ChemoCentryx Announces Positive Top-Line CCX168 Phase II Data in
ANCA-Associated Renal Vasculitis
Company Also Provides Update on GSK Partnership Programs
Conference Call and Slide Presentation Webcast Scheduled Today at 5:00pm ET /
MOUNTAIN VIEW, Calif., Dec. 3, 2013 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc.,
(Nasdaq:CCXI), today announced positive top-line data from the first two steps
of a Phase II trial with CCX168, an inhibitor targeting the chemoattractant
receptor known as C5aR, in anti-neutrophil cytoplasmic antibody
(ANCA)-associated renal vasculitis (AARV). AARV is a serious autoimmune
disease causing inflammation of the smaller blood vessels. If left untreated,
the disease can be fatal. Data from the first two steps of the C5aR inhibitor
on Leukocytes Exploratory ANCA-associated Renal Vasculitis (CLEAR) trial are
promising, demonstrating that CCX168 appears to be safe, well tolerated and
successful in allowing both reduction and elimination of high-dose
corticosteroids, part of standard of care for AARV patients, without
compromising efficacy or safety during a 12-week treatment period. There were
no unexpected serious adverse events reported by patients taking CCX168.
Furthermore, CCX168 treatment showed greater improvements consistently across
a number of renal health parameters, including renal remission, albuminuria
and Birmingham Vasculitis Activity Score (BVAS), compared to standard of care
treatment (see table below). Detailed results from the study will be presented
at upcoming major medical meetings. Under the terms of an alliance with
GlaxoSmithKline (GSK) established in August 2006, GSK has declined its option
to license CCX168. Accordingly, ChemoCentryx plans to expand the clinical
development program for CCX168, and will retain full development and
commercial rights to the C5aR program.
"The major unmet needs in AARV treatment are improvements in safety,
especially by reducing glucocorticoid exposure, and reducing the time taken to
achieve disease control. These Phase II data show encouraging signs that
treatment with CCX168 both enabled a reduction in glucocorticoid exposure, and
improved the speed and quality of remission," said David Jayne, MD, FRCP,
Director, Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK
and Principal Investigator of the study. "These results were achieved without
an adverse event signal attributable to CCX168, and if confirmed in larger
studies, suggest that CCX168 has the potential to become a routine component
of AARV induction regimens."
"Given the Phase II results to date and toxicities associated with current
treatment options for AARV patients, we intend to file applications for both
Breakthrough Therapy and Orphan Drug Designations with the FDA, in hopes of
optimizing efficiency of development of CCX168 and bringing this therapy to
patients as rapidly as possible. Pending discussions with FDA and key opinion
leaders, our hope is that we could initiate a Phase III program in 2014," said
Thomas Schall, PhD, President and Chief Executive Officer, of ChemoCentryx.
"CCX168 is a leading asset in our pipeline, and along with CCX140, our CCR2
inhibitor in a Phase II trial for diabetic nephropathy, anchors the renal
disease portfolio wholly owned by the Company."
CCX168 + CYC+ Standard of
Parameter Low-Dose CCX168 + CYC + Care:
Steroids No Steroids CYC + High-Dose
(N=8) (N=8) Steroids
Steroid rescue events during 0 1 (13%) 1 (11%)
12-week treatment period
Renal remission at 12 weeks* 75% 63% 44%
U-ACR geometric mean % change at -63% -59% -9%
eGFR mean change at 12 weeks 6.8 0.6 2.2
Urinary MCP-1:creatinine ratio
geometric mean % change at 12 -72% -52% -37%
*Renal remission is defined as a reduction from baseline in urinary RBCs plus
improvement in renal function based on eGFR;
U-ACR = urinary albumin:creatinine ratio;
eGFR = estimated glomerular filtration rate;
MCP-1 = monocyte chemoattractant protein-1;
CYC = cyclophosphamide
No unexpected serious adverse events were observed with CCX168 use in the
One subject withdrew early from the control group.
A total of 26 patients with newly diagnosed or relapsed ANCA-associated renal
vasculitis were enrolled in the CLEAR trial, which was conducted at 38 sites
throughout Europe. All patients were treated with background cyclophosphamide
of 15 mg/kg administered intravenously every two to three weeks.
In Step 1, 12 patients were randomized 2:1 to either 30 mg of oral CCX168 BID
or placebo over a 12-week treatment period. In addition, the CCX168 group (n=8
patients) received a 20 mg starting dose ("low dose") of prednisone, while the
placebo group (n=4 patients) received a 60 mg starting dose of prednisone
("high dose"), the standard of care.
In Step 2, 14 patients were also randomized 2:1 to either 30 mg BID of oral
CCX168 BID or placebo over a 12-week treatment period. The CCX168 group (n=8
patients) received no prednisone, while the placebo group (n= 6 patients)
received a 60 mg starting dose of high-dose prednisone.
The primary goal of the first two steps of the Phase II trial was to determine
whether CCX168 could safely reduce or eliminate the use of corticosteroids
during treatment of patients experiencing a renal disease flare. Since safety
consequences of high-dose steroids, such as serious infections, are of major
concern, the objective was to evaluate whether the efficacy with CCX168, as a
replacement for steroids, is at least comparable to high-dose steroids in
patients receiving background cyclophosphamide treatment. Safety and efficacy
measurements include incidence of steroid rescue treatment, renal remission
and other renal markers as well as global vasculitis disease activity, as
measured by Birmingham Vasculitis Activity Score (BVAS).
CCR1 Program Update
In other partnership news, GSK has returned to ChemoCentryx all rights to
CCX354 (GSK2941266), an inhibitor of the chemokine receptor known as CCR1, for
all indications, including rheumatoid arthritis. With the return of this last
program under the alliance with GSK, no active research programs remain under
the alliance.As such, the August 2006 product development and
commercialization agreement established between the two companies has ended.
"We thank GSK for the support and collaboration it has provided ChemoCentryx
during the term of our alliance," said Markus J. Cappel, Chief Business
Officer of ChemoCentryx."We continue to have a keen interest in the CCR1
program based on our proof-of-concept CARAT-2 clinical trial with CCX354 in
rheumatoid arthritis and through our de novo discovery efforts. We have
identified a more potent next generation series of CCR1 inhibitors that are
complementary to CCX354 and serve to bolster our CCR1 program."
Conference Call and Webcast
The Company will host a conference call and webcast today,December 3, 2013,
at5:00 p.m. Eastern Time / 2:00 p.m. Pacific Timeto discuss these results
and to answer questions.
A slide presentation will accompany the call and can be accessed under "Events
and Presentations" in the Investors section of the Company's website at
www.chemocentryx.com. Please log in approximately 5-10 minutes before the
call to ensure a timely connection.
To participate by telephone, please dial (877) 303-8028 (Domestic) or(760)
536-5167(International). The conference ID number is 19772739.
A live and archived webcast can be accessed through the Investors section of
the Company's website athttp://www.chemocentryx.comand will remain available
for fourteen (14) days following the call.
About CCX168 and ANCA-Associated Renal Vasculitis
ANCA-associated renal vasculitis is a specific type of auto-immune
inflammation that causes leaking of blood and protein into the urine, and can
lead to kidney failure, if left untreated. The morbidity and mortality remains
high, with many patients suffering severe adverse effects of treatment.
Current therapy causes severe adverse events in 25% of patients in the first
year, irreversible damage in over 50% and is the major cause of death in the
first 5 years.There is a need for safer, more effective therapy.
An estimated 10 to 20 per 1 million people are affected by AARV annually in
the U.S. ANCA-associated renal vasculitis is observed in patients clinically
diagnosed with granulomatosis with polyangiitis (previously called Wegener's
granulomatosis), microscopic polyangiitis or renal limited vasculitis.
CCX168 targets the chemo-attractant C5a receptor, or C5aR, which binds to a
biologically activated fragment of the complement protein known as C5a. C5aR
is thought to play a role in a range of inflammatory and autoimmune diseases,
About CCX354 and Rheumatoid Arthritis (RA)
CCX354 (GSK2941266) is a potent and selective antagonist of CCR1, a chemokine
receptor that drives the recruitment of certain inflammatory cells including
populations of monocytes, macrophages and T cells into the joints of patients
with RA.By selectively blocking the CCR1 receptor, CCX354 is designed to
reduce the infiltration of inflammatory cells into the joints of RA patients,
thus inhibiting the inflammation, swelling, pain and associated joint
destruction while minimizing the potential for off-target effects. RA is
estimated to affect more than two million people in the U.S. and is a leading
cause of morbidity, disability and reduced work ability. The exact cause of RA
is unknown, but is believed to reflect the body's immune system attack on the
synovium, the tissue that lines the joints. Despite available treatments,
there remains a significant unmet medical need for better therapies for RA.
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. Vercirnon (also known as Traficet-EN or
CCX282) is a specific CCR9 inhibitor for the treatment of inflammatory bowel
disease. CCX140, a CCR2 inhibitor, has been shown to be safe and well
tolerated while demonstrating clinical activity on glycemic indices in a Phase
II clinical trial in type 2 diabetics, and is now in Phase II clinical
development for the treatment of diabetic nephropathy. Other clinical programs
include CCX168, a C5aR inhibitor in Phase II clinical development for the
treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated renal
vasculitis, CCX354, a CCR1 inhibitor which successfully completed a Phase II
clinical trial for the treatment of rheumatoid arthritis, as well as CCX872, a
CCR2 inhibitor, and CCX507, an inhibitor of CCR9, both of which are in Phase I
clinical testing. ChemoCentryx also has several programs in advanced
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" or "continue" or the negative of these terms or
other comparable terminology are intended to identify forward-looking
statements. These statements are based on the Company's current beliefs and
expectations and include the Company's statements regarding its expectations
as to whether and when it will be able to file for breakthrough therapy and
orphan drug status with the FDA for CCX168 and the timing of the Company's
proposed clinical trials. 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 for the year ended
December 31, 2012 and ChemoCentryx's Quarterly Report on Form 10-Q for the
three-month period ended September 30, 2013, which are available from the
SEC's website (www.sec.gov) and are also available from 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.
CCXI - G
CONTACT: Susan M. Kanaya
Senior Vice President, Finance and
Chief Financial Officer
Markus J. Cappel, Ph.D.
Chief Business Officer
ChemoCentryx, Inc. logo
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