SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Exelixis, Inc. About Adalat Cc (Nifedipine) with no prescription (NASDAQ:EXEL) today announced positive results from
METEOR, the phase 3 pivotal trial comparing cabozantinib to everolimus
in 658 patients with renal cell carcinoma (RCC) who have experienced
disease progression following treatment with a VEGF receptor tyrosine
kinase inhibitor (TKI). About Ziagen (Abacavir) without Rx In July 2015, Exelixis disclosed that the trial
met its primary endpoint, demonstrating a statistically significant
increase in progression-free survival for patients in the cabozantinib
arm. Women Pack-20 () with no Rx Principal investigator Toni K. Buy Fluox without Rx Choueiri, M.D. Buy Jelly Pack-15 () without prescription will present detailed
data from the late-breaking METEOR abstract (#4-LBA) on Saturday,
September 26, during the Presidential Session I at the European Cancer
Congress (ECC) 2015, which is being held September 25-29 in Vienna. Buy Colon online The
METEOR data and an accompanying editorial were also published today in The
New England Journal of Medicine.
As announced in July, the METEOR trial met its primary endpoint of
demonstrating a statistically significant increase in progression-free
survival (PFS) for cabozantinib as compared to everolimus, as determined
by an independent radiology committee. http://webmd-help.blogspot.com Per the trial protocol, the
primary analysis was conducted among the first 375 patients randomized
to ensure sufficient follow up and a PFS profile that would not be
primarily weighted toward early events. The median PFS was 7.4 months
for the cabozantinib arm versus 3.8 months for the everolimus arm,
corresponding to a 42% reduction in the rate of disease progression or
death for cabozantinib as compared to the everolimus arm (hazard ratio
[HR]=0.58, 95% confidence interval [CI] 0.45-0.75, p<0.001).
Cabozantinib effects were favorable across patient stratification
subgroups including the number of prior VEGF receptor TKI therapies and
commonly applied RCC risk criteria developed by Motzer et al.
In a post-hoc subset analysis of patients who had received sunitinib,
the most commonly used first-line therapy, as their only prior VEGF
receptor TKI, the median PFS for cabozantinib-treated patients (n=76)
was 9.1 months versus 3.7 months for everolimus-treated patients (n=77).
This corresponds to a 59% reduction in the rate of disease progression
or death for patients treated with cabozantinib (HR=0.41, 95% CI
0.28-0.61).
“In the METEOR trial, cabozantinib significantly improved
progression-free survival as compared to everolimus, a commonly-used
standard of care, in both the full study population for the primary
endpoint analysis as well as in the subgroup of patients previously
treated with sunitinib only. Cabozantinib was also associated with a
safety profile similar to other VEGF receptor TKIs used to treat renal
cell carcinoma,” said Toni K. Choueiri, M.D., clinical director of the
Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute,
and METEOR’s principal investigator. “Uniquely, treatment with
cabozantinib resulted in a strong trend towards improving overall
survival, which is unprecedented as compared with other studies to date
evaluating TKIs. The totality of the data support cabozantinib as a
potential new treatment option for RCC patients whose disease has
progressed following VEGF receptor-targeting therapy.”
Data pertaining to overall survival (OS) in the entire study population
of 658 patients, a secondary endpoint of the trial, were immature at the
data cutoff. As previously announced, a pre-specified interim analysis
triggered by the primary analysis for PFS showed a strong trend in OS
favoring cabozantinib (HR=0.67, 95% CI 0.51-0.89, p=0.005) At the time
of the interim analysis, the p-value of 0.0019 to achieve statistical
significance was not reached, and the trial will continue to the final
analysis of OS anticipated in 2016. Objective response rate, another
secondary endpoint, was significantly higher with cabozantinib (21%) as
compared with everolimus (5%; p < 0.001). Treatment discontinuations for
adverse events unrelated to progressive disease were 9% and 10% for
cabozantinib and everolimus, respectively.
“These results from the METEOR trial suggest that cabozantinib has the
potential to become a new and differentiated treatment option for
patients with renal cell carcinoma who have progressed following VEGF
receptor tyrosine kinase therapy, the most commonly-utilized treatment
in the first-line setting,” said Michael M. Morrissey, Ph.D., Exelixis’
president and chief executive officer. “Exelixis is working quickly to
share the data with regulators in the United States and European Union.
We are on track to complete our U.S. NDA filing by the end of this year,
where cabozantinib has received Breakthrough Therapy Designation, and
expect a European filing to follow in early 2016. We look forward to
advancing these regulatory processes in hopes of bringing cabozantinib
to the renal cell carcinoma community as soon as possible.”
653 patients were evaluable for safety. Median duration of exposure was
7.6 months for cabozantinib and 4.4 months for everolimus. Investigators
employed dose reductions to manage adverse events (AE), and 60% of
patients on the cabozantinib arm and 25% of patients on the everolimus
arm had dose reductions. The median average daily dose was 44 mg for
cabozantinib and 9 mg for everolimus. The incidence of adverse events
(any grade), regardless of causality, was 100% with cabozantinib and
more than 99% with everolimus. Serious adverse events occurred in 40% of
cabozantinib patients and 43% of everolimus patients. The most common
AEs regardless of causality, grade 3 or higher, for cabozantinib were:
hypertension (15%), diarrhea (11%), fatigue (9%), and hand-foot syndrome
(8%). The most common AEs regardless of causality, grade 3 or higher,
for everolimus were: anemia (16%), fatigue (7%), hyperglycemia (5%), and
dyspnea (4%). Grade 5 adverse events occurred in 6.6% of patients in the
cabozantinib arm and in 7.8% of patients in the everolimus arm, and were
primarily related to disease progression. Treatment-related grade 5
events occurred in one patient (0.3%; death not otherwise specified) in
the cabozantinib arm and 2 patients (0.6%; aspergillus infection and
aspiration pneumonia) in the everolimus arm.
Cabozantinib is currently marketed in capsule form under the brand name
COMETRIQ® in the United States for the treatment of
progressive, metastatic medullary thyroid cancer (MTC), and in the
European Union for the treatment of adult patients with progressive,
unresectable locally advanced or metastatic MTC. COMETRIQ is not
indicated for patients with advanced RCC or any other form of the
disease. In the METEOR trial, and all other cancer trials currently
underway, Exelixis is investigating a tablet formulation of cabozantinib
distinct from the COMETRIQ capsule form.
Webcast for the Investment Community
Exelixis will host a live webcast on Saturday, September 26, 2015,
following the METEOR presentation at ECC 2015. The webcast will begin at
12:30 p.m. EDT / 9:30 a.m. PDT (18:30 local Vienna time). During the
webcast, Exelixis management and Dr. Toni Choueiri, principal
investigator of the METEOR trial, will review and provide context for
the data presented at the Congress.
To access the webcast link, log onto .exelixis.com
and proceed to the Event Calendar page under Investors & Media. Please
connect to the company’s website at least 15 minutes prior to the
webcast to ensure adequate time for any software download that may be
required to listen to the webcast. Alternatively, you may access the
webcast at this address: edge.media-server.com/m/p/c7qgq2ma/lan/en.
An archived replay of the webcast will be available on the Event
Calendar page under Investors & Media at .exelixis.com
for one year. An audio-only phone replay will be available until 11:59
p.m. EDT on September 28, 2015. Access numbers for the phone replay are:
(855) 859-2056 (domestic) and (404) 537-3406 (international); the
passcode is 47549145.
About Advanced Renal Cell Carcinoma
The American Cancer Society’s 2015 statistics cite kidney cancer as
among the top ten most commonly diagnosed forms of cancer among both men
and women in the United States.1 Clear cell renal cell
carcinoma is the most common type of kidney cancer in adults.2
If detected in its early stages, the five-year survival rate for RCC is
high; however, the five-year survival rate for patients with advanced or
late-stage metastatic RCC is under 10 percent, with no identified cure
for the disease.3
Treatments for advanced RCC had historically been limited to cytokine
therapy (e.g., interleukin-2 and interferon) until the introduction of
targeted therapies into the RCC setting a decade ago. In the second and
later-line setting, which encompasses approximately 17,000 drug-eligible
patients in the U.S. and 37,000 globally,4 two therapies have
been approved for the treatment of patients who have received prior VEGF
receptor TKIs. However, despite the availability of several therapeutic
options, currently approved agents have shown little differentiation in
terms of efficacy and have demonstrated only modest PFS benefit in
patients refractory to sunitinib, a commonly-used first-line therapy.
The majority of clear cell RCC tumors exhibit down-regulation of von
Hippel-Lindau (VHL) protein function, resulting in a stabilization of
the hypoxia-inducible transcription factors (HIFs) and consequent
up-regulation of VEGF, MET, and AXL.5 The up-regulation of
VEGF may contribute to the angiogenic nature of clear cell RCC, and
expression of MET or AXL may be associated with tumor cell viability, a
more invasive tumor phenotype, and reduced overall survival. 6
Up-regulation of MET in clear cell RCC has also been shown to occur in
response to treatment with VEGF receptor TKIs in preclinical models,
indicating a potential role for MET in the development of resistance to
these therapies.7
About Cabozantinib
Cabozantinib inhibits the activity of tyrosine kinases including MET,
VEGF receptors, AXL, and RET. These receptor tyrosine kinases are
involved in both normal cellular function and in pathologic processes
such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of
the tumor microenvironment.
COMETRIQ® (cabozantinib capsules) is currently approved by
the U.S. Food and Drug Administration for the treatment of progressive,
metastatic medullary thyroid cancer (MTC).
The European Commission granted COMETRIQ conditional approval for the
treatment of adult patients with progressive, unresectable locally
advanced or metastatic MTC. Similar to another drug approved in this
setting, the approved indication states that for patients in whom
Rearranged during Transfection (RET) mutation status is not known or is
negative, a possible lower benefit should be taken into account before
individual treatment decisions.
Important Safety Information, including Boxed WARNINGS
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
Serious and sometimes fatal gastrointestinal perforations and
fistulas occur in COMETRIQ-treated patients.
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated
patients.
COMETRIQ treatment results in an increase in thrombotic events, such
as heart attacks.
Wound complications have been reported with COMETRIQ.
COMETRIQ treatment results in an increase in hypertension.
Osteonecrosis of the jaw has been observed in COMETRIQ-treated
patients.
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients
treated with COMETRIQ.
The kidneys can be adversely affected by COMETRIQ. Proteinuria and
nephrotic syndrome have been reported in patients receiving COMETRIQ.
Reversible Posterior Leukoencephalopathy Syndrome has been observed
with COMETRIQ.
Avoid administration of COMETRIQ with agents that are strong CYP3A4
inducers or inhibitors.
COMETRIQ is not recommended for use in patients with moderate or
severe hepatic impairment.
COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions
(>=25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia
syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue,
oral pain, hair color changes, dysgeusia, hypertension, abdominal pain,
and constipation. The most common laboratory abnormalities (>=25%) are
increased AST, increased ALT, lymphopenia, increased alkaline
phosphatase, hypocalcemia, neutropenia, thrombocytopenia,
hypophosphatemia, and hyperbilirubinemia.
Please see full U.S. prescribing information, including Boxed WARNINGS,
at .COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf
Please refer to the full European Summary of Product Characteristics for
full European Union prescribing information, including contraindication,
special warnings and precautions for use at .sobi.com
once posted.
About Exelixis
Exelixis, Inc. is a biopharmaceutical company committed to developing
small molecule therapies for the treatment of cancer. Exelixis is
focusing its development and commercialization efforts primarily on
cabozantinib, its wholly-owned inhibitor of multiple receptor tyrosine
kinases. Another Exelixis-discovered compound, cobimetinib, a selective
inhibitor of MEK, received its first regulatory approval in Switzerland
and is being evaluated by Roche and Genentech (a member of the Roche
Group) in a broad development program under a collaboration with
Exelixis. For more information, please visit the company s web site at .exelixis.com.
Forward-Looking Statements
This press release contains forward-looking statements that are subject
to risk and uncertainty, including, without limitation, cabozantinib’s
potential as a new and differentiated treatment option for RCC patients
whose disease has progressed following VEGF receptor-targeting therapy;
that the METEOR trial will continue to the final analysis of OS in 2016;
and that Exelixis will complete our U.S. NDA filing by the end of 2015
and our EU filing in early 2016. Words such as “will,” “potential”,
“suggest”, “expect”, “look forward,” “hope”, and “as soon as possible”
or other similar expressions identify forward-looking statements, but
the absence of these words does not necessarily mean that a statement is
not forward-looking. In addition, any statements that refer to
expectations, projections or other characterizations of future events or
circumstances are forward-looking statements. These forward-looking
statements are based upon Exelixis’ current plans, assumptions, beliefs,
expectations, and projections. Actual results and the timing of events
could differ materially from those anticipated in the forward-looking
statements, which include, without limitation: risks related to the
clinical, therapeutic and commercial potential of cabozantinib; risks
related to Exelixis ability to conduct clinical trials of cabozantinib
sufficient to achieve a positive completion; risks and uncertainties
related to regulatory review and approval processes and Exelixis
compliance with applicable legal and regulatory requirements; risks
related to market competition, changes in economic and business
conditions, and other factors discussed under the caption “Risk Factors”
in Exelixis’ quarterly report on Form 10-Q filed with the Securities and
Exchange Commission (SEC) on August 11, 2015, and in Exelixis’ other
filings with the SEC. The forward-looking statements made in this press
release speak only as of the date of this press release. Exelixis
expressly disclaims any duty, obligation or undertaking to release
publicly any updates or revisions to any forward-looking statements
contained herein to reflect any change in Exelixis’ expectations with
regard thereto or any change in events, conditions or circumstances on
which any such statements are based.
Exelixis, the Exelixis logo, and COMETRIQ are registered U.S.
trademarks.
1 Cancer Facts & Figures 2015. American Cancer Society.
Available at .cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf
2 Jonasch et al., BMJ (2014) vol. 349, g4797.
3 .cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-survival-rates
4 ACS Cancer Facts and Figures 2015; Heng et al., Ann
Oncol (2012) vol. 23 no. 6; internal data on file; Motzer et al., N Engl
J Med (2007) vol. 356 no. 2; NCIN (UK) report, April 2014, Available at .ncin.org.uk/view?rid=2676.
5 Harschman and Choueiri, Cancer J. 2013 v19 316-323;
Rankin et al., PNAS, 2014.
6 Bommy-Reddi et al., PNAS, 2008; Gibney et al., Ann.
Oncol. 2013 v24 343-349; Koochekpour et al., Mol. Cell. Biol. 1999, v19
5902-5912; Rankin et al., PNAS, 2014.
7 Ciamporcero et al., MolCancerTher, 2014.
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