New data at ASCO show Novartis drug Tasigna® surpasses Glivec® in slowing disease progression for newly diagnosed CML patients
(Thomson Reuters ONE) -
Novartis International AG / New data at ASCO show Novartis drug Tasigna® surpasses Glivec® in slowing disease progression for newly diagnosed CML patients processed and transmitted by Hugin AS. The issuer is solely responsible for the content of this announcement.
* 18-month median follow-up from the first head-to-head comparison of these
two oral therapies to be presented Monday, June 7 at ASCO
* In this study, Tasigna produced deeper molecular responses and significantly
reduced progression to advanced disease, resulting in fewer deaths due to
CML
* Three times more patients achieved undetectable disease at the molecular
level with Tasigna than with Glivec
* Tasigna registration data further confirmed by this new data; filing
received FDA priority review and also submitted in EU, Switzerland, Japan
Basel, June 4, 2010 - Novartis announced today 18-month results (median
follow-up) showing that Tasigna(®) (nilotinib) significantly surpasses Glivec(®)
(imatinib)* in slowing disease progression in adult patients with newly
diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in
chronic phase[1].
This 18-month median follow-up is from the first head-to-head comparison of
these two oral therapies as initial treatment for this life-threatening blood
cancer and will be presented on June 7 at the 46th American Society of Clinical
Oncology (ASCO) annual meeting in Chicago.
Tasigna produced deeper levels of molecular response than Glivec in front-line
Ph+ CML and significantly reduced progression to accelerated phase and blast
crisis, resulting in fewer deaths due to CML[1]. Notably, three times more
patients achieved undetectable disease at the molecular level with Tasigna than
with Glivec[1]. Further, Tasigna surpassed Glivec in other key measures of
treatment efficacy.
"Tasigna demonstrates that by more selectively inhibiting BCR-ABL, the key
driver of Ph+ CML, we can reduce progression to advanced disease even further
than with the current gold standard Glivec," said Richard Larson, MD, ENESTnd
study investigator and Director of the Hematologic Malignancies Program at the
University of Chicago. "The efficacy and safety findings achieved by Tasigna in
this study provide patients and physicians with an important new treatment
option."
In February 2010 the US Food & Drug Administration (FDA) granted Tasigna
priority review status for newly diagnosed Ph+ CML patients. Regulatory
submissions have been filed in the EU, Switzerland and Japan. The new ENESTnd
data to be presented at ASCO will further confirm the findings in those filings,
all of which were based on 13.8-month median follow-up data from the study.
Study details
The clinical trial, Evaluating Nilotinib Efficacy and Safety in Clinical Trials
of Newly Diagnosed Ph+ CML Patients (ENESTnd), is a Phase III randomized,
open-label, multicenter trial comparing the efficacy and safety of Tasigna
versus Glivec in adult patients with newly diagnosed Ph+ CML in chronic
phase[1]. It is the largest global randomized comparison of two oral therapies
ever conducted in newly diagnosed Ph+ CML patients.
ENESTnd is being conducted at 217 global sites with 846 patients enrolled.
Patients were randomized to receive Tasigna 300 mg twice daily (n = 282),
Tasigna 400 mg twice daily (n = 281) or Glivec 400 mg once daily (n = 283). The
primary endpoint was major molecular response (MMR) at 12 months; a secondary
endpoint was complete cytogenetic response (CCyR) by 12 months[1]. Planned
follow-up is for five years[2]. Patients on the Glivec treatment arm who had
suboptimal response or treatment failure were allowed to escalate dose and/or
switch to Tasigna via a protocol extension. The data to be presented at ASCO is
the 18-month median follow-up.
Results showed that fewer patients progressed to accelerated phase or blast
crisis on Tasigna at 300 mg twice daily (n = 2) and 400 mg twice daily (n = 1)
versus Glivec at 400 mg once daily (n = 12)[1] with 18 months of median
follow-up, demonstrating a significant improvement in disease control. The data
also showed fewer deaths due to CML on Tasigna at 300 mg twice daily (n = 2) and
400 mg twice daily (n = 1) versus Glivec at 400 mg once daily (n = 8). Rate of
MMR and CCyR remain superior for Tasigna versus Glivec at the 18-month median
follow-up.
MMR was defined in the study as reduction in the level of the abnormal BCR-ABL
gene to less than or equal to 0.1% of the pretreatment level based on an
internationally agreed standard[2]. Notably, three times more patients in the
ENESTnd study achieved undetectable disease at the molecular level (BCR-ABL
levels at 4.5-log reduction) with Tasigna than with Glivec at the 18-month
median follow-up[1]. CCyR indicates that no CML cells containing the diagnostic
Philadelphia chromosome can be seen in a sample of bone marrow taken from the
patient.
All patients had a minimum of 16 months of treatment or discontinued early; the
median follow-up was 18 months. Overall, 80%, 81% and 75% of patients remained
in the study on Tasigna 300 mg twice daily, Tasigna 400 mg twice daily and
Glivec 400 mg once daily, respectively[1].
Both Tasigna and Glivec were well tolerated overall. Rates of discontinuation
due to adverse events or laboratory abnormalities were 7% for Tasigna 300 mg
twice daily, 11% for Tasigna 400 mg twice daily, and 9% for Glivec 400 mg once
daily[1]. Fewer patients taking Tasigna discontinued due to adverse events
compared to Glivec. No patients in the study had prolongation of QT interval
/>500 milliseconds[1]. No sudden deaths occurred in any of the treatment arms[1].
About Ph+ CML
CML is a disease 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[3]. Worldwide, CML is responsible for approximately 10% to
15% of all adult cases of leukemia[4], with an incidence of one to two cases per
100,000 people per year[5].
About Tasigna[6]
Tasigna has been approved in more than 80 countries for the treatment of chronic
phase (CP) and accelerated phase Ph+ CML in adult patients resistant or
intolerant to at least one prior therapy, including Glivec. The effectiveness of
Tasigna for this indication 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.
Tasigna is not approved for the treatment of newly diagnosed Ph+ CML-CP.
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.
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
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 echocardiogram is recommended prior to initiating
therapy with Tasigna and as clinically indicated.
About Glivec[7]
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 leukemia (HES/CEL).
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.
Disclaimer
The foregoing release contains forward-looking statements that can be identified
by terminology such "priority review," "will," "can," "to be," or similar
expressions, or by express or implied discussions regarding potential new
indications or labeling for Tasigna 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 with Tasigna or Glivec 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 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 clinical
trial results, unexpected regulatory actions or delays or government regulation
generally; 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; 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.
About Novartis
Novartis 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 2009, the Group's continuing operations achieved net sales of
USD 44.3 billion, while approximately USD 7.5 billion was invested in R&D
activities throughout the Group. Headquartered in Basel, Switzerland, Novartis
Group companies employ approximately 100,000 full-time-equivalent associates and
operate in more than 140 countries around the world. For more information,
please visit http://www.novartis.com
References
[1] Larson R, le Coutre P, Reiffers J, Hughes T. et al. Nilotinib is Superior
to Imatinib in Patients (pts) with Newly Diagnosed Chronic Myeloid Leukemia in
Chronic Phase (CML-CP): ENESTnd Beyond One Year. Abstract # CRA6501. American
Society of Clinical Oncology 2010 Annual Meeting.
[2] Saglio G, Kim DW, Issaragrisil S, le Coutre P, et al. Nilotinib Demonstrates
Superior Efficacy Compared with Imatinib in Patients with Newly Diagnosed
Chronic Myeloid Leukemia in Chronic Phase: Results from the International
Randomized Phase III ENESTnd Trial. Abstract #LBA-1. American Society of
Hematology 2009 Annual Meeting.
[3] National Cancer Institute. General Information About Chronic Myelogenous
Leukemia (PDQ). Available at:
http://www.cancer.gov/cancertopics/pdq/treatment/CML/patient/. Accessed March
2009.l 1: definition of PCR. Here'
[4] American Cancer Society. Detailed Guide: CML. What are the key statistics
about CML? (Sept 2008 revision) Available at:
http://www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Are_the_Key_Statistics
_About_Chronic_Myeloid_Leukemia_CML.asp?rnav=cri. Accessed April 2009.
[5] Central European Leukemia Study Group. About CML. Available at:
http://www.cml-info.com/de/healthcare-professionals/about-cml.html. Accessed
January 2009.
[6] Tasigna (nilotinib) European Summary of Characteristics. Novartis AG.
Available at: http://www.tasigna.com/en/tasigna-product-information.jsp.
Accessed May 2010.
[7] Glivec(®) (imatinib) prescribing information. Basel, Switzerland: Novartis
International AG; March 2009.
*Known as Gleevec(®) (imatinib mesylate) tablets in the US, Canada and Israel.
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