2009-06-08 07:23:05 -
London, June , 08, 2009
Corporate news announcement processed and transmitted by Hugin AS.
The issuer is solely responsible for the content of this
announcement.
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* Afinitor significantly reduced tumor size by 50% or more in one
out of three patients with refractory or relapsed lymphoma
* Phase III study underway to explore potential of Afinitor to
prevent relapse in patients with the most common type of
non-Hodgkin's lymphoma
Basel, June 8, 2009 - New data show that Afinitor® (everolimus)
Tablets significantly shrunk tumors in 33% of patients with relapsed
non-Hodgkin's lymphoma (NHL) and Hodgkin's disease[1]. Based on
results from this study and other early-stage research, Novartis has
initiated a Phase III trial in the most common NHL, diffuse large
B-cell lymphoma (DLBCL).
Non-Hodgkin's lymphoma and Hodgkin's disease, also known as Hodgkin's
lymphoma, refer to a variety of cancers affecting the immune system,
such as DLBCL, mantle cell lymphoma and follicular lymphoma[2]. Up to
60% of patients with aggressive types of NHL, including DLBCL, may be
cured with appropriate therapy[3]. However, NHL patients have a high
risk of relapse after initial therapy and no treatments are currently
available to reduce this risk[4],[5].
The Phase II open-label trial of 145 lymphoma patients was presented
at the 14th annual European Hematology Association congress in
Berlin, Germany. Results show that 33% of patients with relapsed NHL
and Hodgkin's disease treated with everolimus experienced a 50% or
greater reduction in tumor size. This 33% overall response rate (ORR)
is defined as complete or partial tumor shrinkage (95% confidence
interval: 26-41%). The median time to disease progression for all 145
patients was 4.3 months (95% CI; 3.6-5.9 months) and the median
duration of response for the 48 responders was 6.8 months (95% CI;
5.4-11.0 months). Nineteen responders remained progression free at 6
months[1].
"We continue to see the potential of Afinitor in multiple types of
cancer," said Alessandro Riva, MD, Executive Vice President, Global
Head, Novartis Oncology Development. "These latest data show an
antitumor effect in lymphoma that support the rationale for a Phase
III study of Afinitor to prevent relapse in patients with diffuse
large B-cell lymphoma, where there is a significant unmet medical
need."
Novartis has initiated PILLAR-2 (PIvotaL Lymphoma triAls of RAD001),
a Phase III trial investigating adjuvant treatment with everolimus
(RAD001) in poor-risk patients with DLBCL who achieved complete
remission with first-line rituximab combined with chemotherapy. This
worldwide study will evaluate the potential of everolimus to extend
disease-free survival in patients with DLBCL. The longer a patient
with DLBCL is in remission the higher their likelihood to remain
disease-free. There is no approved therapy for the approximately 50%
of patients who will relapse after achieving a complete response on
initial treatment, demonstrating an important unmet need[6].
EHA study details
The proof-of-concept, open-label, single-arm, multicenter Phase II
study was designed to assess the efficacy and safety of everolimus in
patients with relapsed/refractory aggressive or indolent NHL or
Hodgkin's disease whose disease progressed despite prior treatment.
Patients had received a median of four prior therapies (between one
and 15 therapies). The study included patients with T-cell
non-Hodgkin's lymphoma, Hodgkin's disease, follicular lymphoma,
mantle cell lymphoma, DLBCL and small lymphocytic lymphoma; all of
whom had experienced disease progression despite prior treatment. The
primary endpoint of the study is to assess ORR. Secondary endpoints
include assessment of progression-free survival (PFS), overall
survival, time to disease progression and the safety profile of
Afinitor[1].
In the trial, everolimus showed anticancer activity across multiple
types of lymphoma, including T-cell non-Hodgkin's lymphoma (63% ORR),
Hodgkin's disease (53% ORR), follicular lymphoma (50% ORR), mantle
cell lymphoma (32% ORR), DLBCL (30% ORR) and small lymphocytic
lymphoma (18% ORR)[1].
Patients received everolimus 10 mg daily and were evaluated monthly.
Dose reductions to 5 mg daily and 5 mg every other day were
permitted. Response was assessed after two cycles of treatment and
periodically thereafter. Patients received a median of three
cycles[1]. Overall, everolimus was well tolerated. The most commonly
reported adverse events (grade 3 or 4; >10% patients) in this heavily
pretreated population included anemia, neutropenia and
thrombocytopenia[1].
About non-Hodgkin's lymphoma and Hodgkin's disease
Non-Hodgkin's lymphoma and Hodgkin's disease manifest in the cells of
the lymphatic system, which is composed of lymphoid tissue, lymph
vessels and lymph fluid that help the body filter out bacteria and
fight disease. Since lymphatic tissue is located throughout the body,
NHL and Hodgkin's disease can start almost anywhere[2],[7],[8]. The
most recent data indicate that more than 300,000 new cases of NHL
develop around the world each year[9].
About Afinitor
Afinitor has been approved by the US Food and Drug Administration
(FDA) as the first oral, daily therapy (5 mg and 10 mg tablets) to
treat advanced kidney cancer after failure of treatment with
sunitinib or sorafenib. Recently, the Committee for Medicinal
Products for Human Use (CHMP) issued a positive opinion supporting EU
approval of Afinitor to treat patients with advanced renal cell
carcinoma whose disease has progressed on or after treatment with
vascular endothelial growth factor (VEGF)-targeted therapy.
In cancer cells, Afinitor continuously targets mTOR, a protein that
acts as a central regulator of tumor cell division, blood vessel
growth and cell metabolism. Novartis has also filed regulatory
submissions with other regulatory agencies globally for the treatment
of advanced kidney cancer. Afinitor is being studied in multiple
cancer types, including NET, breast, gastric and hepatocellular
carcinoma (HCC), as well as tuberous sclerosis complex (TSC) and NHL.
The active ingredient in Afinitor is everolimus, which is available
in different dosage strengths under the trade name Certican® for the
prevention of organ rejection in heart and kidney transplant
recipients. Certican was first approved in the EU in 2003.
Afinitor important safety information
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.
Disclaimer
The foregoing release contains forward-looking statements that can be
identified by terminology such as "potential," "may," "risk," "will,"
"potentially," or similar expressions, or by express or implied
discussions regarding potential new marketing approvals, or new
indications or labeling for Afinitor or regarding potential future
revenues from Afinitor. 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 Afinitor to be materially different from any future results,
performance or achievements expressed or implied by such statements.
There can be no guarantee that Afinitor will be approved for sale in
any additional markets, or that Afinitor will be approved for any
additional indications or labeling. Nor can there be any guarantee
that Afinitor will achieve any particular levels of revenue in the
future. In particular, management's expectations regarding Afinitor
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; 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, preventive vaccines, diagnostic tools,
cost-saving generic pharmaceuticals 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] Thomas E. Witzig et al. A Phase II Trial of the Oral mTor
Inhibitor Everolimus in Relapsed Non-Hodgkin's Lymphoma (NHL) and
Hodgkin's Disease (HD). EHA 14th Congress. Berlin, Germany
[2] National Cancer Institute. General Information about Non-Hodgkin
Lymphoma. Available at:
www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/Hea ...
Accessed May 21,2009
[3] National Cancer Institute. What You Need to Know About
Non-Hodgkin's Lymphoma. What is Non-Hodgkin's Lymphoma? Available at:
www.cancer.gov/cancertopics/wyntk/non-hodgkin-lymphoma.
Accessed May 11,2009
[4] National Cancer Institute. General Information on Non-Hodgkin's.
Available at:
www.cancer.gov/cancertopics/pdq/treatment/adult-nonhodgkins/Heal ..
[5] National Comprehensive Cancer Network. NCCN Clinical Practice
Guidelines in Oncology: Non-Hodgkin's Lymphoma. Available at:
www.nccn.org/professionals/physician_gls/PDF/nhl.pdf. Accessed
May 11, 2009
[6] X Zhang et al. Serum diagnosis of diffuse large B-cell lymphomas
and further identification of response to therapy using SELDI-TOF-MS
and tree analysis patterning. BMC Cancer 2007, 7:235
[7] American Cancer Society. What Is Hodgkin's Disease? Available at:
www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Is_Hodgkin_Di ...
Accessed May 11, 2009
[8] National Cancer Institute. General Information About Adult
Non-Hodgkin'sLymphoma. Available at:
www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/pat ...
Accessed May 11, 2009
[9] D. Max Parkin, MD et al. Global Cancer Statistics 2002. American
Cancer Society. Available at:
www.intl-caonline.amcancersoc.org/cgi/content/full/55/2/74
Accessed May 11, 2009
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Novartis Global Media Relations Novartis Oncology
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