New data show RAD001
(everolimus) may provide an important new treatment option for patients
with advanced kidney cancer who have failed standard therapies.
The interim study findings demonstrated that RAD001 significantly
extended the time without tumor growth from 1.9 to 4 months and reduced the
risk of cancer progression by 70% (hazard ratio = 0.30 with 95% CI 0.22 to
0.40; p- value < 0.0001). The study, RECORD-1 (REnal Cell cancer treatment
with Oral RAD001 given Daily), will be presented at the 44th annual meeting
of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois,
US on Saturday, May 31, 2008.
Earlier this year, an independent data monitoring committee stopped the
RECORD-1 trial after interim results showed that patients receiving RAD001
experienced a significantly longer time without their cancer worsening
compared to patients receiving placebo. The trial included patients whose
cancer had stopped responding to approved treatments for renal cell
carcinoma (RCC), such as Nexavar(R) (sorafenib) or Sutent(R) (sunitinib),
or both.
RAD001 is a once-daily oral therapy that may offer a new approach to
cancer treatment by continuously inhibiting the mTOR protein, a central
regulator of tumor cell division and blood vessel growth in cancer cells.
"This is the first study to show clinical benefit in patients with
advanced kidney cancer who have experienced treatment failure with the most
commonly used first-line therapies," said Robert J. Motzer, MD, attending
physician, Memorial Sloan-Kettering Cancer Center, New York, and principal
investigator of the RECORD-1 trial. "The results show RAD001 extended
progression-free survival in patients regardless of their prior treatments,
risk status, age, or gender."
During the second half of 2008, the interim results from RECORD-1 will
be used to submit a new drug application for RAD001 as a treatment for
metastatic renal cell carcinoma.
"As we will see in presentations at the upcoming meeting, RAD001 has
the potential to benefit patients living with a variety of cancers
including neuroendocrine, breast, gastric, and lung," said David Epstein,
CEO and President of Novartis Oncology. "We look forward to updates from
trials in pancreatic neuroendocrine tumors before year-end."
RECORD-1 results
RECORD-1 is the largest Phase III clinical trial investigating the
effects of an oral mTOR inhibitor in metastatic RCC. It is a randomized,
double-blind placebo-controlled multicenter trial of more than 400 patients
with RCC whose cancer worsened despite prior treatment, including Nexavar
or Sutent, or both. In addition, prior therapy with Avastin, interferon,
and interleukin-2 was allowed.
The primary endpoint of RECORD-1 was progression-free survival (PFS)
assessed via a blinded, independent central review and defined as the
amount of time between randomization and first documented disease
progression or death due to any cause. Results of the study demonstrated a
statistically significant improvement in PFS for RAD001 compared to placebo
(hazard ratio = 0.30 with 95% CI 0.22 to 0.40; p-value < 0.0001; median PFS
4 months vs. 1.9 months, respectively).
Secondary endpoints included comparison of overall survival, objective
response rate, quality of life, safety, and pharmacokinetics. There was no
significant difference in overall survival between the RAD001 and placebo
groups (hazard ratio = 0.83 with 95% CI 0.50 to 1.37; p-value = 0.23). The
study design allowed patients to be unblinded at the time of radiological
disease progression; patients receiving placebo were allowed to cross over
to receive RAD001. There was no significant difference in objective
response rate between the RAD001 and placebo groups (1% vs. 0% of
responders). However, in a central review among patients evaluable for best
percentage change in target lesions (223 and 107 in RAD001 and placebo
arms, respectively), tumor shrinkage was observed in 50% of patients
receiving RAD001 during the double- blind portion of the study versus 8% of
patients receiving placebo. Quality of life measurements taken throughout
the study showed no significant difference between the RAD001 and placebo
groups.
Safety findings in the study were consistent with those seen in prior
Phase II studies. The most frequent adverse events in patients who took
RAD001 included mouth sores (40%), feelings of weakness (37%), and rash
(25%). There was a low incidence of grade 3 or 4 drug-related adverse
events (greater than or equal to 1% of patients listed): mouth sores (3%),
lung inflammation (3%), infection (3%), tiredness/feelings of weakness
(4%), diarrhea (1%), mucosal inflammation (1%), and difficulty breathing
(1%). The trial had a low rate of adverse drug reactions leading to
discontinuation among patients who took RAD001 (6%).
About renal cell carcinoma (RCC)
In the United States, kidney cancer accounts for approximately 3% of
all adult cancers. RCC, the most common type of kidney cancer, accounts for
approximately 90% of malignant kidney tumors. In RCC, cancer cells develop
in the lining of the kidney's tubes and grow into a tumor.
About RAD001
RAD001, an oral inhibitor of mTOR, is an investigational drug being
studied in multiple tumor types. In cancer cells, RAD001 inhibits mTOR, a
protein that acts as a central regulator of tumor cell division, cell
metabolism, and blood vessel growth. RAD001 is a once-daily oral therapy
that provides continuous inhibition of mTOR.
In addition to RCC, RAD001 is presently being evaluated in
neuroendocrine tumors, lymphoma, other cancers, and tuberous sclerosis as a
single agent or in combination with existing cancer therapies.
As an investigational compound, the safety and efficacy profile of
RAD001 has not yet been established in oncology. Access to RAD001 is
available only through carefully controlled and monitored clinical trials.
These trials are designed to better understand the potential benefits and
risks of the compound. Because of the uncertainty of clinical trials, there
is no guarantee that RAD001 will ever be commercially available for
oncology indications anywhere in the world. Everolimus is approved 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 and is available in more than 60 countries.
Disclaimer
The foregoing release contains forward-looking statements that can be
identified by terminology such as "risk," "potential," "may," "proposed,"
"will," "potential," "look forward," or similar expressions, or by express
or implied discussions regarding potential future regulatory filings or
approvals for RAD001 or regarding potential future revenues from RAD001.
Such forward- looking statements reflect the current views of the Company
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 submitted for approval, or approved for sale in any market
for any oncology indication. 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, 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 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.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals
Corporation is an affiliate of Novartis AG (NYSE: NVS), which provides
healthcare solutions that address the evolving needs of patients and
societies. Focused solely on growth areas in healthcare, Novartis offers a
diversified portfolio to best meet these needs: innovative medicines,
cost-saving generic pharmaceuticals, preventive vaccines and 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 USD 38.1
billion and net income of USD 6.5 billion. Approximately USD 6.4 billion
was invested in R&D activities throughout the Group. Headquartered in
Basel, Switzerland, Novartis Group companies employ approximately 98,000
full-time associates and operate in over 140 countries around the world.
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