RAD001 Shows Potential to Reverse Resistance to Herceptin(R)* in Metastatic Breast Cancer Patients, Leading to Phase III Trial
clinical studies show that RAD001(R) (everolimus) may overcome resistance to
Herceptin(R) (trastuzumab)* in women with HER2-positive metastatic breast
cancer. These results support the initiation of a Phase III clinical trial
program to fully explore the potential of RAD001 (proposed brand name
Afinitor(R)) in breast cancer.
Two Phase I studies were presented today during the CTRC-AACR San Antonio
Breast Cancer Symposium. Initial results from both studies were released
earlier this year at the American Society of Clinical Oncology (ASCO) annual
meeting.
Updated results from the first Phase I trial show that the combination of
RAD001 with Herceptin and weekly Taxol(R) (paclitaxel)** halted tumor growth
in 77% of patients with HER2-positive metastatic breast cancer with documented
resistance to Herceptin. In addition, the data demonstrated the first complete
response in the trial.
In addition, updated data from the second Phase I study show promising
anticancer activity for RAD001 in combination with Herceptin and Navelbine(R)
(vinorelbine)*** in heavily pretreated Herceptin-resistant patients with
HER2-positive metastatic breast cancer. In the study, RAD001 in combination
with Herceptin and Navelbine halted tumor growth in 62% of patients.
“Data presented at this meeting affirm the potential of RAD001 to reverse
Herceptin resistance and restore patient response to treatment,” said
O’Regan
are important for patients with HER2-positive metastatic breast cancer who
develop resistance to Herceptin.”
Preclinical data have shown that RAD001, an inhibitor of mTOR, acts on the
pathway that mediates Herceptin resistance and has the potential to help
restore response in these patients. RAD001 works through direct antitumor
activity and through its influence on two of the most important pathways for
breast cancer, the erbB receptor and the HER2 pathways.
“We are encouraged by the benefit RAD001 provided to advanced breast
cancer patients in these early trials,” said
Vice President & Global Head of Development, Novartis Oncology. “Novartis is
committed to further evaluating the potential of RAD001 in combination with
Herceptin as a new treatment regimen in breast cancer, as well as studying its
role in treating other tumor types.”
Novartis will initiate a worldwide Phase III clinical trial program to
further evaluate the potential of RAD001 in combination with Herceptin and
chemotherapy in patients with HER2-positive metastatic breast cancer. To learn
more about the trial, please visit http://mail.breastcancerresearchstudy.com/,
or speak to your doctor.
Study details: abstract #3119
An open-label, multicenter Phase I dose escalation trial evaluated daily
RAD001 (5 mg, 10 mg) and weekly RAD001 (30 mg, 50 mg and 70 mg) regimens in
combination with Taxol (80 mg/m2 IV over 60 min on days 1, 8 and 15 every 28
days) and Herceptin (2 mg/kg IV over 30 min) in heavily pretreated patients
with HER2-positive metastatic breast cancer with prior resistance to
Herceptin.
Across treatment arms, there was an overall disease control rate of 77%
(complete response/ partial response/ stable disease greater than or equal to
16 weeks). Twenty-two heavily pretreated patients were evaluable for efficacy:
treatment arms included five patients assigned to RAD001 5 mg daily, eight to
RAD001 10 mg daily and nine to RAD001 30 mg weekly. Among the five patients
evaluated in the 5 mg daily treatment arm, one patient had a complete response
and four patients had partial responses. In the 10 mg daily treatment arm, one
patient had a partial response, six patients had stable disease and one
patient had progressive disease. Among the nine patients evaluated in the 30
mg weekly treatment arm, three patients had partial responses, five patients
had stable disease and one patient had progressive disease. The critical dose-
limiting toxicities occurring in the first cycle of treatment included febrile
neutropenia, oral mucositis and confusion occurring in the 5 mg daily, 10 mg
daily and 30 mg weekly treatment groups, respectively. The most commonly
reported grade 3/4 adverse events (greater than or equal to 10%) suspected of
being related to study treatment were neutropenia, lymphopenia, stomatitis,
leukopenia, alopecia and anemia.
Study details: abstract #406
An open-label, multicenter Phase I trial evaluated daily RAD001 (2.5 mg, 5
mg and 10 mg) and weekly RAD001 (20 mg, 30 mg, 50 mg and 70 mg) in combination
with Navelbine (25 mg/m2 IV over 10-15 min on days 1 and 8 every 21 days) and
Herceptin (2 mg/kg IV over 30 min). All patients entering the study had
progression on, or shortly after, treatment with Herceptin and all had
received prior taxane. The median number of prior chemotherapy regimens was 3
(range: 1-5).
Across treatment arms, there was an overall disease control rate of 62%.
Thirty-four heavily pretreated patients were evaluated to date (fifteen
patients assigned to 5 mg daily, six to 20 mg weekly, and thirteen to 30 mg
weekly). Among the fifteen patients in the 5 mg daily treatment arm, one
patient had a complete response, two patients had partial responses, nine
patients had stable disease and three patients had progressive disease. Among
the six patients in the 20 mg weekly treatment arm, one patient had a partial
response, three patients had stable disease and two patients had progressive
disease. Among the thirteen patients evaluated in the 30 mg weekly treatment
arm, two patients had partial responses, nine patients had stable disease and
two patients had progressive disease. The critical dose-limiting toxicities
(i.e., dose-limiting toxicities in cycle 1) occurring in the 5 mg daily
treatment group included grade 3/4 neutropenia, grade 3 stomatitis, grade 3
fatigue and grade 3 anorexia. In the 30 mg weekly treatment group, grade 3/4
neutropenia was the only critical dose-limiting toxicity. There were no
critical dose-limiting toxicities in the 20 mg weekly RAD001 treatment arm.
The most commonly reported grade 3/4 adverse events (greater than or equal to
10%) suspected of being related to study treatment were neutropenia,
stomatitis and leukopenia.
About breast cancer
In the US, invasive breast cancer affects one in eight women. It is the
second most common cancer among women in the US and the second leading cause
of cancer-related death in women. Breast cancer is expected to claim the lives
of approximately 40,500 women in 2008.
Inside a breast there are many lobes, ducts and vessels that support
several important functions in the body, including reproductive needs and
fighting infection. In breast cancer, some of the cells in the breast begin
growing abnormally and divide more rapidly than healthy cells. The quick
division of cells may cause spreading through the breast, to the lymph nodes
or to other parts of the body.
About RAD001
RAD001, an oral once-daily inhibitor of mTOR, is an investigational drug
being studied in multiple tumor types. In cancer cells, RAD001 provides
continuous inhibition of mTOR, a protein that acts as a central regulator of
tumor cell division, cell metabolism and blood vessel growth.
The safety and efficacy profile of RAD001 has not yet been established in
oncology and there is no guarantee that RAD001 will become commercially
available for oncology indications. The active ingredient in RAD001 is
everolimus. The active ingredient everolimus, is available in different
dosage strengths under the trade name Certican(R) for the prevention of organ
rejection in heart and kidney transplant recipients. Certican was first
approved in the EU in 2003. Certican is not approved in the US.
In addition to breast cancer, RAD001 is being evaluated as a single agent
or in combination with existing therapies in renal cell carcinoma,
neuroendocrine tumors, lymphoma, gastric, lung and other cancers, as well as
tuberous sclerosis complex.
Disclaimer
The foregoing release contains forward-looking statements that can be
identified by terminology such as “potential,” “to start,” “to explore,”
“may,” “to fully explore,” “promising,” “encouraged,” “committed,” “will,” “to
further evaluate,” or similar expressions, or by express or implied
discussions regarding potential regulatory filings or marketing approvals for
RAD001 or regarding potential future revenues from RAD001. 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 RAD001 to be materially different from any future results,
performance or achievements expressed or implied by such statements. There can
be no guarantee that RAD001 will be approved for sale for any oncology
indication in any market. Nor can there be any guarantee that RAD001 will
achieve any particular levels of revenue in the future. In particular,
management’s expectations regarding RAD001 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 Pharmaceuticals Corporation
Novartis Pharmaceuticals Corporation researches, develops, manufactures
and markets leading innovative prescription drugs used to treat a number of
diseases and conditions, including those in the cardiovascular, metabolic,
cancer, organ transplantation, central nervous system, dermatological, GI and
respiratory areas. The company’s mission is to improve people’s lives by
pioneering novel healthcare solutions.
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is an affiliate of Novartis AG which 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 2007, the Group’s continuing
operations (excluding divestments in 2007) achieved net sales of
billion
invested in R&D activities throughout the Group. Headquartered in
Switzerland
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information, please visit http://www.novartis.com.
Novartis Media Relations
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Geoffrey Cook Jill Pozarek
Novartis Oncology Novartis Corporation
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Dana Kahn Cooper
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* In the US, Herceptin is a registered trademark of Genentech, Inc.
Internationally, Herceptin is a registered trademark of Roche.
** Taxol is a registered trademark of Bristol-Myers Squibb Company.
*** Navelbine is a registered trademark of Pierre Fabre Pharmaceuticals
Inc.
SOURCE Novartis Pharmaceuticals Corporation