Novartis International AG
Novartis Global Communications
CH-4002 Basel
Switzerland
http://www.novartis.com
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MEDIA RELEASE •
Tasigna® gains European approval for patients with a life-threatening
form of leukemia who are resistant or intolerant to existing therapies
• Tasigna produced response in 49% of patients with Philadelphia chromosomepositive
chronic myeloid leukemia resistant or intolerant to existing therapies
• Phase III trials launched to explore potential of Tasigna in newly diagnosed CML
patients and also those with sub-optimal response to prior treatment
Basel, November 28, 2007 – Tasigna® (nilotinib) has received European Union approval as
a new anti-cancer therapy for patients with a life-threatening form of leukemia who are
resistant or intolerant to prior treatment including Glivec® (imatinib)*.
The EU approval was supported by data showing that Tasigna produced a positive
response in 49% of patients in the chronic phase of Philadelphia chromosome-positive
(Ph+) chronic myeloid leukemia (CML). Most patients achieved this response within three
months of starting Tasigna treatment.
“The approval of Tasigna gives us the opportunity to help more CML patients and, with
Glivec as our first line agent, provide comprehensive treatment options for prescribers,”
said David Epstein, President and CEO of Novartis Oncology. “Tasigna drives home our
commitment to develop compounds to fulfill unmet medical needs by pursuing indications
for patients with limited treatment options.”
The European Commission decision applies in all 27 EU member states plus Norway and
Iceland, and follows recent approvals in the US and Switzerland. Tasigna is now approved
in a total of 37 countries, and was also submitted for approval in Japan in June.
CML is one of the four most common types of leukemia, responsible for about 15% of all
leukemia cases worldwide1. Without treatment, CML typically progresses over three to five
years from the initial (chronic) phase through a transition (accelerated) phase to a rapidly
fatal form called blast crisis1. Tasigna is indicated in the EU for the treatment of adults who
are in chronic or accelerated phase Ph+ CML and have resistance or intolerance to prior
therapy including Glivec.
Taken twice daily, Tasigna works by inhibiting the proliferation of cells containing an
abnormal chromosome in patients with CML. 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 driver of the overproduction of cancercausing
white blood cells in patients with Ph+ CML.
Tasigna was designed to target the Bcr-Abl protein more preferentially than Glivec without
adding new mechanisms of action.
* Known as Gleevec® (imatinib mesylate) tablets in the US, Canada and Israel.
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Earlier this year, a Phase III clinical trial program was launched to compare Tasigna with
Glivec for the treatment of newly diagnosed patients with chronic phase Ph+ CML. A study
is also underway comparing these two targeted therapies in chronic phase Ph+ CML
patients who had sub-optimal responses to previous therapy. Separately, a Phase III
program has been launched involving the use of Tasigna in patients with gastrointestinal
stromal tumors (GIST) who are resistant or intolerant to prior treatment.
The EU approval of Tasigna was based on a pivotal clinical trial evaluating the rates of
cytogenetic response (i.e. reduction or elimination of the Philadelphia chromosome) and
confirmed hematologic response (i.e. normalization of white blood cell counts) in Glivecresistant
or -intolerant patients with Ph+ CML in chronic and accelerated phase.
The major cytogenetic response rate with Tasigna was 49% for chronic phase patients and
27% for accelerated phase patients. The complete hematologic response rate was 70% for
chronic phase patients who were not already in complete hematologic response at the start
of the trial, and the confirmed hematologic response rate was 42% for accelerated phase
patients.
The US Food and Drug Administration (FDA) approved Tasigna in October 2007 based on
the same pivotal clinical trial that supported the EU filing, but using a different analysis
(including shorter duration of follow-up) that produced slightly different response rates.
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 myeloid leukemia in adult
patients resistant or intolerant to at least one prior therapy including Glivec. The
effectiveness of Tasigna is based on confirmed 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 severity.
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 ECG is recommended prior to initiating therapy with
Tasigna and as clinically indicated.
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About Glivec
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 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, 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.
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