SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Jan. 28, 2016--
Exelixis, Inc. (NASDAQ:EXEL) today announced that the U.S. Food & Drug
Administration (FDA) has determined the company’s New Drug Application
(NDA) for cabozantinib as a treatment for patients with advanced renal
cell carcinoma (RCC) who have received one prior therapy to be
sufficiently complete to permit a substantive review. The NDA will be
considered officially filed 60 days from the date of the completion of
the submission, or February 20, 2016. The FDA granted Priority Review to
the filing and assigned a Prescription Drug User Fee Act action date of
June 22, 2016.
“With FDA granting Priority Review to our application, Exelixis is one
step closer to offering physicians cabozantinib as an important new
therapeutic option for their patients with advanced renal cell
carcinoma,” said Michael M. Morrissey, Ph.D., president and CEO of
Exelixis. “While we work closely with the FDA during the review process,
Exelixis will continue to execute on our commercial plans, including our
commitment to be ready for a potential launch by April 1st of
A Priority Review designation is granted by the FDA for drugs that, if
approved, would be significant improvements in the treatment, prevention
or diagnosis of a disease. Previously, the FDA granted cabozantinib
Breakthrough Therapy designation (August 2015) and Fast Track
designation (April 2015) for the compound’s proposed RCC indication.
The NDA is based on the 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 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.
On January 11, 2016, Exelixis announced the submission of a Marketing
Authorization Application (MAA) for cabozantinib as a treatment for
patients with advanced RCC who have received one prior therapy to the
European Medicines Agency (EMA). The EMA’s Committee for Medicinal
Products for Human Use (CHMP) previously granted accelerated assessment
to cabozantinib for advanced RCC. As a result, the company’s MAA will be
eligible for a 150-day review, versus the standard 210 days (excluding
clock stops when information is requested by 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
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 an immune 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
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
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
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, including,
without limitation, statements related to: the timing for when the NDA
will be considered officially filed; the impact of Priority Review on
Exelixis’ ability to bring an important new therapeutic option for
patients with advanced renal cell carcinoma; Exelixis’ plan to work with
the FDA during the review process; Exelixis’ intent to continue to
execute on its commercial plans and commitment to be ready for a
potential launch by April 1st of this year; and the
eligibility for an expedited review of the MAA. Words such as “will,”
“continue,” “commitment,” “potential,” “would,” 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. 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: risks and uncertainties related to regulatory review and
approval processes and Exelixis' compliance with applicable legal and
regulatory requirements; the clinical, therapeutic and commercial
potential of cabozantinib; Exelixis' ability to conduct clinical trials
of cabozantinib sufficient to achieve a positive completion; Exelixis’
ability to judge the proper size and level of experience of the
commercialization teams required to support the launch of cabozantinib
for advanced RCC; Exelixis’ ability to protect the company’s
intellectual property rights; 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, the Exelixis logo and COMETRIQ 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.
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.,
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Source: Exelixis, Inc.
Investor Relations and
For Exelixis, Inc.