment in chronic/persistent ITP is
to maintain a safe platelet count that reduces the risk of
bleeding[1],[3].
"The EXTEND data published in Blood validate Revolade as an important oral treatment
option that, by often increasing platelet counts, significantly
decreased bleeding rates and reduced the need for concurrent
therapies in certain patients with chronic/persistent immune
thrombocytopenia," said lead author James Bussel, M.D., professor
emeritus of pediatrics at Weill Cornell Medicine. "With this
information, physicians can better optimize long-term disease
management for appropriate patients living with this chronic
disease."
The efficacy results of EXTEND demonstrated that
median platelet counts were elevated to >=50×109/L within two
weeks of Revolade treatment, with median platelet counts
>50×109/L maintained
for more than four years. Post-baseline, overall bleeding rates
declined and the majority of bleeding that occurred during the
study was Grade 1 or 2 according to the World Health Organization
bleeding scale. Some patients (39%) were capable of reducing or
permanently stopping one or more concomitant ITP medications
without the need for rescue therapy, many of which sustained
reduction for at least 24 weeks[1],[2],[4].
"We conducted this trial, the largest of its kind
in adult patients, to ensure that clinicians have comprehensive
data on hand as they work with their ITP patients to make treatment
decisions," said Vas Narasimhan, M.D., Global Head Drug Development
and Chief Medical Officer, Novartis. "The EXTEND results reinforce
Revolade as a trusted treatment option that can be used over the
long-term for those living with this chronic and rare disease."
Overall, the safety profile of Revolade was
consistent with previous studies. The most common adverse events
were headache (28%), nasopharyngitis (25%) and upper respiratory
tract infection (23%). During treatment on EXTEND, 6% of patients
experienced thromboembolic events[1],[2],[4].
About the EXTEND Clinical
Trial
EXTEND, an open-label extension study of four trials (TRA100773A,
TRA100773B, TRA102537/RAISE and TRA108057/REPEAT) of Revolade,
enrolled 302 adults with chronic/persistent ITP (6 or more months
from diagnosis) who had received prior therapy for their ITP, and
is the largest study of its kind. To qualify for the prior trials,
patients must have had thrombocytopenia for at least 6 months
(chronic ITP was previously defined as thrombocytopenia for 6 or
more months).The objectives were to assess the safety and efficacy
of long-term treatment with Revolade, including the proportion of
patients achieving stable platelet counts during treatment with
Revolade; maximum duration of platelet count elevation
>=50×109/L or
>=30×109/L during
treatment with Revolade, and the effect of Revolade on reducing
and/or sparing concomitant ITP therapies, while maintaining a
platelet count >=50×109/L[1],[2].
The study allowed each patient to achieve an
individualized dose and schedule of eltrombopag based upon their
platelet counts in the desired range between 50 to 200 Gi/L.
Therefore, patients who were enrolled in EXTEND must have completed
the treatment and follow-up periods as defined in previous protocol
and must have not experienced eltrombopag-related toxicity or other
drug intolerance on prior eltrombopag study even if resolved. In
addition, patients who discontinued from a previous study due to
toxicity were not eligible unless they received placebo[1],[2].
Revolade was started at a dose of 50 mg/day and
titrated to 25-75 mg/day or less often based on platelet counts.
Maintenance dosing continued after minimization of concomitant ITP
medication and optimization of Revolade dosing. The overall median
duration of exposure was 2.37 years (range, 2 days to 8.76 years)
and mean average daily dose was 50.2 (range, 1-75) mg/day[1],[2].
One hundred thirty five adult patients (45%) completed the study
and 75 adult patients (25%) were treated for four or more years.
Most patients were aged <65 years, female, and had platelet
counts <30×109/L at
baseline. About one-third were using concomitant medications at
baseline, and 53% had received three or more prior ITP
therapies[1],[2]. In addition, 91% (276/302) of patients achieved
platelet counts >=30×109/L without
rescue treatment, and 86% (259/302) achieved platelet counts
>=50×109/L without
rescue treatment[1],[2],[4].
Grade 3 and 4 adverse events (AEs) occurred in 26%
and 6% of patients, respectively. Grade 3 cataracts occurred in
four (1%) patients and Grade 3 pain in extremity in six (2%)
patients. Grade 3 AEs occurring in three (<1%) patients each
included diarrhea, headache, migraine, dyspnea, decreased platelet
count, and menorrhagia; those occurring in five (2%) patients each
included pneumonia, fatigue, back pain, increased alanine
aminotransferase, increased aspartate aminotransferase, anemia, and
hypertension. Grade 4 anemia and thrombocytopenia occurred in three
(<1%) and four (1%) patients, respectively. All other Grade 4
events occurred in one patient each[1],[2].
About Chronic/Persistent
ITP
Chronic/persistent ITP is a rare and potentially serious blood
disorder that is characterized by the improper functioning or
destruction of platelets, which are blood cells that allow the
blood to clot properly[3]. People who have ITP often have purple
bruises or tiny red or purple dots on the skin[3]. They also
display symptoms such as nosebleeds, bleeding from the gums during
dental work, or other bleeding that is hard to stop[3]. The
potential for drops in platelet counts may also cause emotional
distress and may result in a hindered ability to do work or
embarrassment due to visible symptoms[5].
ITP is classified by duration from diagnosis into:
acute (0-3 months), persistent (3-12 months duration) and chronic
(>12 months duration). Chronic/persistent ITP is more likely to
occur in adults, and women are affected two to three times more
often than men[3].
The goal of treatment in chronic/persistent ITP is
to maintain a safe platelet count that reduces the risk of
bleeding. Treatment is determined by the severity of the symptoms.
In most cases, drugs that alter the immune system's attack on the
platelets are prescribed to help manage bleeding and bruising in
adults.
About Eltrombopag
Eltrombopag, marketed as Promacta® in the
United States and Revolade® in
countries outside the US, 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, approved in over 45 countries worldwide for the
treatment of patients with severe aplastic anemia (SAA) who are
refractory to other treatments, and also approved in more than 50
countries for the treatment of thrombocytopenia in patients with
chronic hepatitis C to allow them to initiate and maintain
interferon-based therapy. Eltrombopag is approved in the US and in
the European Union for the treatment of thrombocytopenia in
pediatric patients 1 year and older with chronic immune
(idiopathic) thrombocytopenia (ITP) who have had an insufficient
response to corticosteroids and immunoglobulins.
Important Safety Information for
Revolade® (eltrombopag)
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, or 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
extremities, 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).
Disclaimer
This press release contains forward-looking statements, including
"forward-looking statements" within the meaning of the United
States Private Securities Litigation Reform Act of 1995.
Forward-looking statements can generally be identified by words
such as "potential," "can," "will," "plan," "expect," "anticipate,"
"look forward," "believe," "committed," "investigational,"
"pipeline," "launch," or similar terms, or by express or implied
discussions regarding potential marketing approvals, new
indications or labeling for the investigational or approved
products described in this press release, or regarding potential
future revenues from such products. You should not place undue
reliance on these statements. Such forward-looking statements are
based on our current beliefs and expectations regarding future
events, and are subject to significant known and unknown risks and
uncertainties. Should one or more of these risks or uncertainties
materialize, or should underlying assumptions prove incorrect,
actual results may vary materially from those set forth in the
forward-looking statements. There can be no guarantee that the
investigational or approved products described in this press
release will be submitted or approved for sale or for any
additional indications or labeling in any market, or at any
particular time. Nor can there be any guarantee that such products
will be commercially successful in the future. In particular, our
expectations regarding such products could be affected by, among
other things, the uncertainties inherent in research and
development, including clinical trial results and additional
analysis of existing clinical data; regulatory actions or delays or
government regulation generally; our ability to obtain or maintain
proprietary intellectual property protection; the particular
prescribing preferences of physicians and patients; global trends
toward health care cost containment, including government, payer
and general public pricing and reimbursement pressures; general
economic and industry conditions, including the effects of the
persistently weak economic and financial environment in many
countries; safety, quality or manufacturing issues, and other risks
and factors referred to in Novartis AG's current Form 20-F on file
with the US Securities and Exchange Commission. Novartis is
providing the information in this press release as of this date and
does not undertake any obligation to update any forward-looking
statements contained in this press release as a result of new
information, future events or otherwise.
About
Novartis
Novartis provides innovative healthcare solutions that address the
evolving needs of patients and societies. Headquartered in Basel,
Switzerland, Novartis offers a diversified portfolio to best meet
these needs: innovative medicines, cost-saving generic and
biosimilar pharmaceuticals and eye care. Novartis has leading
positions globally in each of these areas. In 2016, the Group
achieved net sales of USD 48.5 billion, while R&D throughout
the Group amounted to approximately USD 9.0 billion. Novartis Group
companies employ approximately 119,000 full-time-equivalent
associates. Novartis products are sold in approximately 155
countries around the world. For more information, please visit
http://www.novartis.com.
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For Novartis multimedia content, please visit
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For questions about the site or required registration, please
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James Bussel, M.D. has received
research support payments for his service on an advisory board as
well as participated in speakers' bureaus sponsored by Novartis
Pharmaceuticals.
References
[1] Wong R, et al. Safety and efficacy of long-term treatment of
chronic/persistent ITP with eltrombopag: final results of the
EXTEND study. Blood. October 2017; Online
First Edition
[2] Bussel J, et al. Final Safety and Efficacy Results from the
EXTEND Study: Treatment with Eltrombopag (EPAG) in Adults with
Chronic Immune Thrombocytopenia (cITP). 2016 Congress of the
European Hematology Association (EHA). Copenhagen,
Denmark.
[3] Immune Thrombocytopenia. US National Institutes of Health
website http://www.nhlbi.nih.gov/book/export/html/4917. Accessed
October 16, 2017.
[4] Novartis Data on File.
[5] Mathias S, et al. "Impact of Chronic Immune Thrombocytopenic
Purpura (ITP) on health-related quality of life: a conceptual model
starting with the patient perspective." Health and
quality of life outcomes 6.1(2008):1.
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