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
chromosome-positive 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 - Tasignaâ (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 Glivecâ (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 worldwide[1]. 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 crisis[1]. 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 cancer-causing 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.
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
Glivec-resistant 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.
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.
Disclaimer
The foregoing release contains forward-looking statements that can be
identified by terminology such as "should", "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 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.
About Novartis
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
http://www.novartis.com.
Reference
[1] Faderl S; Talpaz M; Estrov Z; O'Brien S; Kurzrock R; Kantarjian
HM. The biology of chronic myeloid leukemia. N Engl J Med.
341:164-72, 1999.
[*] Known as Gleevecâ (imatinib mesylate) tablets in the US, Canada
and Israel.
# # #
Novartis Media Relations
John Gilardi Kim Fox
Novartis Global Media Relations Novartis Oncology
+41 61 324 3018 (direct) +1 862 778 7692 (direct)
+41 79 596 1408 (mobile) kim.fox@novartis.com
john.gilardi@novartis.com
e-mail: media.relations@novartis.com
Novartis Investor Relations
International North America
Ruth Metzler-Arnold Ronen Tamir +1 212 830
Katharina Ambuehl 2433
Pierre-Michel Bringer Jill Pozarek +1 212
Jason Hannon 830 2445
Thomas Hungerbuehler Edwin Valeriano +1 212 830
Richard Jarvis 2456
Isabella Zinck
Central phone no: +41 61 324 7944
e-mail:
investor.relations@novartis.com
e-mail:
investor.relations@novartis.com
--- End of Message ---
Novartis International AG
Posfach Basel
WKN: 904278; ISIN:
CH0012005267; Index: SLCI, SMI, SPI, SLIFE;
Listed: Main Market in SWX Swiss Exchange, ZLS in BX Berne eXchange;