TasignaÂ® shows rapid and deep responses in newly diagnosed patients
with a form of chronic myeloid leukemia
TasignaÂ® shows rapid and deep responses in newly diagnosed patients
with a form of chronic myeloid leukemia
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* Phase II data demonstrate that Tasigna rapidly removes detectable
cancer cells in 96% of patients at 12 months
* At 12 months, Tasigna also achieves a rapid and deep reduction of
the abnormal protein that causes a life-threatening type of
leukemia in the majority of patients compared to historical
* Results from the Phase III head-to-head registration trial
evaluating Tasigna vs. Glivec in newly diagnosed patients are
expected in early 2010
Basel, June 5, 2009 - New data show that at 12 months newly diagnosed
patients taking TasignaÂ® (nilotinib) to treat a life-threatening form
of chronic myeloid leukemia (CML) had rapid responses and a deep
reduction in the amount of the abnormal protein that causes this
"Tasigna now demonstrates potential to achieve remarkable responses
in newly diagnosed patients," said Gianantonio Rosti, MD, Institute
of Hematology SerÃ gnoli, Bologna University, Bologna, Italy, and lead
study investigator. "These positive data suggest that, one day,
Tasigna may offer patients another front-line treatment option."
The research compared Tasigna against historical GlivecÂ® (imatinib)*
data in the treatment of patients with Philadelphia
chromosome-positive chronic myeloid leukemia (Ph+ CML). Findings were
presented today at the 14th Congress of the European Hematology
Association (EHA) in Berlin, Germany.
Traditionally with Glivec therapy, efficacy in Ph+ CML has been
measured with the objective of achieving a complete cytogenetic
response (CCyR), or reaching an undetectable level of Philadelphia
chromosome cells in a patient's bone marrow. However, through highly
sensitive measuring methods, major molecular response (MMR) has
emerged as another important measure of efficacy and may be the best
predictor of long-term progression-free survival,.
Tasigna was specifically designed to inhibit Bcr-Abl -- the abnormal
protein responsible for the uncontrolled production of white blood
cells that occurs in Ph+ CML patients -- and mutations of Bcr-Abl,
more effectively than Glivec. In this Phase II study, the time to
achieve MMR was measured as an endpoint. The data indicate that 96%
of patients taking Tasigna reached CCyR at 12 months. In this same
time period, 85% of patients taking Tasigna achieved MMR. These
data indicate a more rapid reduction in disease burden compared to
that seen in historical studies with Glivec. In this study, Tasigna
was generally well tolerated.
Results from a Phase III registration trial, ENESTnd (Evaluating
Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed
Ph+ CML Patients), evaluating Tasigna as a potential front-line
therapy for certain Ph+ CML patients, are expected in early 2010.
Currently, Tasigna is approved in more than 65 countries for the
treatment of adult patients with Ph+ CML in the chronic or
accelerated phases who are resistant or intolerant to prior
treatment, including Glivec.
The study, conducted by the Gruppo Italiano Malattie Ematologiche
dell'Adulto (GIMEMA), is an ongoing, open-label, single-stage,
multicenter Phase II clinical trial, designed to evaluate the
therapeutic efficacy and safety of Tasigna as a front-line treatment.
Seventy-three patients with newly diagnosed Ph+ CML in early chronic
phase were enrolled in the trial. After 12 months of treatment, 96%
of all patients had achieved CCyR and 85% of all patients had
Tasigna was generally well tolerated with most adverse events being
mild and moderate.
Additional research presented at EHA includes data from the
largest-ever study in the second-line CML setting, which reinforce
the efficacy and safety of Tasigna.
About Ph+ CML
CML is a disease of the blood and bone marrow 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 15% of all adult cases of leukemia, with an
incidence of one to two cases per 100,000 people per year.
Tasigna important safety information
Because taking Tasigna with food may increase the amount of drug in
the blood, Tasigna should not be taken with food and patients should
wait at least two hours after a meal before taking Tasigna. In
addition, no food should be consumed for at least one hour after the
dose is taken.
Tasigna has been approved in more than 65 countries for the treatment
of chronic phase and accelerated phase Ph+ CML in adult patients
resistant or intolerant to at least one prior therapy, including
Glivec. The effectiveness of Tasigna is based on confirmed
hematologic and unconfirmed cytogenetic response rates. There are no
controlled trials demonstrating a clinical benefit, such as
improvement in disease-related symptoms or increased survival.
The most frequent Grade 3 or 4 adverse events for Tasigna were
primarily hematological in nature and included neutropenia and
thrombocytopenia. Elevations seen in bilirubin, liver function tests,
lipase enzymes and blood sugar, were mostly transient and resolved
over time. These cases were easily managed and rarely led to
discontinuation of treatment. Pancreatitis was reported in less than
1% of cases. The most frequent non-hematologic drug-related adverse
events were rash, pruritus, nausea, fatigue, headache, constipation
and diarrhea. Most of these adverse events were mild to moderate in
Tasigna should be used with caution in patients with uncontrolled or
significant cardiac disease (e.g., recent heart attack, congestive
heart failure, unstable angina or clinically significant
bradycardia), as well as in patients who have or may develop
prolongation of QTc. These include patients with abnormally low
potassium or magnesium levels, patients with congenital long QT
syndrome, patients taking anti-arrhythmic medicines or other drugs
that may lead to QT prolongation. Low levels of potassium or
magnesium must be corrected prior to Tasigna administration. Close
monitoring for an effect on the QTc interval is advisable and a
baseline echocardiogram is recommended prior to initiating therapy
with Tasigna and as clinically indicated.
Glivec is approved in more than 90 countries including the US, EU and
Japan, for the treatment of all phases of Ph+ CML. Glivec is also
approved in the US, EU and other countries for the treatment of
patients with Kit (CD117)-positive gastrointestinal tumors (GIST),
which cannot be surgically removed and/or have already spread to
other parts of the body (metastasized). In the US and EU, Glivec is
now approved for the post-surgery treatment of adult patients
following complete surgical removal of Kit (CD117)-positive
gastrointestinal stromal tumors. In the EU, Glivec is also approved
for the treatment of adult patients with newly diagnosed Ph+ acute
lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy and
as a single agent for patients with relapsed or refractory Ph+ ALL.
Glivec is also approved for the treatment of adult patients with
unresectable, recurrent and/or metastatic dermatofibrosarcoma
protuberans (DFSP) who are not eligible for surgery. Glivec is also
approved for the treatment of patients with
myelodysplastic/myeloproliferative diseases (MDS/MPD). Glivec is also
approved for hypereosinophilic syndrome and/or chronic eosinophilic
The effectiveness of Glivec is based on overall hematological and
cytogenetic response rates and progression-free survival in CML, on
hematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, on
hematological response rates in systemic mastocytosis (SM), HES/CEL,
on objective response rates and progression-free survival in
unresectable and/or metastatic GIST, on recurrence free survival in
adjuvant GIST and on objective response rates in DFSP. Increased
survival in controlled trials has been demonstrated only in newly
diagnosed chronic phase CML and GIST.
Not all indications are available in every country.
Glivec important safety information
The majority of patients treated with Glivec in clinical trials
experienced adverse events at some time. Most events were of mild to
moderate grade and treatment discontinuation was not necessary in the
majority of cases.
The safety profile of Glivec was similar in all indications. The most
common side effects included nausea, superficial edema, muscle
cramps, skin rash, vomiting, diarrhea, abdominal pain, myalgia,
arthralgia, hemorrhage, fatigue, headache, joint pain, cough,
dizziness, dyspepsia and dyspnea, dermatitis, eczema and fluid
retention, as well as neutropenia, thrombocytopenia and anemia.
Glivec was generally well tolerated in all of the studies that were
performed, either as monotherapy or in combination with chemotherapy,
with the exception of a transient liver toxicity in the form of
transaminase elevation and hyperbilirubinemia observed when Glivec
was combined with high dose chemotherapy.
Rare/serious adverse reactions include: sepsis, pneumonia,
depression, convulsions, cardiac failure, thrombosis/embolism, ileus,
pancreatitis, hepatic failure, exfoliative dermatitis, angioedema,
Stevens-Johnson syndrome, renal failure, fluid retention, edema
(including brain, eye, pericardium, abdomen and lung), hemorrhage
(including brain, eye, kidney and gastrointestinal tract),
diverticulitis, gastrointestinal perforation, tumor
hemorrhage/necrosis and hip osteonecrosis/avascular necrosis.
Patients with cardiac disease or risk factors for cardiac failure
should be monitored carefully and any patient with signs or symptoms
consistent with cardiac failure should be evaluated and treated.
Cardiac screening should be considered in patients with HES/CEL, and
patients with MDS/MPD with high level of eosinophils (echocardiogram,
serum troponin level).
Glivec is contraindicated in patients with known hypersensitivity to
imatinib or any of its excipients. Women of childbearing potential
should be advised to avoid becoming pregnant while taking Glivec.
The foregoing release contains forward-looking statements that can be
identified by terminology such as "expected," "potential," "suggest,"
"may," "designed to evaluate," or similar expressions, or by express
or implied discussions regarding potential new indications or
labeling or potential additional marketing approvals for Tasigna or
Glivec, regarding the long-term impact of a patient's use of Tasigna
or Glivec, or regarding potential future revenues from Tasigna or
Glivec. 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 to be
materially different from any future results, performance or
achievements expressed or implied by such statements. There can be no
guarantee that Tasigna or Glivec will be approved for any additional
indications or labeling in any market, or that Tasigna will be
approved for sale in any additional markets. Neither can there be any
guarantee regarding the long-term impact of a patient's use of
Tasigna or Glivec. 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 or Glivec
could be affected by, among other things, unexpected clinical trial
results, including unexpected new clinical data and unexpected
additional analysis of existing clinical data; unexpected regulatory
actions or delays or government regulation generally; 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; 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 AG provides healthcare solutions that address the evolving
needs of patients and societies. Focused solely on healthcare,
Novartis offers a diversified portfolio to best meet these needs:
innovative medicines, cost-saving generic pharmaceuticals, preventive
vaccines, diagnostic tools and consumer health products. Novartis is
the only company with leading positions in these areas. In 2008, the
Group's continuing operations achieved net sales of USD 41.5 billion
and net income of USD 8.2 billion. Approximately USD 7.2 billion was
invested in R&D activities throughout the Group. Headquartered in
Basel, Switzerland, Novartis Group companies employ approximately
98,000 full-time-equivalent associates and operate in more than 140
countries around the world. For more information, please visit
 Rosti, G. Nilotinib 800 mg daily in early chronic phase Chronic
Myeloid Leukemia: 12-month results of a phase 2 trial of the GIMEMA
CML working party. European Society of Hematology (EHA). May 2009.
 A Study of Imatinib Versus Nilotinib in Adult Patients With a
Suboptimal Cytogenetic Response With Philadelphia Chromosome Positive
(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) (ENEST).
Accessed April 2009.
 Iacobucci I., Saglio, G., Rosti, G., et al. Achieving a Major
Molecular Response at the Time of a Complete Cytogenetic Response
(CCgR) Predicts a Better Duration of CCgR in Imatinib-Treated Chronic
Myeloid Leukemia Patients Clin Cancer Res 2006;12 (10) May 15, 2006.
 Ross, D., et. al. Limited clinical value of regular bone marrow
cytogenic analysis in imatinib-treated chronic phase CML patients
monitored by RQ-PCR for BCR-ABL.
Accessed March 2009.
 Tasigna (nilotinib) Prescribing Information. East Hanover, New
Jersey, USA: Novartis Pharma.
 Nicolini, F.E. Final safety analysis of 1,793 CML patients from
ENACT (Expanding Nilotinib Access in Clinical Trials) study in adult
patients with imatinib-resistant or -intolerant chronic myeloid
leukemia (CML). European Society of Hematology (EHA). May 2009.
Abstract # 0630.
 National Cancer Institute. General Information About Chronic
Myelogenous Leukemia (PDQ).
Accessed March 2009.
 American Cancer Society. Detailed Guide: CML. What are the key
statistics about CML? (Sept 2008 revision) Available at:
Myeloid_Leukemia_CML.asp?rnav=cri. Accessed April 2009.
 Central European Leukemia Study Group. About CML. [Cited 2009 Jan
13] Available from:
*Known as GleevecÂ® (imatinib mesylate) tablets in the US, Canada and
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