SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Dec. 23, 2015--
Exelixis, Inc. (NASDAQ:EXEL) today announced that it has completed the
submission of its rolling New Drug Application (NDA) with the U.S. Food
and Drug Administration (FDA) for cabozantinib as a treatment for
patients with advanced renal cell carcinoma (RCC) who have received one
prior therapy. Exelixis has requested Priority Review as part of the NDA
filing.
In August 2015, the FDA granted Breakthrough Therapy designation to
cabozantinib for this potential advanced RCC indication. Breakthrough
Therapy designation can expedite 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 the involvement of FDA senior
leadership in the review process, rolling submission, and other
benefits. Prior to receiving Breakthrough Therapy designation,
cabozantinib received Fast Track designation for its potential advanced
RCC indication in April 2015.
“Completing the submission of our rolling New Drug Application brings us
closer to our goal of improving the treatment options for patients with
advanced kidney cancer,” said Michael M. Morrissey, Ph.D., president and
chief executive officer of Exelixis. “Following the release of positive
top-line results from our phase 3 pivotal trial in July, the Exelixis
team worked expeditiously to complete the U.S. regulatory filing by year
end. We look forward to continuing to work with the FDA team during the
review process.”
The NDA submission is based on results of METEOR, a phase 3 pivotal
trial comparing cabozantinib to everolimus in patients with advanced RCC
who experienced disease progression following treatment with a VEGF
receptor tyrosine kinase inhibitor. In July 2015, Exelixis announced
top-line results from METEOR demonstrating that the trial had met its
primary endpoint of improving progression-free survival; compared with
everolimus, cabozantinib was associated with a 42% reduction in the rate
of disease progression or death. These data were later presented at the
European Cancer Congress in September 2015 and concurrently published in The
New England Journal of Medicine.
In the European Union, Exelixis aims to complete its Marketing
Authorization Application (MAA) in early 2016. The European Medicines
Agency’s Committee for Medicinal Products for Human Use (CHMP) recently
granted accelerated assessment to cabozantinib for advanced RCC. As a
result, when filed, the company’s MAA may be eligible for a 150-day
review, versus the standard 210 days (excluding clock stops when
information is requested from CHMP).
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 RCC. 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. The
tablet formulation of cabozantinib is the subject of the NDA for
advanced RCC.
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 U.S.1 Clear cell RCC 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
Until the introduction of targeted therapies into the RCC setting a
decade ago, treatments for metastatic RCC had historically been limited
to cytokine therapy (e.g., interleukin-2 and interferon). In the second
and later-line settings, which encompass approximately 17,000
drug-eligible patients in the U.S. and 37,000 globally,4 two
small-molecule therapies and a checkpoint inhibitor have been approved
for the treatment of patients who have received prior VEGF receptor
TKIs. The currently approved small-molecule agents have shown little
differentiation in terms of efficacy and have demonstrated only modest
progression-free survival 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, either due to gene inactivation or
epigenetic silencing, 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 and AXL 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 and AXL 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.
Cabozantinib, marketed under the brand name COMETRIQ®, 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, COTELLIC™ (cobimetinib),
a selective inhibitor of MEK, has been approved in Switzerland, the
United States, and the European Union, 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 website at www.exelixis.com.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements that are subject
to risk and uncertainty, including, without limitation, the impact of
the FDA’s Breakthrough Therapy designation on the development and review
of cabozantinib as a treatment for patients with advanced RCC who have
received one prior therapy; Exelixis’ goal of improving the treatment
options for patients with advanced kidney cancer; Exelixis’ plan to
continue to work with the FDA team during the review process; and
Exelixis’ plan to complete its MAA in the European Union in early 2016
and the potential for an expedited review. Words such as “can,”
“intended”, “may,” “goal,” “look forward,” and “aims” 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 November 10, 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 and the Exelixis logo are registered U.S. trademarks, and
COTELLIC is a U.S. trademark.
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; Rankin et al., PNAS, 2014.
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Source: Exelixis, Inc.
Investors Contact:
Exelixis, Inc.
Susan
Hubbard, 650-837-8194
Investor Relations and Corporate
Communications
shubbard@exelixis.com
or
Media
Contact:
For Exelixis, Inc.
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415-994-0040
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