2009-05-28 07:27:02 -
London, May , 28, 2009
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* Oral presentation on Sandostatin® LAR® Phase III data shows
significant antitumor benefit in patients with advanced
neuroendocrine tumors of the midgut
* Early data show that at eight weeks of treatment, Afinitor®
stabilized or reduced tumor size in 61% of patients with advanced
liver cancer
* New data reveal postmenopausal women with breast cancer taking
Femara® experience better cognitive function than those taking
tamoxifen
* Phase II data show potential of Glivec® in treating patients with
advanced KIT-mutated melanoma; other Novartis data on advanced
melanoma also presented
Basel, May 28, 2009 - Novartis announced today that data on more than
15 compounds in its robust oncology portfolio will be included at the
2009 American Society of Clinical Oncology (ASCO) annual meeting.
These studies provide new research on multiple tumor types and rare
cancers.
"Our strong presence at ASCO showcases our continued progress in
developing innovative therapies for patients with cancer through our
comprehensive discovery and development program," said David Epstein,
President and CEO, Novartis Oncology, Novartis Molecular Diagnostics.
"We look forward to continuing to explore novel ways to help patients
in need of new treatments."
Sandostatin LAR in metastatic neuroendocrine midgut tumors
Data from the PROMID study (abstract #4508) show Sandostatin® LAR®
(octreotide acetate for injectable suspension) demonstrated a
significant antitumor effect in patients with metastatic
neuroendocrine tumors (NET) of the midgut[1].
Sandostatin LAR, when compared to placebo, more than doubled time
without tumor growth (15.6 months vs. 5.9 months) and reduced the
risk of disease progression by 67% (hazard ratio=0.33 with 95%
confidence interval 0.19 to 0.55; P=0.000017)[1].
This important benefit was seen in patients with functioning tumors
(i.e., tumors that are associated with carcinoid syndrome due to the
secretion of various hormones that cause symptoms, such as diarrhea
or flushing) and non-functioning (non-secreting) tumors. In an
analysis of patients with non-functioning tumors, which affect the
majority of people with NET, time to tumor progression for patients
receiving Sandostatin LAR was 27.14 months versus 7.21 months for
those on placebo (P=0.0008)[1].
Further, a statistically significant benefit was observed in patients
with tumor load <=10%, which suggests a potentially important role
for treatment in the early stages of the disease. The median time to
tumor progression was 27.1 months in the patients receiving
Sandostatin LAR versus 7.2 months in the placebo group (P<0.0001)[1].
The trial, called PROMID (Placebo-controlled prospective Randomized
study on the antiproliferative efficacy of Octreotide LAR in patients
with metastatic neuroendocrine MIDgut tumors), is a Phase IIIb study
conducted at 18 sites in Germany to evaluate the antitumor effect of
Sandostatin LAR in patients with midgut NET. The study included 85
patients who were treated with either Sandostatin LAR (30 mg/month)
or placebo for 18 months, or until tumor progression or death. All
patients in the study were treatment-naïve, had locally inoperable or
metastatic NET with the primary tumor located in the midgut, were
without curative therapeutic options and had tumors that were either
functioning or non-functioning. Interim results from PROMID were
presented at the 2009 ASCO Gastrointestinal Cancer Symposium[1].
Neuroendocrine tumors originate from cells that have roles both in
the endocrine and nervous systems. While these NET are often
slow-growing, when the tumor is inoperable patients with advanced NET
have limited treatment options[2].
The safety findings observed in the PROMID study were consistent with
those seen in previous studies of Sandostatin LAR in patients with
NET. The most frequently observed serious adverse events affected the
gastrointestinal tract, hematopoietic system and other general
symptoms such as fatigue and fever[1].
Afinitor in patients with advanced liver cancer
Phase I data (abstract #4587) demonstrated that 61% of patients with
advanced hepatocellular carcinoma (HCC) who received daily treatment
with Afinitor® (everolimus) Tablets had tumors that stabilized or
reduced in size[3].
There are currently a limited number of treatment options for
patients with advanced HCC, the stage when most are diagnosed[4],[5].
Everolimus shows potential to help address this unmet medical
need[1].
The trial, conducted in Taiwan by Dr Li-Tzong Chen from the National
Health Research Institute, included 36 advanced HCC patients who
progressed after various systemic therapies or who were no longer
candidates for local therapies, including surgery, percutaneous
ablation or transcatheter arterial chemoembolization. Of the 31
patients evaluable in the trial, 16 received everolimus (known as
RAD001 in this study) daily. The study objective was to define the
maximum tolerated dose and pharmacokinetics of everolimus[3].
The Grade 3 and 4 adverse events reported in the study included
elevated bilirubin, drop in platelets count, diarrhea, bleeding,
cardiac ischemia, elevated liver function tests and infection.
Reactivation of Hepatitis B virus was observed in four patients as
well as reactivation of Hepatitis C virus in one patient[3].
Based on these data, a global Phase III clinical trial to study the
daily everolimus regimen in patients with advanced HCC is in
development by Novartis.
Femara BIG 1-98 data on cognitive function
Impaired cognition is a concern among breast cancer patients taking
hormonal therapies. Estrogen is believed to have a direct influence
on cognitive function. Aromatase inhibitors reduce the level of
circulating estrogen in the body. It has been suggested that reduced
estrogen in the body is linked to a decline in cognitive function[6].
A new substudy (abstract #510) conducted within a subgroup of
patients enrolled in the independent Breast International Group (BIG)
1-98 study (Femara® [letrozole] vs. tamoxifen) found that
postmenopausal women with hormone receptor-positive early breast
cancer taking adjuvant Femara had better overall cognitive function
than those taking tamoxifen, based on validated scales of cognitive
function collected at the fifth year of endocrine treatment[6].
Results from this study revealed that the group of patients receiving
Femara had clinically and significantly better overall cognitive
function than the patients in the tamoxifen group (difference in mean
composite scores =0.23, P=0.04, 95% CI: 0.02-0.54). Overall, both
groups performed below age norms on most domains[6].
Highlights in melanoma
New data highlight the potential of two Novartis products as
treatments for advanced melanoma, the most serious form of skin
cancer. Melanoma accounts for 41,000 deaths worldwide each
year[7],[8]. While melanoma is curable when diagnosed and treated in
early stages, advanced melanoma is often resistant to currently
available treatments[9].
New data from a Phase II study (abstract #9001) show the potential of
Glivec®# (imatinib) in treating patients with advanced melanoma
harboring KIT mutations. A mutation in the protein called KIT,
located on the surface of normal cells, signals cells to continually
grow and divide. Similar KIT mutations in GIST were shown to be
treated effectively by Glivec. The preliminary data from the
investigator-driven study show that five out of five patients
evaluable for responses showed either partial responses to Glivec (3
out of 5) or stable disease (2 out of 5). Responses in two of the
three patients are ongoing past 18 weeks. These favorable results
have allowed the study to continue to a second expanded stage of
enrollment[10].
Other data on advanced melanoma include preliminary results from a
Phase II trial (abstract #9027) that show 72% of patients (20 out of
28) with advanced melanoma treated with everolimus in combination
with bevacizumab experienced a clinical benefit (4% had a partial
response and 68% had stable disease). The combination of everolimus
and bevacizumab was generally well tolerated. According to the
abstract, one patient withdrew from the trial due to interstitial
pneumonitis, which was reversible, and one patient had a fatal heart
attack, possibly bevacizumab-related. Grade 3 mucositis occurred in
13% of patients and all other grade 3 toxicities occurred in <10% of
patients[11].
Early stage development data
* Abstract #8542: Panobinostat + lenalidomide and dexamethasone
Phase I trial in multiple myeloma (MM)
* In this first Phase I clinical trial assessing the
combination of panobinostat (LBH589) in combination with
lenalidomide and dexamethasone, the 5 mg and 10 mg doses of
panobinostat were safe when administered to patients with
multiple myeloma[12].
* Abstract #3563: TKI258 (dovitinib lactate) in metastatic renal
cell carcinoma (mRCC) patients refractory to approved targeted
therapies: a Phase I/II dose finding and biomarker study
* This study of heavily pre-treated metastatic renal cell
carcinoma patients demonstrated that TKI258 500 mg/day may
be an appropriate dosing schedule and showed clinical
benefit in this patient population[13].
* Abstract #3533: Pharmacodynamics and pharmacokinetics of AUY922
in a Phase I study of solid tumor patients
* These data support the use of HSP70 as a biomarker for HSP90
inhibition. Inhibition of HSP90, a key target that regulates
tumor cell survival and division, through the use of AUY922,
resulted in an up regulation/increase of HSP70. The change
in HSP70 observed at the highest dose of AUY922 exceeded the
level needed to inhibit tumor growth in a mouse model for
breast cancer[14].
About the Novartis Oncology pipeline
The Novartis Oncology pipeline features 18 new molecular entities.
These compounds are being studied in more than 40 different cancer
types in approximately 15,000 patients. The pipeline portfolio
encompasses a broad array of therapeutic strategies for fighting
cancer, including novel targeted agents, monoclonal antibodies,
deacetylase (DAC) inhibitors, multiligand somatostatin analogs and
novel cytotoxics.
Sandostatin LAR important safety information
Sandostatin LAR is a long-acting, injectable depot formulation of
octreotide acetate that is indicated for the treatment of acromegaly;
for patients in whom surgery or radiotherapy is inappropriate or
ineffective; for patients until radiotherapy becomes fully effective;
and for the relief of symptoms associated with functional GEP-NET.
Octreotide has been used to treat the clinical syndromes associated
with NET and substantially reduces, and in many cases can control,
growth hormone and/or normalize IGF-1 levels in patients with
acromegaly, a disease caused by a GH-secreting pituitary adenoma.
Patients who have a known hypersensitivity to octreotide or to any of
the excipients should not take Sandostatin LAR. Dose adjustments of
drugs, such as beta-blockers, calcium channel blockers or agents to
control fluid and electrolyte balance may be necessary. Caution
should be used in patients with insulinomas; patients with diabetes
mellitus thyroid function should be monitored if receiving prolonged
treatment with octreotide. Patients receiving Sandostatin LAR should
receive periodic examination of the gallbladder; and patients who
have a history of vitamin B12 deprivation should have their vitamin
B12 levels monitored. Caution should be used in patients with
pregnancy; patients should be advised to use adequate contraception,
if necessary. Patients should not breast-feed during Sandostatin LAR
treatment. The use of Sandostatin LAR may increase the
bioavailability of bromocriptine, impair intestinal absorption of
cyclosporin and delay that of cimetidine. Drugs mainly metabolized by
CYP3A4 and that have a low therapeutic index should be used with
caution.
The most common (>= 1/10) adverse drug reactions in clinical studies
with Sandostatin LAR were diarrhea, abdominal pain, nausea,
constipation, flatulence, headache, cholelithiasis, hyperglycemia and
injection-site localized pain. Common (>= 1/100, < 1/10) adverse drug
reactions were dyspepsia, vomiting, abdominal bloating, steatorrhea,
loose stools, discoloration of feces, dizziness, hypothyroidism,
thyroid dysfunction (e.g., decreased thyroid stimulating hormone,
decreased Total T4 and decreased Free T4), cholecystitis, biliary
sludge, hyperbilirubinemia, hypoglycemia, impairment of glucose
tolerance, anorexia, elevated transaminase levels, pruritus, rash,
alopecia, dyspnea and bradycardia.
The uncommon (>= 1/1000, <1/100) adverse drug reactions were
dehydration and tachycardia. The following adverse reactions have
been reported postmarketing: anaphylaxis, allergy/hypersensitivity
reactions, urticaria, acute pancreatitis, acute hepatitis without
cholestasis, cholestatic hepatitis, cholestasis, jaundice,
cholestatic jaundice, arrhythmia, increased alkaline phosphatase
levels and increased gamma glutamyl transferase levels.
Afinitor important safety information
Afinitor is approved in the US as the first oral, daily therapy (5 mg
and 10 mg tablets) to treat patients with advanced renal cell
carcinoma after failure of treatment with sunitinib or sorafenib.
Afinitor is contraindicated in patients with hypersensitivity to
everolimus, to other rapamycin derivatives or to any of the
excipients. Potentially serious adverse reactions include
non-infectious pneumonitis and infections for which patients should
be monitored carefully and treated as needed. In addition,
non-infectious pneumonitis may require temporary dose reduction
and/or interruption or discontinuation. Patients with systemic
invasive fungal infections should not receive Afinitor. Oral
ulceration is a common side effect with Afinitor. Renal function,
blood glucose, lipids and hematological parameters should be
evaluated prior to the start of therapy with Afinitor and
periodically thereafter. Strong or moderate CYP3A4 or P-glycoprotein
inhibitors should be avoided. An increase in the dose of Afinitor is
recommended when co-administered with a strong CYP3A4 inducer. Live
vaccinations and close contact with those who have received live
vaccines should be avoided by patients taking Afinitor. Afinitor
should not be used in patients with severe hepatic impairment.
Afinitor may cause fetal harm in pregnant women.
The most common adverse reactions irrespective of causality
(incidence >=30%) were stomatitis, infections, asthenia, fatigue,
cough and diarrhea. The most common grade 3/4 adverse reactions
irrespective of causality (incidence >=3%) were infections, dyspnea,
fatigue, stomatitis, dehydration, pneumonitis, abdominal pain and
asthenia. The most common laboratory abnormalities (incidence >=50%)
were anemia, hypercholesterolemia, hypertriglyceridemia,
hyperglycemia, lymphopenia and increased creatinine. The most common
grade 3/4 laboratory abnormalities (incidence >=3%) were lymphopenia,
hyperglycemia, anemia, hypophosphatemia and hypercholesterolemia.
Deaths due to acute respiratory failure (0.7%), infection (0.7%) and
acute renal failure (0.4%) were observed in patients receiving
Afinitor.
Femara important safety information
Femara should not be taken by women who have previously had any
unusual or allergic reactions to letrozole or any of its ingredients.
Femara should not be taken by women who are pregnant or
breastfeeding. Only women who are of postmenopausal endocrine status
should take Femara. Patients with severe liver impairment should be
monitored closely. The use of Femara in patients with significantly
impaired kidney function warrants careful consideration.
The most common side effects of Femara are hot flushes, fatigue,
joint pain and nausea. Other common side effects are anorexia,
appetite increase, peripheral edema, headache, dizziness, vomiting,
dyspepsia, constipation, diarrhea, hair loss, increased sweating,
rash, muscle pain, bone pain, arthritis, osteoporosis, bone
fractures, weight increase, hypercholesterolemia and depression.
Other rare, but potentially serious adverse events include
leukopenia, cataract, cerebrovascular accident or infarction,
thrombophlebitis, pulmonary embolism, arterial thrombosis and
ischemic cardiovascular disease.
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 as "progress toward," "potential,"
"will," "look forward to," "risk," "suggests," "potentially," "in
development," "may," "pipeline," "being studied," "strategies," or
similar expressions, or by express or implied discussions regarding
potential future marketing approvals for compounds in development,
potential new indications or labeling for existing products, or
regarding potential future revenues from such compounds or products.
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 any such development compounds will be approved for
sale in any market. Nor can there be any guarantee that any of the
existing products referred to in this release will be approved for
any additional indications or labeling in any market. Neither can
there be any guarantee that any of these compounds or products will
achieve any particular levels of revenue in the future. In
particular, management's expectations regarding compounds and
products 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.
About Novartis
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
www.novartis.com.
References
[1] Arnold R, et al. Placebo-controlled, double-blind, prospective,
randomized study of the effect of octreotide LAR in the control of
tumor growth in patients with metastatic neuroendocrine midgut
tumors: A report from the PROMID study group. Abstract # 4508.
American Society of Clinical Oncology 2009 Annual Meeting, Orlando,
FL.
[2] Kloppel G, Perren A, Heitz PU The Gastroenteropancreatic
Neuroendocrine Cell System and Its Tumors: The WHO Classification.
Ann. of the New York Acad of Sci. 2006 Jan 16 2005;1014:13-27.
[3] Chen L, et al. Randomized, phase I, and pharmacokinetic (PK)
study of RAD001, an mTOR inhibitor, in patients (pts) with advanced
hepatocellular carcinoma (HCC). Abstract # 4587. American Society of
Clinical Oncology 2009 Annual Meeting, Orlando, FL. Abstract #510.
American Society of Clinical Oncology 2009 Annual Meeting, Orlando,
FL.
[4] American Cancer Society. How is Liver Cancer Treated? Available
at:
www.cancer.org/docroot/CRI/content/CRI_2_2_4X_How_Is_Liver_Cance ...
Accessed April 2009.
[5] American Cancer Society. How is Liver Cancer Staged? Available
at:
www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_liver_cance ...
Accessed May 2009.
[6] Ribi K, et al. Cognitive function in postmenopausal women
receiving adjuvant letrozole or tamoxifen in the Breast International
Group (BIG) 1-98 trial. Abstract # 510. American Society of Clinical
Oncology 2009 Annual Meeting, Orlando, FL.
[7] Skin Cancer Foundation. Understanding Melanoma. Available at:
www.skincancer.org/melanoma/. Accessed May 2009.
[8] D. Max Parkin, MD et al. Global Cancer Statistics 2002. American
Cancer Society. Available at:
caonline.amcancersoc.org/cgi/reprint/55/2/74. Accessed May 21,
2009
[9] National Cancer institute. Recurrent Melanoma. Available at:
www.cancer.gov/cancertopics/pdq/treatment/melanoma/HealthProfess ...
Accessed May 2009.
[10] Carvajal RD, et al. A phase II study of Imatinib mesylate (IM)
for patients with advanced melanoma harboring somatic alterations of
KIT. Abstract # 9001. American Society of Clinical Oncology 2009
Annual Meeting, Orlando, FL.
[11] Hainsworth J et al. Phase II trial of bevacizumab and everolimus
in the treatment of patients with metastatic melanoma: Preliminary
results. Abstract # 9027. American Society of Clinical Oncology 2009
Annual Meeting, Orlando, FL.
[12] Spencer A, et al. Panobinostat + lenalidomide and dexamethasone
Phase I trial in multiple myeloma (MM). Abstract #8542. American
Society of Clinical Oncology 2009 Annual Meeting, Orlando, FL.
[13] Angevin E, et al. TKI258 (dovitinib lactate) in metastatic renal
cell carcinoma (mRCC) patients refractory to approved targeted
therapies: a phase I/II dose finding and biomarker study. Abstract
#3563. American Society of Clinical Oncology 2009 Annual Meeting,
Orlando, FL.
[14]Ide S, et al. Pharmacodynamics and pharmacokinetics of AUY922 in
a phase I study of solid tumor patients. Abstract #3533. American
Society of Clinical Oncology 2009 Annual Meeting, Orlando, FL.
* Updated data from these abstracts may be presented at the ASCO
annual meeting
# Known as Gleevec® (imatinib mesylate) tablets in the US, Canada and
Israel
# # #
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