ChemoCentryx, Inc. and Vifor Fresenius Medical Care Renal Pharma
(VFMCRP) today announced topline data from the ACCOLADE clinical
study, the largest, randomized, blinded, placebo-controlled trial
in the ultra-rare kidney disease C3 Glomerulopathy (C3G) to date,
which evaluated avacopan for the treatment of that disorder.
Avacopan is a first-in-class, orally-administered selective
inhibitor of the complement C5a receptor.
Patients in the multi-center ACCOLADE clinical trial were
randomized to receive either 30mg of avacopan twice daily (BID) or
placebo for 26 weeks in a double-blind manner. The primary endpoint
of the study was defined as the change from baseline in the C3G
Histologic Index for Disease Activity, as determined by a blinded
analysis of kidney biopsies taken at baseline and after 26 weeks of
blinded study treatment. Pre-specified secondary endpoints included
changes in the estimated Glomerular Filtration Rate (eGFR) (a
validated measure of overall renal function), measurement of
urinary protein to creatinine ratio (UPCR), measurements of urinary
MCP-1 (a marker of kidney inflammation), and the C3G Histologic
Index for Disease Chronicity, a biopsy based measure of the
progression of renal fibrosis which is a strong predictor for
progression to end stage renal disease (ESRD) in C3G. After the
initial blinded treatment period, all patients receive avacopan as
part of an open label extension for a further 26 weeks. Endpoint
determinations from the blinded treatment period (baseline to week
26) are presented.
“The ultra-rare disease, C3 glomerulopathy, is a progressive
kidney disorder where a person’s renal function inexorably
declines, where we have no approved therapy, and also no clear
roadmap on how to get to an approved therapy,” said Thomas J.
Schall, President and Chief Executive Officer of ChemoCentryx. “The
data from this well-controlled, blinded placebo comparison trial
provides evidence that avacopan can improve kidney function in C3G.
Recall that avacopan also improved kidney function in
ANCA-associated vasculitis; here again the ACCOLADE C3G data show a
robust and significant increase in eGFR after 26 weeks of therapy.
While eGFR was a pre-specified secondary endpoint, few experts
would have advised that such an increase would or could be
demonstrated in this time frame in a trial of this size. It is
notable too that although our chosen primary (but unvalidated) C3G
histologic index for disease activity endpoint was not entirely
informative in ACCOLADE, the significant improvement in renal
function demonstrated with avacopan in C3G is indeed remarkable and
promising. For patients, this could mean markedly slowing or even
halting kidney decline, with slower progression to dialysis or
transplant. We will discuss our present data with the FDA to gain
their input as to the possibility of a license in this very rare
and otherwise inadequately treated disorder.”
“We are pleased with the results of the ACCOLADE study,” said
Stefan Schulze, Chief Executive Officer of Vifor Pharma. “This data
set is encouraging, demonstrating important clinical benefits in
patients with this C3G kidney disease in which there is currently
no approved therapy. The study further consolidates the
effectiveness of avacopan in proliferative glomerular diseases and
provides more evidence for the safety profile of avacopan. VFMCRP
will commence discussions with the European regulatory authorities
about the best possible regulatory pathway to obtain approval for
the European Patients in this rare and otherwise inadequately
treated disease.”
Study Readouts
The primary endpoint of the study was change from baseline to
week 26 in the C3G Histologic Index for Disease Activity1,
comparing the changes in kidney histology from biopsy sections
taken from patients characterized by elevated levels of C5b-9
complement markers in the blood at time of study entry (baseline).
Biopsies, taken at baseline and after 26 weeks of treatment showed
that the placebo group worsened by 38% on average in the C3G
Activity Score while the avacopan group improved by 2% on average.
This approximately 40% average difference between the two treatment
arms did not constitute statistical significance due to the high
patient to patient variability. Comparison of the C3G Activity
Score of all C3G subjects (comprising those with both elevated
levels of C5b-9 as well as those with normal levels of C5b-9)
yielded similar results: the placebo group worsened by 26% on
average in the C3G Activity Score, while avacopan therapy resulted
in an improvement of 6% on average.
Importantly, those patients who received avacopan experienced
significant benefits in terms of kidney function and other
parameters compared to those who received placebo. These benefits,
assessed as pre-specified secondary endpoints, include:
Slowing of Fibrosis Progression
Avacopan therapy demonstrated evidence for a significant slowing
of the progression of fibrosis as assessed by the C3G Histologic
Index for Disease Chronicity. The placebo group overall exhibited a
26 percentage point higher change from baseline to Week 26 in the
C3G Index for Disease Chronicity than avacopan (58% versus 32%,
respectively) representing a worsening in disease chronicity. The
mean change from baseline to week 26 was 1.6 for placebo versus 0.8
for avacopan (P<0.05). The avacopan-related lower increase is
notable because published literature shows that each 1-unit
increase in C3G Histologic Index for Disease Chronicity from
baseline increases by 59% (P < 0.001) the risk of doubling of
creatinine, progression to chronic kidney disease stage 5, ESRD
requiring dialysis or transplantation, or death.1
Improvement in Kidney Function
The avacopan group demonstrated a statistically significant
improvement in eGFR from baseline to week 26. Overall, the eGFR in
the avacopan group improved 5% on average from baseline while the
placebo group worsened by 6% (P = 0.0221). Renal improvement was
particularly pronounced for C3G subjects with eGFR of < 60
mL/min/1.73 m2 at baseline, as their eGFR on average increased
relative to placebo by nearly 20% after 26 weeks (13% improvement
for avacopan versus 6% worsening from baseline for placebo, P =
0.0199). This was equivalent to a mean increase of about 5
mL/min/1.73 m2 on avacopan versus a decrease of 1.4 mL/min/1.73 m2
in the placebo group. Significant improvement in eGFR in a blinded
comparative setting over 26 weeks has not been noted in C3G studies
prior to this, but the improvement in eGFR with avacopan is
reminiscent of a similar improvement seen with avacopan therapy in
ANCA–associated vasculitis with renal dysfunction.
Other measures of kidney function include UPCR (proteinuria),
where high UPCR is known to be associated with higher risk of ESRD
in C3G as well as other renal diseases, and urinary MCP-1
creatinine ratio, a marker of glomerular inflammation.
In the ACCOLADE study, avacopan therapy was associated with a
rapid reduction in UPCR (proteinuria). From baseline, a progressive
proteinuria drop was seen in the avacopan group: at week 16 there
was a 35% mean decrease in UPCR with avacopan versus a 1% decrease
in the placebo group (P < 0.05), and at the end of 26 weeks UPCR
was reduced by 26% in the avacopan group versus 14% in the placebo
group.
Similar reductions were seen in urinary MCP-1 creatinine ratio
in the avacopan group versus the placebo group throughout the
26-week treatment period, with the avacopan group consistently
exhibiting lower levels of the kidney inflammation marker being
shed in the urine.
Avacopan also appeared safe and well-tolerated in patients with
C3G.
In the ongoing phase of the study (after the 26 week blinded
treatment period), all patients receive avacopan as part of an open
label extension for a further 26 weeks, and are followed for an
additional 8 weeks without study treatment. Data from the open
label and follow up period will be analyzed and presented at a
future time.
Based on the data described above, reflecting results of a
blinded therapy regimen which resulted in evidence of avacopan’s
ability to improve renal function, being well-tolerated in C3G
patients to date, and the significant unmet medical need for C3G
patients for whom there are no approved therapies to treat renal
function decline, ChemoCentryx plans to discuss the results with
the U.S. Food and Drug Administration.
- Bomback AS, et al. C3 glomerulonephritis and dense deposit
disease share a similar disease course in a large United States
cohort of patients with C3 glomerulopathy. Kidney Int. 2018.
Conference Call and WebcastChemoCentryx will
host a conference call and webcast today, December 21,
2020 at 4:30 p.m. Eastern Time / 1:30 p.m.
Pacific Time. To participate by telephone, please dial (877)
303-8028 (Domestic) or (760) 536-5167 (International). The
conference ID number is 9519489. A live and archived audio webcast
can be accessed through the Investors section of the Company's
website at www.ChemoCentryx.com. The archived webcast will
remain available on the Company's website for fourteen (14) days
following the conference call.
|
Contact
and further information: |
|
|
|
Media RelationsNathalie PonnierGlobal Head
Corporate Communications+41 79 957 96 73 media@viforpharma.com |
Investor RelationsJulien Vignot Head of Investor
Relations+41 58 851 66 90investors@viforpharma.com |
|
|
|
|
ChemoCentryx Contacts: |
|
|
Susan M.
Kanaya |
|
|
Executive Vice President |
|
|
Chief
Financial and Administrative Officer |
|
|
investor@chemocentryx.com |
|
|
|
|
|
Media: |
Investors: |
|
Stephanie Tomei |
Lee
Roth, Burns McClellan |
|
408.234.1279 |
212.213.0006 |
|
media@chemocentryx.com |
lroth@burnsmc.com |
|
|
|
|
Vifor Pharma Group is a global pharmaceuticals
company. It aims to become the global leader in iron deficiency,
nephrology and cardio-renal therapies. The company is a partner of
choice for pharmaceuticals and innovative patient-focused
solutions. Vifor Pharma Group strives to help patients around the
world with severe and chronic diseases lead better, healthier
lives. The company develops, manufactures and markets
pharmaceutical products for precision patient care. Vifor Pharma
Group holds a leading position in all its core business activities
and consists of the following companies: Vifor Pharma and Vifor
Fresenius Medical Care Renal Pharma (a joint company with Fresenius
Medical Care). Vifor Pharma Group is headquartered in Switzerland,
and listed on the Swiss Stock Exchange (SIX Swiss Exchange, VIFN,
ISIN: CH0364749348). For more information, please visit
viforpharma.com
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.
Besides ChemoCentryx’s lead drug candidate, avacopan,
ChemoCentryx also has early stage drug candidates that target
chemoattractant receptors in other inflammatory and autoimmune
diseases and in cancer.About C3 Glomerulopathy and the
ACCOLADE Trial
Complement 3 Glomerulopathy (C3G) is a very rare, potentially
progressive kidney disease which can present in patients of all
ages, including children. It is diagnosed on kidney biopsy
performed because the patient has kidney impairment, hematuria
and/or loss of protein into the kidneys. Treatment is challenging
and there is no approved drug with proven benefit so patients are
at risk of progression to End Stage Renal Disease (ESRD). 30-50%
will progress to ESRD within 10 years of diagnosis. The complement
system is dysregulated in C3G with various mutations and acquired
factors in different patient groups. These can be assessed in
specialist centers and may be helpful in understanding treatment
approaches and risk of ESRD.
The Phase II ACCOLADE clinical trial randomized patients with
C3G to avacopan or placebo. The pre-specified primary endpoint
assesses 30 mg BID of avacopan against placebo at 26 weeks of
treatment, using the C3G Histologic Index – this is an index
assessing acute and chronic damage in the kidney. Pre-specified
secondary endpoints include stabilization in disease chronicity,
reduction in proteinuria, changes or improvement in renal function
and quality of life.
Following the 26-week double-blind treatment period, all
patients receive avacopan for a further 26 weeks. Patients are
followed for an additional 8 weeks for assessment of safety and
efficacy.
The U.S. Food and Drug Administration has granted avacopan
orphan drug designation for C3G, and the European Commission has
granted orphan medicinal product designation for avacopan for
C3G.
About AvacopanAvacopan is an
orally-administered small molecule that is a selective inhibitor of
the complement C5a receptor C5aR1. By precisely blocking the
receptor (the C5aR) for the pro-inflammatory complement system
fragment, 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 inflammation. Moreover, avacopan’s selective inhibition
of only the C5aR1 leaves the beneficial C5a l pathway through the
C5L2 receptor functioning normally.ChemoCentryx is also developing
avacopan for the treatment of patients with anti-neutrophil
cytoplasmic antibody-associated vasculitis (ANCA-associated
vasculitis or ANCA vasculitis) and hidradenitis suppurativa (HS).
The U.S. Food and Drug Administration has granted avacopan
orphan-drug designation for ANCA-associated Vasculitis, C3G and
atypical hemolytic uremic syndrome. The European Commission has
granted orphan medicinal product designation for avacopan for the
treatment of two forms of ANCA Vasculitis: microscopic polyangiitis
and granulomatosis with polyangiitis (formerly known as Wegener's
granulomatosis), as well as for C3G. In November 2020, European
Medicines Agency (EMA) accepted to review the Marketing
Authorization Application (MAA) for avacopan for the treatment of
patients with ANCA-associated vasculitis (granulomatosis with
polyangitis (GPA) and microscopic polyangiitis (MPA)).
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 achievement of
anticipated goals and milestones, whether there is a regulatory
path forward for avacopan in the treatment of C3 glomerulopathy 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.
ChemoCentryx (NASDAQ:CCXI)
Historical Stock Chart
From Aug 2024 to Sep 2024
ChemoCentryx (NASDAQ:CCXI)
Historical Stock Chart
From Sep 2023 to Sep 2024