-- Provides Opportunity to Expedite Regulatory Timelines --
-- Exelixis Plans to Complete Submission of Cabozantinib U.S. NDA
for Advanced RCC in 2015 --
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Aug. 24, 2015--
Exelixis, Inc. (NASDAQ:EXEL) today announced the U.S. Food & Drug
Administration (FDA) has granted Breakthrough Therapy Designation to
cabozantinib, Exelixis’ lead compound, as a potential treatment for
patients with advanced renal cell carcinoma (RCC) who have received one
prior therapy. Created in 2012, FDA’s Breakthrough Therapy Designation
expedites the development and review of drugs that are intended to treat
serious or life-threatening diseases, and for which preliminary clinical
evidence indicates the drug may demonstrate substantial improvement over
existing therapies on one or more clinically significant endpoints.
Drugs that receive Breakthrough Therapy Designation may benefit from
involvement of FDA senior managers in the review process, potential
rolling submission and/or Priority Review of a sponsor’s New Drug
Application (NDA), and other benefits.
“Receiving Breakthrough Therapy Designation is an important regulatory
achievement for cabozantinib in renal cell carcinoma,” said Michael M.
Morrissey, Ph.D., president and chief executive officer of Exelixis.
“Following the positive top-line results announced in July and a
productive dialogue with the FDA, Exelixis believes we can expedite our
regulatory timelines and complete the cabozantinib NDA submission in
advanced RCC prior to the end of 2015. We look forward to working
closely with the FDA during the submission and review process, keeping
in mind our ultimate goal of bringing a new therapeutic option to the
renal cell carcinoma community as soon as possible.”
Cabozantinib received Breakthrough Therapy Designation based on the
results of METEOR, the phase 3 pivotal trial comparing cabozantinib to
everolimus in patients with RCC who experienced disease progression
following treatment with a VEGF receptor tyrosine kinase inhibitor
(TKI). In top-line results announced in July 2015, METEOR met its
primary endpoint, demonstrating a statistically significant increase in
progression-free survival (PFS) for cabozantinib as compared to
everolimus in the first 375 patients randomized as determined by an
independent radiology review committee. Cabozantinib reduced the rate of
disease progression or death by 42 percent compared to everolimus
(hazard ratio [HR]=0.58, 95 percent confidence interval [CI] 0.45-0.75,
p<0.0001).
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. A distinct tablet
formulation of cabozantinib is under investigation for advanced renal
cell carcinoma and other types of cancer. COMETRIQ is not indicated for
patients with advanced RCC or any other form of the disease.
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 www.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 www.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, 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.
Forward-Looking Statements
This press release contains forward-looking statements that are subject
to risk and uncertainty, including, without limitation, that the FDA’s
grant of Breakthrough Therapy Designation may result in expedited
regulatory timelines, Priority Review, and other benefits, which may
permit Exelixis to submit an NDA for RCC prior to the end of 2015; that
the METEOR trial will continue to the final analysis of OS, which is
anticipated in early 2016; and that detailed results of the trial will
be presented at an upcoming medical conference. 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 value 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.
1Cancer Facts & Figures 2015. American Cancer Society.
Available at http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf
2Jonasch et al., BMJ (2014) vol. 349, g4797.
3http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-survival-rates
4ACS 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 http://www.ncin.org.uk/view?rid=2676.
5Harschman and Choueiri, Cancer J. 2013 v19 316-323;
Rankin et al., PNAS, 2014.
6Bommy-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.
7Ciamporcero et al., MolCancerTher, 2014.
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Source: Exelixis, Inc.
Investors Contact:
Exelixis, Inc.
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Investor Relations and
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