ChemoCentryx, Inc., (Nasdaq: CCXI), today announced that The New
England Journal of Medicine (NEJM) has published results from
ADVOCATE, the pivotal Phase III study evaluating avacopan, an
orally-administered selective complement 5a receptor inhibitor, for
the treatment of patients with anti-neutrophil cytoplasmic
autoantibody-associated vasculitis (ANCA-associated vasculitis or
ANCA vasculitis). The publication also featured an editorial
titled, “Avacopan — Time to Replace Glucocorticoids?” written by
Kenneth J. Warrington, M.D., Chair in the Division of Rheumatology,
Department of Internal Medicine at Mayo Clinic in Rochester, Minn.
ANCA-associated vasculitis is a systemic auto-immune disease in
which over-activation of the complement system further activates
neutrophils, leading to inflammation and eventual destruction of
small blood vessels. This results in organ damage and failure, with
the kidney as the major target, and is fatal if not treated.
“The results of the ADVOCATE trial are transformational and
demonstrate the potential of avacopan to offer a substantial change
in the treatment paradigm for ANCA-associated vasculitis,” said
Peter A. Merkel, M.D., MPH, Chief of Rheumatology and Professor of
Medicine and Epidemiology at the University of Pennsylvania.
“Current treatment for ANCA-associated vasculitis consists of
combining months of daily glucocorticoids (“steroids” such as
prednisone) with other immunosuppressive medications. Use of
prednisone is associated with significant side-effects, including
infections, diabetes mellitus, weight gain, and other problems. The
ability of avacopan to replace prednisone and help patients achieve
sustained remission is a significant and exciting advance for the
treatment of patients with ANCA-associated vasculitis.”
“The ADVOCATE trial clearly demonstrates avacopan’s ability to
improve kidney function, measured by eGFR, in ANCA-associated
vasculitis, and was recently reinforced in another orphan kidney
disease, C3 Glomerulopathy. This is a significant advantage over
other treatment options that often come with added toxicities
and will likely lead to reduced risk
of kidney failure over the longer term,” said David
Jayne, M.D., Director of the Vasculitis and Lupus Service,
Addenbrooke’s Hospital in Cambridge.
The ADVOCATE trial was a global, randomized, double-blind,
active-controlled, double-dummy Phase III trial in 331 patients
with ANCA-associated vasculitis in 20 countries. Eligible patients
were randomized to receive either avacopan or oral prednisone. In
addition, all patients received standard background therapy of
either: (a) rituximab for 4 weeks; or (b) cyclophosphamide for 13
weeks followed by azathioprine/mycophenolate, evenly balanced
between the avacopan and prednisone groups.
The study met both of its primary endpoints, demonstrating
disease remission at 26 weeks and sustained remission at 52 weeks,
as assessed by the Birmingham Vasculitis Activity Score (BVAS).
Specifically, BVAS remission at week 26 was achieved in 72.3% of
the avacopan treated patients vs. 70.1% of subjects in the
prednisone group (p<0.0001 for non-inferiority). Sustained
remission at 52 weeks was observed in 65.7% of the avacopan treated
subjects vs. 54.9% in the prednisone group, achieving both
non-inferiority and superiority to the prednisone group (p=0.007
for superiority of avacopan).
Additionally, results published in the NEJM also show that,
compared to the prednisone group, avacopan treatment:
- Reduced the risk
of vasculitis relapse by 54%; there was a 10.1% relapse rate in the
avacopan group compared to 21.0% in the prednisone group.
- Demonstrated
greater improvement in kidney function, with a mean increase from
baseline to week 52 in estimated glomerular filtration rate (eGFR)
of 7.3 mL/min/1.73 m2 with avacopan therapy vs. an increase in eGFR
of 4.1 mL/min/1.73 m2 in the prednisone group, and the difference
between groups was 3.2 mL/min/1.73 m2 (95% CI, 0.3 to 6.1).
- Significantly
lowered glucocorticoid toxicity, with avacopan therapy 39.7 vs.
56.6 in the prednisone group in the Glucocorticoid Toxicity Index
(GTI) Cumulative Worsening Score with a difference between groups
of −16.8 points (95% CI, −25.6 to −8.0), and 11.2 with avacopan
therapy vs. 23.4 for the prednisone group in the GTI Aggregate
Improvement Score, with a difference between groups of −12.1 points
(95% CI, −21.1 to −3.2).
- Led to greater
improvement in health-related quality of life, measured by the
Short Form 36 (SF-36) version 2 and the EuroQOL-5D-5L instrument
(both Visual Analogue Scale and EQ Index), compared to the
prednisone group.
Avacopan demonstrated favorable safety results in this serious
and life-threatening disease, with fewer subjects having serious
adverse events in the avacopan group than in the prednisone
group.
The U.S. Food and Drug Administration (FDA) is evaluating
avacopan for the treatment of ANCA-associated vasculitis and has
set a Prescription Drug User Fee Act (PDUFA) target goal date of
July 7, 2021.
About ADVOCATE and ANCA-Associated
VasculitisThe ADVOCATE trial of avacopan was a global,
randomized, double-blind, active-controlled, double-dummy Phase III
trial of 331 patients with ANCA-associated vasculitis in 20
countries. Eligible study subjects were randomized to receive
avacopan plus either rituximab or cyclophosphamide (followed by
azathioprine/mycophenolate) or prednisone plus either rituximab or
cyclophosphamide (followed by azathioprine/mycophenolate).
ANCA-associated vasculitis is a systemic disease in which
over-activation of the complement pathway further activates
neutrophils, leading to inflammation and destruction of small blood
vessels. This results in organ damage and failure, with the kidney
as the major target, and is fatal if not treated. Currently,
treatment for ANCA-associated vasculitis consists of courses of
non-specific immuno-suppressants (cyclophosphamide or rituximab),
combined with the administration of daily glucocorticoids
(steroids) for prolonged periods of time, which can be associated
with significant clinical risk including death from infection.
About AvacopanAvacopan is a first-in-class,
orally-administered small molecule that employs a novel, highly
targeted mode of action in the treatment of ANCA-associated
vasculitis and other complement-driven autoimmune and inflammatory
diseases. By precisely blocking the receptor (the C5aR) for the
pro-inflammatory complement system fragment known as C5a on
destructive inflammatory cells such as blood neutrophils, avacopan
arrests the ability of those cells to do damage in response to C5a
activation, which is known to be the driver of ANCA-associated
vasculitis. Current therapies for ANCA-associated vasculitis and
other related illnesses typically include broad immunosuppression
with daily doses of glucocorticoids (steroids) such as prednisone
or methylprednisone, which can cause significant illness and even
death. Avacopan therapy was designed to prevent these outcomes.
Moreover, avacopan’s selective inhibition of only the C5aR leaves
the beneficial C5a pathway through the C5L2 receptor functioning
normally.
The U.S. Food and Drug Administration (FDA) is evaluating a New
Drug Application (NDA) for avacopan for the treatment of
ANCA-associated vasculitis and has set a Prescription Drug User Fee
Act (PDUFA) goal date of July 7, 2021.
ChemoCentryx is also developing avacopan for the treatment of
patients with C3 glomerulopathy (C3G) and severe hidradenitis
suppurativa (HS). The U.S. Food and Drug Administration has granted
avacopan orphan drug designation for ANCA-associated vasculitis and
C3G. The European Commission has granted orphan medicinal product
designation for avacopan for the treatment of two forms of
ANCA-associated vasculitis: microscopic polyangiitis and
granulomatosis with polyangiitis (formerly known as Wegener's
granulomatosis), as well as for C3G.
ChemoCentryx's Kidney Health Alliance with Vifor Pharma provides
Vifor Pharma with exclusive rights to commercialize avacopan in
markets outside of the U.S.
About ChemoCentryxChemoCentryx is a
biopharmaceutical company developing new medications for
inflammatory and autoimmune diseases and cancer. ChemoCentryx
targets the chemokine and chemoattractant systems to discover,
develop and commercialize orally-administered therapies.
ChemoCentryx’s lead drug candidate, avacopan (CCX168), successfully
completed a pivotal Phase III trial in ANCA-associated vasculitis
and a New Drug Application is under review by the U.S. Food and
Drug Administration. Avacopan is also in late stage clinical
development for the treatment of severe Hidradenitis Suppurativa
and C3 glomerulopathy (C3G).
ChemoCentryx also has early stage drug candidates that target
chemoattractant receptors in other inflammatory and autoimmune
diseases and in cancer.
Forward-Looking StatementsChemoCentryx 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
anticipated PDUFA date for the avacopan NDA for the treatment of
ANCA-associated vasculitis, the achievement of anticipated goals
and milestones, whether avacopan will be approved by the FDA or EMA
for the treatment of ANCA-associated vasculitis, whether avacopan
will be an effective treatment in other indications such as C3G or
severe HS, and whether the Company's drug candidates will be shown
to be effective in ongoing or future 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 filed with the SEC on March 10, 2020 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.
Contacts:Susan M. KanayaExecutive Vice
President,Chief Financial and Administrative
Officerinvestor@chemocentryx.com
Media:Stephanie
Tomei408.234.1279media@chemocentryx.com
Investors:Burns McClellan, Inc.Lee
Roth212.213.0006lroth@burnsmc.com
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