-- Company Initiates Phase III “ADVOCATE”
Clinical Trial for Complement Receptor Inhibitor Avacopan in ANCA
Vasculitis; Development Path Outlined in Rare Kidney Disease for
Chemokine Receptor Inhibitor ‘CCX140’ --
ChemoCentryx, Inc., (Nasdaq:CCXI), today provided a corporate
update on its pipeline progress and development strategy for its
expanding rare renal disease portfolio, which includes the
Company’s late stage compounds avacopan (CCX168) as well as CCX140.
Avacopan and CCX140 are potent, orally-administered small molecules
that selectively inhibit the complement C5a receptor (C5aR), and
the chemokine receptor known as CCR2, respectively. Both compounds
are in clinical development for the treatment of serious renal
diseases.
CCX140: Overview of Recent Agreement with Vifor Pharma
and Expanding the Multi-Product Kidney Health Alliance
In December 2016, ChemoCentryx announced the expansion of its
kidney health alliance with Vifor Pharma to include the development
and commercialization of CCX140 for renal diseases.
This second alliance expands upon a May 2016 agreement between
the two companies through which Vifor Pharma licensed rights to
commercialize avacopan (formerly called CCX168) for orphan and rare
renal diseases in Europe and certain other territories. Combined,
the two alliances included $135 million in upfront cash
commitments, $1.2 billion in potential development, regulatory and
sales milestone payments and royalties in the teens to mid-twenties
on net sales in the Vifor Pharma territories.
The December 2016 alliance will focus initially on the
development of CCX140 in rare kidney diseases. Specifically, in
2017 ChemoCentryx plans to initiate controlled trials of CCX140 in
patients with the rare renal disease known as focal segmental
glomerulosclerosis (FSGS). Currently there are no FDA
approved treatments for FSGS, a rare form of chronic disease kidney
which affects approximately 80,000 patients in the U.S. and Europe,
with 5,500-9,500 new cases each year. Progressive FSGS can lead to
end-stage renal disease, ultimately requiring kidney transplant or
renal dialysis and total health expenditures of hundreds of
thousands of dollars each year per patient. CCX140 successfully
completed a Phase II clinical trial in patients with diabetic
nephropathy (DN), a form of chronic kidney disease (CKD). CCX140
treatment in DN resulted in a statistically significant reduction
in proteinuria. Reduction in proteinuria is widely considered as a
beneficial outcome in the treatment of CKD including FSGS, and
experts regard the reduction of proteinuria as the likely
registration endpoint for a new therapeutic in FSGS.
ChemoCentryx is responsible for the clinical development of
CCX140. Development costs in FSGS are equally shared between the
parties, with ChemoCentryx’s expenditures being capped.
ChemoCentryx retains marketing rights for CCX140 for rare renal
disease including FSGS in the U.S. and China, while Vifor Pharma
has commercialization rights in the rest of the world.
Separately, Vifor Pharma will retain an option, exercisable at a
defined future time, to solely fund, develop, and commercialize
(with pre-defined economics to ChemoCentryx under such option)
CCX140 in more prevalent forms of CKD. In the event Vifor
Pharma exercises its CKD option, ChemoCentryx would retain
co-promotion rights in the U.S.
Developing and ultimately marketing CCX140 in FSGS adds a second
drug candidate to ChemoCentryx’s rare renal disease portfolio (in
addition to avacopan), representing a strategic complement to the
Company’s forward integration plan.
Avacopan: Initiation of Worldwide Phase III “ADVOCATE”
Clinical Trial in AAV
In December 2016, the Company initiated the ADVOCATE (Avacopan
Development in Vasculitis to Obtain Corticosteroid elimination and
Therapeutic Efficacy) Phase III clinical trial. Anti-neutrophil
cytoplasmic auto-antibody (ANCA) -associated vasculitis (AAV). AAV
is a type of rare autoimmune inflammation caused by auto-antibodies
that activate inflammatory cells to attack and destroy the blood
vessels. More than 70 percent of AAV patents exhibit renal disease
manifestations, including progression to end-stage renal disease.
Patients also suffer marked health detriments as a result of
current high dose chronic steroid administration in the established
treatment regimen for AAV. Avacopan successfully completed
two randomized, controlled Phase II clinical trials. Data from
those trials showed that avacopan induced a rapid reduction in
vasculitis severity, led to improved patient reported outcomes, and
allowed elimination of chronic high dose steroids and their
associated deleterious effects.
ADVOCATE is a worldwide study to include up to 200 clinical
sites (of which approximately 180 are presently identified) in 300
patients with newly diagnosed or relapsing AAV. The study
comprises two arms: the therapeutic arm contains 30mg twice-daily
oral doses of avacopan and eliminates corticosteroids, and the
control arm contains a placebo and maintains a standard regimen of
high dose chronic steroids. All patients will also receive a
standard background immunosuppressant, (either cyclophosphamide or
rituximab). Primary endpoints will be measured by Birmingham
Vasculitis Activity Score (BVAS), assessing disease remission at
weeks 26 and 52. Other key endpoints include reduced time to
remission, enhanced quality of life, and decreased
corticosteroid-related toxicities. The ADVOCATE Phase III trial
design was discussed in detail with both the U.S. FDA and European
Medicines Agency (EMA), and agreement was reached on the design and
goals of the trial. ChemoCentryx believes that ADVOCATE, if
successful, should initiate avacopan’s commercial opportunity by
achieving a label in Europe and in the US.
Avacopan: Expansion to Additional Rare Renal Indications
in 2017
The Company’s development plan for avacopan also includes
expanding the drug’s clinical footprint into additional rare renal
diseases. Beyond the ADVOCATE trial in AAV, two additional
development programs are slated for 2017. In the first, the
Company intends to conduct a clinical trial with avacopan in
Complement 3 Glomerulopathy (C3G), a rare renal disease (estimated
at a thousand new cases per year in the US) for which there is no
approved therapy. Encouraging, though limited, data for avacopan in
C3G have already been obtained. Specifically, a C3G patient
has been successfully treated with avacopan administered under a
special protocol in the UK (comparable to compassionate use in the
US), for well over a year. In addition, a clinical trial of
avacopan will be conducted in atypical hemolytic uremic syndrome
(aHUS). The rationale for further studying avacopan in this
indication comes from an ongoing pilot study in aHUS patients,
showing avacopan dosing leads to a marked diminution in the
thrombogenic activity of serum of these patients. In consultation
with regulatory agencies, the Company intends to employ endpoints
of both trials which if successfully met could support registration
of the drug.
“Our aim is to build value for patients and shareholders alike
by bringing forward unique medicines for diseases where treatments
are limited or non-existent,” said Thomas J. Schall, Ph.D.,
President and Chief Executive Officer of ChemoCentryx. “Rare
kidney diseases are not just life-altering, they are
life-threatening. We intend to be a major force in helping
people with rare renal disease, and have built a portfolio of
unique drugs in service of that goal. By incorporating these
novel compounds into a strong kidney health alliance with a highly
experienced renal care partner abroad, we markedly enhance the
potential for clinical adoption and ultimate commercial success of
our programs. We are achieving major steps in our forward
integration plan and value building strategy: moving forward
avacopan into Phase III for AAV, expanding its clinical scope in
C3G and aHUS, and by initiating development with CCX140 in
FSGS.”
Other Programs to be Updated at Medical Conferences This
Year
In addition to anticipated avacopan and CCX140 related medical
conference presentations in 2017, data from the ongoing Phase Ib
study with CCX872, the Company’s second inhibitor of the chemokine
receptor known as CCR2, in patients with advanced pancreatic cancer
will be presented at the 2017 Gastrointestinal Cancers Symposium in
San Francisco, CA on Friday, January 20, 2017.
Financial Update
With the successful closing of two alliances in 2016, the
Company reported proforma September 30, 2016 cash and investments
of approximately $186 million.
Presentation at the 35th Annual J.P. Morgan Healthcare
Conference
Thomas J. Schall, Ph.D., President and Chief Executive Officer,
will present at the 35th Annual J.P. Morgan Healthcare Conference
on Wednesday, January 11, 2017 at 12:00 p.m. PT. A live audio
webcast of the presentation can be accessed through the Investors
section of the Company's website at www.ChemoCentryx.com. A replay
of the webcast will be available on the Company's website for two
weeks following the live presentation.
About Avacopan
Avacopan (CCX168) is an orally-administered small molecule that
is a selective inhibitor of the complement C5a receptor, or C5aR,
and is the lead drug candidate in the Company's orphan and rare
disease program. Avacopan is in Phase III development for
anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated
vasculitis (AAV). Avacopan has successfully completed Phase II
development for the treatment of AAV and appears to be safe, well
tolerated and successful in allowing reduction and elimination of
high-dose steroids, part of standard of care for AAV patients,
while providing effective control of the disease in clinical
studies to date. Avacopan is also in development for the treatment
of atypical hemolytic uremic syndrome (aHUS) and complement 3
glomerulopathy (C3G). The U.S. Food and Drug Administration granted
orphan-drug designation for avacopan for the treatment of patients
with AAV, (which includes Wegener's granulomatosis, microscopic
polyangiitis, and Churg-Strauss syndrome) and also for the
treatment of patients with atypical hemolytic uremic syndrome
(aHUS). The European Commission has granted orphan medicinal
product designation for avacopan for the treatment of microscopic
polyangiitis and granulomatosis with polyangiitis (formerly known
as Wegener's granulomatosis). Both conditions are forms of
AAV. Avacopan was also granted access to the European
Medicines Agency's (EMA) PRIority MEdicines (PRIME) initiative,
which supports accelerated assessment of investigational therapies
addressing unmet medical need.
About CCX140
CCX140 targets the chemokine receptor known as CCR2 and has
successfully completed a Phase II clinical trial in patients with
diabetic nephropathy where it was shown to be safe and well
tolerated while demonstrating statistically significant
improvements in kidney function. CCR2 is found on subsets of
monocytes and macrophages, which are cells of the immune system
believed to play an important role in inflammatory processes.
Blocking CCR2 is intended to reduce the abnormal monocyte- and
macrophage-driven inflammatory response implicated in renal
diseases such as diabetic nephropathy. CCR2 may also have a direct
role in the function of other specialized cells in the kidney,
where its inhibition would correlate with a positive therapeutic
effect.
About ChemoCentryx
ChemoCentryx, Inc. is a clinical-stage biopharmaceutical company
focused on discovering, developing and commercializing
orally-administered therapeutics that target the chemokine and
chemoattractant systems in order to treat autoimmune diseases,
inflammatory disorders and cancer. The chemokine system is a
biological network that regulates inflammation via a collection of
secreted chemokine molecules, or ligands, and their specific cell
surface receptors. Based on its proprietary drug discovery and drug
development platform, ChemoCentryx has generated multiple clinical
and preclinical-stage programs, each targeting distinct chemokine
and chemoattractant receptors with different small molecule
compounds. Avacopan (CCX168), a C5aR inhibitor, is in Phase III
development for the treatment of anti-neutrophil cytoplasmic
auto-antibody-associated vasculitis (AAV). Avacopan has
successfully completed Phase II development for the treatment of
AAV and appears to be safe, well tolerated and successful in
allowing reduction and elimination of high-dose steroids, part of
standard of care for AAV patients, while providing effective
control of the disease in clinical studies to date. Avacopan is
also in Phase II studies for the treatment of atypical hemolytic
uremic syndrome (aHUS). ChemoCentryx has licensed exclusive rights
to Vifor Pharma to commercialize avacopan in Europe and certain
other markets outside of the U.S. and most of Asia. CCX872, a CCR2
inhibitor, successfully completed Phase I development and is in
development for the treatment of non-resectable pancreatic cancer.
CCX140, a distinct CCR2 inhibitor, successfully completed a Phase
II clinical trial where it was shown to be safe and well tolerated
while demonstrating statistically significant improvement in
albuminuria in patients with diabetic nephropathy. ChemoCentryx has
licensed exclusive rights to Vifor Pharma to commercialize CCX140
in markets outside of the U.S. and China. Other clinical programs
include CCX507, a next generation CCR9 inhibitor, which has
successfully completed Phase I development, vercirnon (also known
as Traficet-EN or CCX282) a specific CCR9 inhibitor for the
treatment of inflammatory bowel disease, and CCX354, a CCR1
inhibitor which successfully completed a Phase II clinical trial
for the treatment of rheumatoid arthritis. ChemoCentryx also has
several programs in advanced preclinical development.
Forward-Looking Statements
ChemoCentryx cautions that statements included in this press
release that are not a description of historical facts are
forward-looking statements. Words such as "may," "could," "will,"
"would," "should," "expect," "plan," "anticipate," "believe,"
"estimate," "intend," "predict," "seek," "contemplate,"
"potential," "continue" or "project" or the negative of these terms
or other comparable terminology are intended to identify
forward-looking statements. These statements include the Company's
statements regarding the timing of initiating clinical endpoint
trials of avacopan and CCX140, the enrollment period of the
ADVOCATE Phase III trial, whether the Company’s drug candidates
will be shown to be effective in ongoing or future clinical trials,
what measure may be a registration endpoint in FSGS and whether the
ADVOCATE trial design will enable the drug candidate’s commercial
opportunity. The inclusion of forward-looking statements should not
be regarded as a representation by ChemoCentryx that any of its
plans will be achieved. Actual results may differ from those set
forth in this release due to the risks and uncertainties inherent
in the ChemoCentryx business and other risks described in the
Company's filings with the Securities and Exchange Commission
("SEC"). Investors are cautioned not to place undue reliance on
these forward-looking statements, which speak only as of the date
hereof, and ChemoCentryx undertakes no obligation to revise or
update this news release to reflect events or circumstances after
the date hereof. Further information regarding these and other
risks is included under the heading "Risk Factors" in
ChemoCentryx's periodic reports filed with the SEC, including
ChemoCentryx's Annual Report on Form 10-K filed with the SEC March
14, 2016 and its other reports which are available from the SEC's
website (www.sec.gov) and on ChemoCentryx's website
(www.chemocentryx.com) under the heading "Investors." All
forward-looking statements are qualified in their entirety by this
cautionary statement. This caution is made under the safe harbor
provisions of Section 21E of the Private Securities Litigation
Reform Act of 1995.
Source: ChemoCentryx, Inc.CCXI-G
Contacts:
Susan M. Kanaya
Executive Vice President,
Chief Financial and Administrative Officer
investor@chemocentryx.com
Media:
Denise Powell
denise@redhousecomms.com
510.703.9491
Investors:
Steve Klass, Burns McClellan
212.213.0006
sklass@burnsmc.com
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