-
Tasigna is the first and only
second-generation tyrosine kinase inhibitor approved in the EU for
the treatment of Ph+ CML-CP in children
-
Approval builds on a series of
Tasigna regulatory milestones, including addition of Treatment-free
Remission (TFR) data to EU label for adults with Ph+
CML-CP
-
Demonstrates Novartis'
continuing commitment to CML patients
Basel, November 20, 2017
- Novartis announced today that the European
Commission (EC) approved Tasigna® (nilotinib)
for the treatment of pediatric patients with newly diagnosed
Philadelphia chromosome-positive chronic myeloid leukemia in the
chronic phase (Ph+ CML-CP) and pediatric patients with Ph+ CML-CP
with resistance or intolerance to prior therapy including imatinib.
Tasigna is the only second-generation tyrosine kinase inhibitor
(TKI) currently approved in the European Union (EU) for the
treatment of Ph+ CML-CP in children. The approval follows a
positive opinion issued by the European Medicines Agency's (EMA)
Committee for Medicinal Products for Human Use (CHMP) on September
14, 2017 and applies to all EU member states.
"Treatment options for children with CML have
historically been limited, and with this new indication an unmet
need has been addressed," said Bruno Strigini, CEO, Novartis
Oncology. "Data from two prospective studies demonstrated Tasigna
is safe and effective in patients as young as two years old, which
is consistent with the established safety profile of Tasigna in
adults."
This expanded indication is based on two
prospective studies of nilotinib in children with Ph+ CML-CP, which
were part of a formal "pediatric investigation plan" agreed upon
with the EMA. A total of 69 pediatric patients received nilotinib.
These pediatric patients were aged 2 to 18 years and diagnosed with
either newly diagnosed Ph+ CML-CP or Ph+ CML-CP with resistance or
intolerance to prior therapy including imatinib. In the newly
diagnosed CML patients, the major molecular response (MMR; BCR
ABL/ABL <=0.1% International Scale [IS]) rate was 60.0%
(95% confidence interval [CI]: 38.7, 78.9) at 12 cycles, with 15
patients achieving MMR. In patients with resistance or intolerance
to prior therapy including imatinib, the MMR rate was 40.9% (95%
CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR. In
newly diagnosed CML patients, the cumulative MMR rate was 64.0% by
cycle 12. In patients with resistance or intolerance to prior
therapy including imatinib, the cumulative MMR rate was 47.7% by
cycle 12[1],[2].
In pediatric patients, adverse reactions observed
were generally consistent with those observed in adults, with the
exception of hyperbilirubinemia (Grade 3/4: 13.0%), a condition
where there is too much bilirubin in the blood, and transaminase
elevation (AST Grade 3/4: 1.4%, ALT Grade 3/4: 8.7%) which were
reported at a higher frequency than in adult patients. No deaths
were reported on treatment or after treatment discontinuation in
both studies[1],[2].
This is the latest in a series of regulatory
milestones for Tasigna. In June, Novartis achieved an important
milestone for the Ph+ CML community when Tasigna became the first
and only TKI to include information on stopping therapy in adult
patients with Ph+ CML-CP in both the first-line setting and after
switching from imatinib in the EU label and several other labels
throughout the world. Novartis continues to follow the science to
advance and reimagine the future of CML.
About Ph+ CML
CML is a type of cancer in which the body produces cancerous white
blood cells. Almost all patients with CML have an abnormality known
as the Philadelphia chromosome, which produces a protein called
BCR-ABL. BCR-ABL causes malignant white blood cells to proliferate.
Worldwide, CML is responsible for approximately 10% to 15% of all
adult cases of leukemia, with an incidence of one to two cases per
100,000 people per year.
Novartis Commitment to
CML
Novartis ongoing research in Ph+ CML has helped transform the
disease from a fatal leukemia to a chronic condition in most
patients. The company maintains an unwavering commitment to
scientific innovation and access to care for patients worldwide. As
an organization committed to patients, Novartis continues to
reimagine CML by pursuing ambitious goals with courage, passion and
commitment to the global CML community.
About Tasigna
(nilotinib)
Tasigna (nilotinib) is approved in more than 122 countries for the
treatment of chronic phase and accelerated phase Philadelphia
chromosome-positive chronic myelogenous leukemia (Ph+ CML) in adult
patients resistant or intolerant to at least one prior therapy,
including Glivec® (imatinib)*, and in more than 110 countries for
the treatment of adult patients with newly diagnosed Ph+ CML in
chronic phase. Tasigna is approved in the European Union (EU) for
the treatment of Ph+ CML in the chronic phase in pediatric patients
with resistance or intolerance to prior therapy including Glivec
and for the treatment of pediatric patients with newly diagnosed
Ph+ CML in the chronic phase.
IMPORTANT SAFETY INFORMATION for
TASIGNA® (nilotinib) Capsules
Use with caution in patients with uncontrolled or significant
cardiac disease and in patients who have or may develop
prolongation of QTc. Low levels of potassium or magnesium must be
corrected prior to Tasigna administration. Monitor closely for an
effect on the QTc interval. Baseline ECG is recommended prior to
initiating therapy and as clinically indicated. Cases of sudden
death have been reported in clinical studies in patients with
significant risk factors. Avoid use of concomitant drugs known to
prolong the QT interval and strong CYP3A4 inhibitors. Avoid food 2
hours before and 1 hour after taking dose. Reactivation of
hepatitis B can occur in patients who are chronic carriers of this
virus after receiving TKI treatment.
Use with caution in patients with liver
impairment, with a history of pancreatitis and with total
gastrectomy. Patients with rare hereditary problems of galactose
intolerance, severe lactase deficiency or glucose-galactose
malabsorption should not use Tasigna. Tasigna may cause fetal harm
in pregnant women. If pregnancy is planned during the
treatment-free remission phase, the patient must be informed of a
potential need to re-initiate treatment with Tasigna during
pregnancy. Women taking Tasigna should not breastfeed.
Cases of cardiovascular events included ischemic
heart disease-related events, peripheral arterial occlusive
disease, and ischemic cerebrovascular events have been reported.
Serious cases of hemorrhage from various sites including
gastrointestinal were reported in patients receiving Tasigna. Grade
3 or 4 fluid retention including pleural effusion, pericardial
effusion, ascites and pulmonary edema have been reported. Cases of
tumor lysis syndrome have been reported in Tasigna-treated patients
who were resistant or intolerant to prior CML therapy.
In pediatric patients the long-term effects of
prolonged treatment with Tasigna is unknown.
Eligible patients who are confirmed to express the
typical BCR-ABL transcripts, e13a2/b2a2 or e14a2/b3a2, can be
considered for treatment discontinuation. Frequent monitoring of
BCR-ABL transcript levels in patients eligible for treatment
discontinuation must be performed with a quantitative diagnostic
test validated to measure molecular response levels with a
sensitivity of at least MR4.5 (BCR-ABL/ABL <=0.0032% IS).
BCR-ABL transcript levels must be assessed prior to and during
treatment discontinuation. Loss of major molecular response
(MMR=BCR-ABL/ABL <=0.1%IS) or confirmed loss of MR4 (two
consecutive measures separated by at least 4 weeks showing loss of
MR4 (MR4=BCR-ABL/ABL <=0.01%IS)) will trigger treatment
re-initiation within 4 weeks of when loss of remission is known to
have occurred. It is crucial to perform frequent monitoring of
BCR-ABL transcript levels and complete blood count with
differential in order to detect possible loss of remission. For
patients who fail to achieve MMR after three months of treatment re
initiation, BCR-ABL kinase domain mutation testing should be
performed.
The most frequent Grade 3 or 4 adverse events are
hematological (neutropenia, thrombocytopenia, anemia) which are
generally reversible and usually managed by withholding Tasigna
temporarily or dose reduction. Chemistry panels, including
electrolytes, lipid profile, liver enzymes, and glucose should be
checked prior to therapy and periodically. Tasigna can cause
increases in serum lipase. The most frequent non-hematologic
adverse events were rash, pruritus, nausea, fatigue, headache,
alopecia, myalgia, constipation and diarrhea.
Musculoskeletal pain, myalgia, pain in extremity,
arthralgia, bone pain and spinal pain may occur upon discontinuing
treatment with Tasigna within the framework of attempting
treatment-free remission.
Please see full Prescribing Information including
Boxed WARNING at www.tasigna.com.
About Glivec
(imatinib)
Glivec (imatinib) is approved in more than 110 countries, for the
treatment of adult patients in all phases of Philadelphia
chromosome-positive (Ph+) CML, for the treatment of patients with
KIT (CD117)-positive GIST, which cannot be surgically removed
and/or have metastasized and for the treatment of adult patients
following complete surgical removal of KIT+ GIST.
Not all indications are available in every
country.
Glivec Important Safety
Information
Glivec is contraindicated in patients who are hypersensitive to
imatinib or any of the excipients.
Glivec can cause fetal harm when administered to a
pregnant woman. Women should not become pregnant, and should be
advised of the potential risk to the unborn child.
Glivec has been associated with severe edema
(swelling) and serious fluid retention. Cytopenias (anemia,
neutropenia, thrombocytopenia) are common, generally reversible and
usually managed by withholding Glivec or dose reduction. Monitor
blood counts regularly. Severe congestive heart failure and left
ventricle dysfunction, severe liver problems including cases of
fatal liver failure and severe liver injury requiring liver
transplants have been reported. Caution in patients with cardiac
dysfunction and hepatic dysfunction. Monitor carefully.
Reactivation of hepatitis B can occur in patients who are chronic
carriers of this virus after receiving TKI treatment.
Bleeding may occur. Severe gastrointestinal (GI)
bleeding has been reported in patients with KIT+ GIST. Skin
reactions, hypothyroidism in patients taking levothyroxine
replacement, GI perforation, in some cases fatal, tumor lysis
syndrome which can be life threatening have also been reported with
Glivec. Correct dehydration and high uric acid levels prior to
treatment. Long-term use may result in potential liver, kidney,
and/or heart toxicities; immune system suppression may also result
from long-term use. In patients with hypereosinophilic syndrome and
heart involvement, cases of heart disease have been associated with
the initiation of Glivec therapy. Growth retardation has been
reported in children taking Glivec. The long-term effects of
extended treatment with Glivec on growth in children are
unknown.
The most common side effects include fluid
retention, muscle cramps or pain and bone pain, abdominal pain,
loss of appetite, vomiting, diarrhea, decreased hemoglobin,
abnormal bleeding, nausea, fatigue and rash. Glivec should be taken
with food and a large glass of water.
Please see full Prescribing Information available
at www.glivec.com.
*Known as Gleevec® (imatinib mesylate) tablets in
the US, Canada and Israel.
Disclaimer
This press release contains 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, payor
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 121,000 full-time-equivalent
associates. Novartis products are sold in approximately 155
countries around the world. For more information, please visit
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References
[1] Hochhaus A, et al.
Leukemia. 2016;30:1044-1054
[2] Giles F, et al.
Leukemia. 2013;27:107-112.
# # #
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