2013-09-19 07:19:02 -
Novartis International AG /
Novartis marks World CML Day with update on global research program to evaluate
whether Ph+ CML patients can live treatment-free
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* CML community recognizes September 22 as World CML Day to raise awareness of
the needs of patients living with CML
* Novartis commemorates World CML Day, announcing 100+ study sites across 40
countries now enrolling patients to its global treatment-free remission
* Treatment-free remission program evaluates whether patients can maintain
undetectable levels of disease after stopping nilotinib therapy
19, 2013 - Novartis commemorates World CML Day by announcing
the latest milestone in its unique clinical trial program evaluating the
potential for patients with Philadelphia chromosome-positive chronic myeloid
leukemia (Ph+ CML) to maintain undetectable levels of disease after stopping
drug therapy - a concept called treatment-free remission. More than 100 study
sites are now enrolling patients to the trial program.
Since 2008, organizations around the world have recognized World CML Day. The
date, September 22 or 9/22, was symbolically chosen to represent the genetic
material that is associated with CML - the missing section from chromosome 22
shifts to chromosome 9 and vice versa, in a phenomenon called
"translocation." Known as the Philadelphia chromosome, this genetic mutation
is present in about 95% of CML patients.
"As a leader in CML, Novartis is proud to support World CML Day through our
continued dedication to ongoing research in this disease," said Hervé Hoppenot,
President, Novartis Oncology. "Given that nilotinib has been shown in large
clinical trials to drive deeper levels of responses in more than twice as many
patients as imatinib, we are now looking to the next phase and exploring if
nilotinib can treat the disease to a point where drug therapy is no longer
needed, representing the next step in what may be possible for patients living
with Ph+ CML."
Over the past decades, Novartis research in Ph+ CML has helped transform the
disease from a fatal diagnosis to a chronic condition for many patients. Today,
the company continues its long-standing commitment to the global CML community.
The Novartis treatment-free remission clinical trial program* includes eight
studies that are now underway and actively enrolling Ph+ CML patients in more
than 100 global sites across 40 countries. In total, it is planned that more
than 2,500 patients will be enrolled in these studies and an estimated nearly
1,000 patients will aim to stop treatment as part of these studies.
Globally, Novartis is sponsoring four treatment-free remission studies,
* ENESTfreedom - a Phase II study in Ph+ CML patients in chronic phase who
achieved and maintained MR4.5 on nilotinib as first-line treatment. More
information, including addresses and contact information for each study
site, can be found on www.clinicaltrials.gov, identifier # NCT01784068.
* ENESTop - a Phase II study in Ph+ CML patients in chronic phase who have
achieved and maintained MR4.5 on nilotinib after switching from imatinib.
More information, including addresses and contact information for each study
site, can be found on www.clinicaltrials.gov, identifier # NCT01698905.
* ENESTpath - a Phase III study in Ph+ CML patients in chronic phase who
have switched to nilotinib from imatinib and have achieved and maintained
MR4.0. More information, including addresses and contact information for
each study site, can be found on www.clinicaltrials.gov, identifier #
* ENESTgoal - a Phase II study in Ph+ CML patients in chronic phase who
have achieved and maintained MR4.5 on nilotinib after switching from
imatinib. More information, including addresses and contact information for
each study site, can be found on www.clinicaltrials.gov, identifier #
Novartis is also providing support for four investigator-initiated studies
(STAT-2, NILst, CML V, NILO POST-STIM). These studies are led by independent
investigators in sites in Japan, Germany and France.
Stopping treatment is not a clinical recommendation and should only be attempted
in the context of a well conducted clinical study. A very important part of
these treatment-free remission studies is the inclusion of regular molecular
monitoring with International Scale Real-Time Quantitative Polymerase Chain
Reaction (IS RT-Q-PCR) testing. Once treatment is stopped molecular monitoring
is used to identify if a patient's level of disease remains in deep molecular
response or if the reintroduction of treatment is needed-.
ENESTfreedom study details
ENESTfreedom is a Phase II, single-arm, open-label study to determine if adults
with Ph+ CML can live without drug therapy after stopping treatment with
nilotinib. Eligible patients must have maintained MR4.5 with nilotinib treatment
in the first-line setting for at least two years before entering the study.
Following a one-year consolidation phase, patients who continue to sustain MR4.5
will enter the treatment-free phase. Patients will be monitored closely with
regular IS RT-Q-PCR testing.
The primary endpoint is the percentage of patients who are in major molecular
response (MMR) at 48 weeks after starting the treatment-free phase and no
restarting of nilotinib treatment.
ENESTop study details
ENESTop is a Phase II, single-arm, open-label study designed to determine if
adults with Ph+ CML can live without drug therapy after stopping treatment with
nilotinib. Eligible patients have been on treatment with nilotinib for at least
two years (with the combined time on imatinib and nilotinib for at least three
years) and have maintained MR4.5 for at least one year before entering the
treatment-free phase. Patients will be monitored closely with regular IS RT-Q-
The primary endpoint is the proportion of patients in treatment-free remission
and no loss of MMR or MR4 within the first 12 months of nilotinib cessation.
ENESTpath study details
ENESTpath is a prospective, randomized, open-label, two arm Phase III study
designed to evaluate the rate of treatment-free remission in Ph+ CML patients at
12 months after two different durations of consolidation treatment with
nilotinib. Eligible patients must have been treated with imatinib for a minimum
of two years, being at least in complete cytogenetic response, but have not
achieved MR4.0 at study start. Patients entering the study will have two years
of nilotinib treatment. If sustained MR4.0 is achieved during the second year of
nilotinib treatment, patients will be eligible to be randomized to either enter
the treatment-free remission phase immediately, or continue for another year of
consolidation with nilotinib treatment and, if still in sustained MR4.0, enter
the treatment-free remission phase. Patients will be monitored closely with
regular IS RT-Q-PCR testing.
The primary endpoint is the proportion of patients who remain in treatment-free
remission (>= MR4.0) without molecular relapse at the end of 12 months in the
treatment-free remission phase of the study. This study compares the nilotinib
12-month consolidation treatment arm (arm 1) with the nilotinib 24-month
consolidation treatment arm (arm 2) to determine the optimal duration of the
ENESTgoal study details
ENESTgoal is a US-only Phase II randomized, open-label, two arm, multicenter
study designed to determine if adults with Ph+ CML can live without drug therapy
after stopping treatment with nilotinib. Eligible patients must have been on
treatment with imatinib for at least one year and have achieved a BCR-ABL level
of less than or equal to MMR and greater than MR4.5 as measured by IS RT-Q-PCR
testing. Patients will switch to nilotinib once entering the study and will have
three years of treatment. If MR4.5 is achieved during the third year of
treatment, patients will be eligible to be randomized to either enter the
treatment-free remission phase immediately, or continue receiving nilotinib for
another year before being eligible to enter the treatment-free phase. Patients
will be monitored closely with regular IS RT-Q-PCR testing.
The primary endpoint is the percentage of patients remaining in the remission
phase (no confirmed loss of MR4.0 and no restarting of treatment with nilotinib)
at six months from the start of treatment-free phase, with no confirmed loss of
MR4.0 and no restarting of treatment with nilotinib.
About Tasigna (nilotinib)
Tasigna(®) (nilotinib) is approved in more than 90 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+, and for the treatment of adult
patients with newly diagnosed Ph+ CML in chronic phase. Take twice daily 12
hours apart. Do not take with food. No food to be consumed for 2 hours before or
one hour after dosing. Avoid grapefruit juice and CYP3A4 inhibitors.
Tasigna Important Safety Information
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. Uncommon cases (0.1 to
1%) of sudden death have been reported in clinical studies in patients with
significant risk factors.
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. Women taking Tasigna should not breastfeed.
The most frequent Grade 3 or 4 adverse events are hematological (neutropenia and
thrombocytopenia) which are generally reversible and usually managed by
withholding Tasigna temporarily or dose reduction. Monitor blood counts
regularly. Pancreatitis has been reported. The most frequent non-hematologic
adverse events were rash, pruritus, nausea, fatigue, headache, alopecia,
myalgia, constipation and diarrhea. Most of these adverse events were mild to
moderate in severity.
Please see full Prescribing Information available at www.tasigna.com.
About Glivec (imatinib)
Glivec(®) (imatinib) is approved in more than 110 countries for the treatment of
all phases of Ph+ CML, for the treatment of adult patients with KIT (CD117)-
positive gastrointestinal stromal tumors (GIST), which cannot be surgically
removed and/or have metastasized and for the treatment of adult patients
following complete surgical removal of KIT+ GIST. Take with food and a large
glass of water.
Glivec Important Safety Information
Glivec can cause fetal harm in pregnant woman. 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. Use caution in patients with
cardiac dysfunction and hepatic dysfunction. Monitor carefully.
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 and 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.
Please see full Prescribing Information available at www.glivec.com.
The foregoing release contains forward-looking statements that can be identified
by terminology such as "to evaluate," "can," "potential,"
"dedication," "ongoing," "looking to the next phase and
continues," "commitment," "planned," "will,"
"aim," "providing support," or
similar expressions, or by express or implied discussions regarding potential
new indications or labeling for Tasigna or Glivec or regarding potential future
revenues from such products . You should not place undue reliance on these
statements. Such forward-looking statements reflect the current views of
management regarding future events, and involve known and unknown risks,
uncertainties and other factors that may cause actual results with Tasigna and
Glivec to be materially different from any future results, performance or
achievements expressed or implied by such statements. There can be no guarantee
that either Tasigna or Glivec will be approved for any additional indications or
labeling in any market. Nor can there be any guarantee that Tasigna or Glivec
will achieve any particular levels of revenue in the future. In particular,
management's expectations regarding Tasigna and Glivec could be affected by,
among other things, unexpected regulatory actions or delays or government
regulation generally; unexpected clinical trial results, including unexpected
new clinical data and unexpected additional analysis of existing clinical data;
the company's ability to obtain or maintain patent or other proprietary
intellectual property protection; competition in general; government, industry
and general public pricing pressures; unexpected manufacturing issues; the
impact that the foregoing factors could have on the values attributed to the
Novartis Group's assets and liabilities as recorded in the Group's consolidated
balance sheet, and other risks and factors referred to in Novartis AG's current
Form 20-F on file with the US Securities and Exchange Commission. Should one or
more of these risks or uncertainties materialize, or should underlying
assumptions prove incorrect, actual results may vary materially from those
anticipated, believed, estimated or expected. 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.
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,
eye care, cost-saving generic pharmaceuticals, preventive vaccines and
diagnostic tools, over-the-counter and animal health products. Novartis is the
only global company with leading positions in these areas. In 2012, the Group
achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted
to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and
amortization charges). Novartis Group companies employ approximately 131,000
full-time-equivalent associates and operate in more than 140 countries around
the world. For more information, please visit www.novartis.com
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* In the Novartis treatment-free remission clinical trial program, molecular
response (reduction of BCR-ABL transcripts in the blood of patients) is measured
at four levels, based on an international standard:
* MMR (<= 0.1% BCR-ABL)
* MR4 (<= 0.01% BCR-ABL)
* MR4.5 (<= 0.0032% BCR-ABL)
* Undetectable BCR-ABL (no detectable BCR-ABL transcript level with sample
sensitivity of at least 4.5 log)
+ Known as Gleevec(® )(imatinib mesylate) tablets in the US, Canada and Israel.
1. What is World CML Day? CML Advocates Network.
2. National Comprehensive Cancer Network (NCCN): Clinical Practice Guidelines
in Oncology: Chronic Myelogenous Leukemia, V.4.2013. Available at:
3. Faderl, Stefan, et al. "The biology of chronic myeloid leukemia." New
England Journal of Medicine.1999; 341.3: 164-172.
4. Novartis data on file.
5. Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia)
Patients (ENESTFreedom). Trial identifier NCT01784068 .
. Accessed August 2013.
6. A Phase II, Single Arm, Open Label Study of Treatment-free Remission After
Achieving Sustained MR4.5 on Nilotinib (ENESTop). Trial identifier
. Accessed August 2013.
7. A Randomized Phase III Study to Assess the Effect of a Longer Duration of
Consolidation Treatment With Nilotinib on TFR in CP CML (ENESTPath). Trial
identifier NCT01743989. www.clinicaltrials.gov
. Accessed August
8. Safety and Efficacy of CML Patients Who Switch to Nilotinib and Stop
Treatment After Achieving Sustaining MR4.5. (ENESTgoal). Trial identifier
. Accessed August 2013.
# # #
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