|[September 01, 2014]
Exelixis Announces Results from the COMET-1 Phase 3 Pivotal Trial of Cabozantinib in Men with Metastatic Castration-Resistant Prostate Cancer
SOUTH SAN FRANCISCO, Calif. --(Business Wire)--
Exelixis, Inc. (NASDAQ:EXEL) today announced top-line results from the
final analysis of COMET-1, the phase 3 pivotal trial of cabozantinib in
men with metastatic castration-resistant prostate cancer (mCRPC) whose
disease progressed after treatment with docetaxel as well as abiraterone
and/or enzalutamide. The trial did not meet its primary endpoint of
demonstrating a statistically significant increase in overall survival
(OS) for patients treated with cabozantinib as compared to prednisone.
The median OS for the cabozantinib arm of the trial was 11.0 months
versus 9.8 months for the prednisone arm (hazard ratio 0.90; 95%
confidence interval 0.76 - 1.06; p value 0.212).
The COMET-1 results are the subject of ongoing analyses. Exelixis will
submit additional data, including secondary and exploratory endpoints,
for presentation at a future medical conference. Besides OS, the
exploratory endpoint of progression-free survival (PFS) as assessed by
the investigators is the only time-to-event-based endpoint for which
data are available. Median PFS was 5.5 months for the cabozantinib arm
of the trial versus 2.8 months for the prednisone arm (hazard ratio
0.50; 95% confidence interval 0.42 - 0.60; p value <0.0001). Safety data
were consistent with those observed in earlier-stage trials of
cabozantinib in mCRPC.
As a result of the outcome of COMET-1, Exelixis will initiate a
significant workforce reduction to enable the company to focus its
financial resources on the late-stage clinical trials of cabozantinib in
metastatic renal cell carcinoma (the METEOR trial) and advanced
hepatocellular carcinoma (the CELESTIAL trial). The company will reduce
its workforce by approximately 70 percent, or approximately 160
employees, resulting in approximately 70 remaining employees.
Exelixis anticipates the one-time restructuring charge associated with
the workforce reduction to be approximately $6 million - $8 million,
with the majority to be completed by the end of the fourth quarter of
2014. As a result of this and other cost-saving measures contemplated,
the company anticipates that it has sufficient cash to support its
operations through the release of top-line results of the METEOR trial
next year. More financial details will be provided by the company in its
third quarter 2014 financial report.
"We are very disappointed that COMET-1 did not meet its primary endpoint
of extending overall survival in men with mCRPC," said Michael M.
Morrissey, Ph.D., president and chief executive officer of Exelixis. "We
are grateful to the patients, physicians, nurses, caregivers, and other
study team members who participated in the trial. We remain focused on
the development program for cabozantinib beyond mCRPC, including the
ongoing METEOR and CELESTIAL phase 3 pivotal trials, from which we
expect top-line data in 2015 and 2017, respectively."
Dr. Morrissey continued, "We have thoughtfully prepared for this
scenario and the resulting very difficult decisions. The workforce
reduction we have announced today is necessary to significantly reduce
our corporate operating expenses. I would like to personally express my
deep appreciation to the talented and dedicated Exelixis employees who
will be impacted by these actions, both for their commitment to Exelixis
and for their tremendous contributions to patients with cancer."
Based on the outcome of COMET-1, Exelixis has deprioritized the clinical
development of cabozantinib in mCRPC. Enrollment in COMET-2, which is
the second pivotal trial in mCRPC and evaluates pain palliation, has
been halted. The company expects top-line data before the end of this
year. Based on the outcome of COMET-2, Exelixis will discuss with
regulatory authorities the potential regulatory path, if any, of
cabozantinib in mCRPC. Other company-sponsored studies in mCRPC,
including a randomized phase 2 study of cabozantinib in combination with
abiraterone, will also be halted.
Investor Conference Call and Webcast
Exelixis management will discuss the COMET-1 top-line results and the
resulting corporate initiatives during a conference call beginning at
8:30 a.m. EDT/ 5:30 a.m. PDT tomorrow, Tuesday, September 2, 2014. To
join the call, participants may dial 877-546-5020 (domestic) or
857-244-7552 (international) and use passcode 60161764. To listen to a
live webcast of the conference call, please visit the Event Calendar
page under Investors & Media at www.exelixis.com.
An achived replay of the conference call will be available on the Event
Calendar page under Investors & Media at www.exelixis.com
and via phone until 11:59 p.m. EDT on October 2, 2014. Access numbers
for the phone replay are: 888-286-8010 (domestic) and 617-801-6888
(international); the passcode is 69796111.
About the COMET-1 Phase 3 Pivotal Trial
COMET-1 was a randomized, double-blind, controlled trial that enrolled
960 patients with mCRPC who had previously been treated with and
progressed after treatment with docetaxel, abiraterone and/or
enzalutamide. The primary endpoint of the trial was OS, and the
secondary endpoint was bone scan response as assessed by an independent
radiology committee. All patients in the trial had bone metastases, and
there was no limit to the number or type of prior treatments. Patients
were randomized 2:1 to receive cabozantinib (60 mg daily) or prednisone
(5 mg twice daily). The trial was event-driven and had 90% power to
detect a 25% reduction in the risk of death (HR = 0.75) at the time of
final analysis, which required 578 events.
Cabozantinib inhibits the activity of tyrosine kinases including MET,
VEGFRs 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
COMETRIQ® (cabozantinib) 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
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
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
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,
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 www.sobi.com
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
COMETRIQ® (cabozantinib), its wholly-owned inhibitor of
multiple receptor tyrosine kinases. Another Exelixis-discovered
compound, cobimetinib, a highly selective inhibitor of MEK, 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 www.exelixis.com.
This press release contains forward-looking statements, including,
without limitation, statements related to: the continued development and
clinical, therapeutic and commercial potential of, and opportunities
for, cabozantinib; the results and implications of completed, partial,
and ongoing clinical data analyses; future data presentations; future
discussions with regulatory authorities; anticipated developments and
timing with respect to Exelixis' ongoing phase 3 pivotal trials of
cabozantinib; plans to focus financial resources, to halt
company-sponsored studies in mCRPC; and plans to initiate a workforce
reduction, including the objectives and anticipated timing thereof.
Words such as "will," "enable," "focus," "anticipates," "expect,"
"ensure," "potential," 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, estimates and
projections. Forward-looking statements involve risks and uncertainties.
Exelixis' actual results and the timing of events could differ
materially from those anticipated in the forward-looking statements as a
result of these risks and uncertainties, which include, without
limitation: the availability of data at the expected times; risks
related to the potential failure of cabozantinib to demonstrate safety
and efficacy in clinical study; the clinical, therapeutic and commercial
value of cabozantinib; 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;
the general sufficiency of Exelixis' capital and other resources and the
specific risk of unforeseen expenses that could diminish Exelixis'
financial ability to support its operations through the release of
top-line METEOR results; the uncertain timing and level of expenses
associated with the development of cabozantinib; risks related to
Exelixis' ability to implement the referenced workforce reduction
according to plan and its impact on Exelixis' business; expenses and
charges resulting from the referenced workforce reduction; 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 (News - Alert)) on July 31, 2014 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
Exelixis, the Exelixis logo, and COMETRIQ are registered U.S.
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