Tasigna® receives US approval providing new hope to chronic myeloid
leukemia patients with resistance or intolerance to existing
* Tasigna produced responses in 40% of patients with Philadelphia
chromosome-positive chronic myeloid leukemia resistant or
intolerant to prior treatment
* Approval and availability in US means Novartis can offer physicians
and patients a comprehensive treatment approach for this disease
Basel, October 29, 2007 - Tasigna® (nilotinib) has been approved in
the US as a new anti-cancer therapy for certain patients with a
life-threatening form of leukemia who are resistant or intolerant to
prior treatment including Glivec® (imatinib)*, an established
treatment standard and a leading Novartis medicine.
Novartis will make Tasigna available throughout the US within days
following this approval by the Food and Drug Administration (FDA) to
meet the treatment needs of these patients with Philadelphia
chromosome-positive (Ph+) chronic myeloid leukemia (CML).
CML is one of the four most common types of leukemia, a form of blood
cancer, and affects around 4,500 people in the US each year.
"Tasigna represents an important advance for the small number of
patients who are resistant or intolerant to prior therapy," said
David Epstein, President and CEO of Novartis Oncology. "This approval
means we can offer physicians a comprehensive treatment approach with
effective medicines to treat their Ph+ CML patients."
Taken twice daily, Tasigna works by inhibiting the proliferation of
cells containing an abnormal chromosome. It does this by targeting
the production of the Bcr-Abl protein, which is produced only by
cells containing the abnormal Philadelphia chromosome. This protein
is recognized as the key cause and driver of the overproduction of
cancer-causing white blood cells in patients with Ph+ CML.
Tasigna was specifically designed to target the Bcr-Abl protein more
preferentially than Glivec without adding new mechanisms of action.
At six months follow-up, Tasigna reduced or eliminated cells carrying
the abnormal Philadelphia chromosome in 40% of patients in chronic
phase of the disease.
Applying experience gained from the development of Glivec, which
remains the most frequently prescribed treatment for patients with
CML, a team of Novartis scientists created Tasigna in August 2002,
just a year after the launch of Glivec. In preclinical studies, the
medicine was able to overcome resistance resulting from Bcr-Abl
kinase mutations in 32 of 33 cell lines commonly associated with Ph+
CML. Patients with a variety of these mutations also responded to
treatment with Tasigna.
The first worldwide approval for Tasigna came in Switzerland in July
2007. European Union approval is expected by the end of this year
after the Committee for Medicinal Products for Human Use (CHMP),
which reviews medicines in Europe, issued a positive opinion in
September. Tasigna was also submitted for approval in Japan in June.
Without treatment, CML typically progresses over three to five years
from the initial (chronic) phase through a transition period
(accelerated phase) to a rapidly fatal form (blast crisis). Recent
landmark clinical trial results for Glivec show that nearly 90% of
newly diagnosed chronic-phase Ph+ CML adult patients treated with
Glivec were alive after five years, but some develop resistance or
cannot tolerate this therapy.
The FDA approved Tasigna for treatment of chronic-phase and
accelerated-phase Ph+ CML in adult patients resistant or intolerant
to prior treatment, that included Glivec. This approval is based on
an open-label multicenter clinical trial evaluating the drug's safety
and rates of cytogenetic response (i.e. reduction or elimination of
the Philadelphia chromosome) and hematologic response (i.e.
normalization of white blood cell counts) in Glivec-resistant or
-intolerant patients with Ph+ CML in chronic phase (n=280) and
accelerated phase (n=105).
In clinical trials, the primary endpoint for patients in chronic
phase was unconfirmed major cytogenetic response (MCyR). After a
minimum follow-up of six months (median treatment duration 8.7
months), Tasigna produced MCyR in 40% of 232 chronic phase patients
evaluated for efficacy. The complete cytogenetic response in these
patients was 28%.
For patients in accelerated phase, the primary endpoint was confirmed
hematological response (HR). Complete HR was reported in 18% of
patients in accelerated phase. (Accelerated phase patients had a
minimum follow-up of four months and a median treatment duration of
The highest prior Glivec dose was at least 600 mg/day in 77% of
patients, with 44% of patients receiving doses of 800 mg/day or
higher. In addition, 24 different mutations in Bcr-Abl were noted in
19% of chronic phase and 25% of accelerated phase CML patients who
were evaluated for mutations.
Tasigna 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.
In countries where it is approved, Tasigna is indicated for the
treatment of chronic phase and accelerated phase Philadelphia
chromosome-positive chronic myelogenous leukemia in adult patients
resistant or intolerant to at least one prior therapy including
Glivec. The effectiveness of Tasigna is based on hematologic and
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 were seen in bilirubin, liver function
tests, lipase enzymes and blood sugar, which were mostly transient
and resolved over time. These cases were easily managed and rarely
led to discontinuation. 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.
Studies have also shown virtually no non-hematologic
cross-intolerance between Glivec and Tasigna. (Cross-intolerance
occurs when patients cannot tolerate two different drugs because of
the same side effects). Causes of non-hematologic intolerance to
Glivec included Grade 3 or 4 rash/skin toxicity, fluid retention,
gastrointestinal intolerance, liver toxicity, and myalgia/arthralgia.
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 EU, US 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 Japan, Glivec is approved
for the treatment of patients with Kit (CD117)-positive GIST. 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 leukemia (HES/CEL).
The effectiveness of Glivec is based on overall hematologic and
cytogenetic response rates and progression-free survival in CML, on
hematological and cytogenetic response rates in Ph+ ALL, and on
objective response rates in GIST and DFSP. There are no controlled
trials demonstrating increased survival. Not all indications are
available in every country.
Glivec contraindications, warnings and adverse events
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, fluid
retention, as well as neutropenia, thrombocytopenia and anemia.
Glivec was generally well-tolerated in all 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, 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 "will," "should," "can,"
"expected," "may" or similar expressions, or by express or implied
discussions regarding potential regulatory approvals, new indications
or labeling for, or potential future sales of, Glivec or Tasigna.
Such forward-looking statements reflect the current views of Novartis
regarding future events, and involve known and unknown risks,
uncertainties and other factors that may cause actual results with
Glivec or Tasigna to be materially different from any future results,
performance or achievements expressed or implied by such statements.
There can be no guarantee that Tasigna will be approved in the EU,
Japan or any additional market; that that Glivec or Tasigna will be
approved for any additional indications or labelling in any market;
or that Glivec or Tasigna will reach any particular level of sales.
In particular, management's expectations regarding Glivec or Tasigna
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; Novartis'
ability to obtain or maintain patent or other proprietary
intellectual property protection; unexpected delays due to
manufacturing; competition in general; government, industry and
general public pricing pressures, and other risks and factors
referred to in Novartis AG's current Form 20-F on file with the U.S.
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 (NYSE: NVS) is a world leader in offering medicines to
protect health, cure disease and improve well-being. Our goal is to
discover, develop and successfully market innovative products to
treat patients, ease suffering and enhance the quality of life. We
are strengthening our medicine-based portfolio, which is focused on
strategic growth platforms in innovation-driven pharmaceuticals,
high-quality and low-cost generics, human vaccines and leading
self-medication OTC brands. Novartis is the only company with
leadership positions in these areas. In 2006, the Group's businesses
achieved net sales of USD 37.0 billion and net income of USD 7.2
billion. Approximately USD 5.4 billion was invested in R&D.
Headquartered in Basel, Switzerland, Novartis Group companies employ
approximately 100,000 associates and operate in over 140 countries
around the world. For more information, please visit
1. American Cancer Society. Overview: Leukemia - Chronic Myeloid
Last accessed October, 2007.
2. Faderl S; Talpaz M; Estrov Z; O'Brien S; Kurzrock R;
Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med.
3. Druker, B. et al. Five-Year Follow-up of Patients Receiving
Imatinib for Chronic Myeloid Leukemia. N Engl J Med 2006;355:2408-17.
* Known as Gleevec® (imatinib mesylate) in the US, Canada and Israel.
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