CAMBRIDGE, Mass., Sept. 3, 2020 /PRNewswire/ -- Akebia
Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company
with the purpose to better the lives of people impacted by kidney
disease, today announces top-line results from PRO2TECT,
the second of its two global Phase 3 cardiovascular outcomes
programs. The two PRO2TECT studies evaluated
the efficacy and safety of vadadustat, Akebia's investigational
oral hypoxia-inducible factor prolyl hydroxylase inhibitor
(HIF-PHI), versus darbepoetin alfa for the treatment of anemia due
to chronic kidney disease (CKD) in adult patients not on dialysis.
The Company's vadadustat development program also includes two
other global Phase 3 studies (INNO2VATE) for the
treatment of anemia due to CKD in adult patients on dialysis, for
which the Company reported positive top-line data in May.
Vadadustat achieved the primary and key secondary efficacy
endpoint in each of the two PRO2TECT studies,
demonstrating non-inferiority (NI) to darbepoetin alfa as measured
by a mean change in hemoglobin (Hb) between baseline and the
primary evaluation period (weeks 24 to 36) and secondary evaluation
period (weeks 40 to 52). Vadadustat did not meet the primary safety
endpoint of the PRO2TECT program, defined as
non-inferiority of vadadustat versus darbepoetin alfa in time to
first occurrence of major adverse cardiovascular events (MACE),
which is the composite of all-cause mortality, non-fatal myocardial
infarction, and non-fatal stroke across both PRO2TECT
studies.
Akebia is working to present the full dataset from its global
Phase 3 program (INNO2VATE and PRO2TECT) at
an upcoming medical conference and publish the data in peer
reviewed journals. Akebia plans to submit to the U.S. Food and Drug
Administration (FDA) a New Drug Application (NDA) for vadadustat
for the treatment of anemia due to CKD in adult dialysis-dependent
and non-dialysis dependent patients as early as possible in 2021.
Akebia and its collaborator, Otsuka Pharmaceutical Co. Ltd., are
working in close collaboration to prepare a Marketing Authorization
Application (MAA) for submission to the European Medicines Agency
(EMA).
"We remain confident that we have a path toward potential
approval for vadadustat in dialysis supported by positive top-line
results for efficacy and safety from INNO2VATE.
PRO2TECT delivered positive top-line efficacy
results; however, the MACE result presents challenges to achieving
our goal of bringing vadadustat to patients in the non-dialysis
market. While achieving the MACE endpoint would have made our path
here more straightforward, as it is in dialysis, we still believe
we have a path toward approval for vadadustat in non-dialysis,"
stated John P. Butler, President and
Chief Executive Officer of Akebia Therapeutics. "We believe the
cardiovascular safety of vadadustat is supported by the totality of
the data from our global Phase 3 program, including additional
analyses on cardiovascular outcomes observed within key geographic
regions and across certain patient sub-populations within
PRO2TECT."
Butler continued, "With data in hand, we and Otsuka have already
started working on vadadustat's NDA. At this time, we're
planning for a pre-NDA meeting with the FDA before the end of the
year, followed by our NDA filing for both the dialysis and
non-dialysis indications as early as possible next
year. Together with Otsuka, we believe we have an extensive
data package to support the potential approval of vadadustat in
both indications. We look forward to putting this package in front
of health authorities as soon as possible and sharing the full
dataset from our global Phase 3 program at an upcoming medical
conference."
Global Phase 3 PRO2TECT Program
Akebia's
global PRO2TECT program is a cardiovascular
outcomes program that includes two separate Phase 3 studies
(Correction and Conversion), which collectively
enrolled 3,476 adult patients not on dialysis with anemia due to
CKD. Both PRO2TECT studies are global, multicenter,
open label (sponsor blinded), active-controlled (darbepoetin alfa -
an injectable erythropoiesis stimulating agent (ESA)),
non-inferiority studies. In both studies, patients were randomized
1:1 to receive either vadadustat or darbepoetin alfa. Vadadustat
was initiated at a starting oral dose of 300 mg once daily and
adjusted over time in increments of 150 mg within the range of 150
to 600 mg daily using a dose adjustment algorithm, while
darbepoetin alfa was dosed per the U.S. package insert (USPI) or
summary of product characteristics (SmPCs) in appropriate
geographies.
The PRO2TECT Correction study
evaluated 1,751 patients with anemia due to CKD without recent ESA
use (879 and 872 patients randomized to vadadustat and
darbepoetin alfa, respectively). The
PRO2TECT Conversion study evaluated
1,725 patients with anemia due to CKD on an active ESA treatment
(862 and 863 patients randomized to vadadustat and darbepoetin
alfa, respectively).
In both PRO2TECT studies, the primary efficacy
endpoint was the mean change in Hb between baseline and the primary
evaluation period (weeks 24-36). Non-inferiority was achieved if
the lower bound of the 95% confidence interval (CI) for the
between-group difference of the mean Hb change did not fall below
the pre-specified NI margin (-0.75 g/dL). The
PRO2TECT program's primary safety endpoint, MACE,
was independently and blindly assessed by the Brigham and Women's
Hospital's Clinical Endpoint Center (BWH CEC) in Boston, MA, with a comparison of vadadustat to
darbepoetin alfa. MACE is defined as the composite endpoint of
all-cause mortality, non-fatal myocardial infarction, and non-fatal
stroke. To assess MACE, a combined analysis of time to first MACE
event from the two PRO2TECT studies was performed. NI
was achieved if the upper bound of the 95% confidence interval for
the hazard ratio of vadadustat to darbepoetin alfa did not exceed
the pre-specified NI margin of 1.25.
Primary and Key Secondary Efficacy Endpoint
Results
Vadadustat achieved each of the PRO2TECT
studies' primary efficacy endpoints of mean change in Hb between
baseline and the primary evaluation period (mean Hb from weeks 24
to 36) compared to darbepoetin alfa, in adult patients on dialysis,
demonstrating non-inferiority to darbepoetin alfa using an NI
margin of -0.75 g/dL prospectively agreed to with FDA and EMA.
In PRO2TECT's Correction study
(n=1,751):
- Primary Efficacy Endpoint Result: Vadadustat was
non-inferior to darbepoetin alfa. The least square mean difference
in Hb was 0.05 g/dL (95% CI: -0.04, 0.15), achieving the
pre-specified NI criterion of -0.75 g/dL. The mean (SD) Hb level at
week 24 to week 36 was 10.39 (0.99) g/dL for vadadustat-treated
patients compared to 10.35 (1.03) g/dL for darbepoetin alfa-treated
patients.
- Key Secondary Efficacy Endpoint Result: Vadadustat
sustained the target Hb efficacy response at weeks 40 to 52
achieving non-inferiority compared to darbepoetin alfa. The least
square mean difference in Hb was 0.04 g/dL (95% CI: -0.06, 0.14).
The mean (SD) Hb level at week 40 to week 52 was 10.48 (1.05) g/dL
for vadadustat-treated patients compared to 10.45 (1.01) g/dL for
darbepoetin alfa-treated patients.
In PRO2TECT's Conversion study (n=1,725):
- Primary Efficacy Endpoint Result: Vadadustat was
non-inferior to darbepoetin alfa. The least square mean difference
in Hb was -0.01 g/dL (95% CI: -0.09, 0.07), achieving the
pre-specified NI criterion of -0.75 g/dL. The mean (SD) Hb level at
week 24 to week 36 was 10.77 (0.98) g/dL for vadadustat-treated
patients compared to 10.77 (0.99) g/dL for darbepoetin alfa-treated
patients.
- Key Secondary Efficacy Endpoint Result: Vadadustat
sustained efficacy in the Conversion study demonstrating
non-inferiority to darbepoetin with a least square mean difference
in Hb of 0.00 g/dL (95% CI: -0.10, 0.09). The mean (SD) Hb level at
week 40 to week 52 was 10.80 (1.04) g/dL in the vadadustat-treated
patients compared to 10.79 (1.05) g/dL for darbepoetin
alpha-treated patients.
Primary Safety MACE Endpoint Result
The
PRO2TECT program (Correction and
Conversion studies) (n=3,471):
- Primary Safety MACE Endpoint Result:
Vadadustat did not meet the PRO2TECT program's primary
safety endpoint of non-inferiority for MACE. The upper bound of the
95% confidence interval of the Hazard Ratio (HR) was above the
pre-specified NI margin of 1.25 for primary MACE analysis (HR 1.17,
95% CI: 1.01, 1.36). MACE is defined as the composite endpoint of
all-cause mortality, non-fatal myocardial infarction, and non-fatal
stroke.
The incidence of treatment emergent adverse events during the
Correction study in the vadadustat-treated patients was
90.9%, and 91.6% in darbepoetin alfa-treated patients. During the
study, the most common treatment emergent adverse events reported
in vadadustat/darbepoetin alfa-treated patients were end-stage
renal disease (34.7%/ 35.2%), hypertension (17.7%/ 22.1.%),
hyperkalemia (12.3.%/ 15.6%), urinary tract infection (12.9%/
12.0%), diarrhea (13.9%/ 10.0%), peripheral oedema (12.5%/ 10.5%),
fall (9.6%/ 10%) and nausea (10%/ 8.2%). Serious treatment emergent
adverse events were 65.3% for vadadustat-treated patients and 64.5%
for darbepoetin alfa-treated patients. The incidence of treatment
emergent adverse events during the Conversion study in
vadadustat treated patients was 89.1% and 87.7% in darbepoetin
alfa-treated patients. During the study, the most common treatment
emergent adverse events reported in vadadustat/darbepoetin
alfa-treated patients were end-stage renal disease (27.5%/ 28.4%),
hypertension (14.4%/ 14.8%), urinary tract infection (12.2%/
14.5%), diarrhea (13.8.%/ 8.8.%), peripheral oedema (9.9%/ 10.1%)
and pneumonia (10.0%/ 9.7%). Serious treatment emergent adverse
events were 58.5% for vadadustat-treated patients and 56.6% for
darbepoetin alfa-treated patients.
"The results of Akebia's global Phase 3 program continue to
underscore the potential of vadadustat as a once-daily oral
standard of care for patients living with anemia due to CKD, upon
approval," stated Steven K. Burke,
M.D., Senior Vice President, Research & Development and Chief
Medical Officer of Akebia Therapeutics. "There is a significant
unmet medical need among patients living with anemia due to CKD,
and we are excited to be advancing vadadustat as a potential
therapy for these patients. I would like to extend our sincere
thanks to everyone involved in this study, including the patients,
physicians, investigators and their staff."
Investor Conference Call and Live Webcast:
Akebia will
host a conference call with accompanying slides today, Thursday, September 3, 2020, at 8:30 a.m. Eastern Time to discuss the
PRO2TECT data. To listen to the conference call,
please dial (877) 458-0977 (domestic) or (484) 653-6724
(international) using conference ID number 9547389. A live webcast
of the call with accompanying slides can be accessed via the
Investors section of the Company's website
at https://ir.akebia.com/.
A replay of the conference call will be available two hours
after the completion of the call through September 9, 2020. To
access the replay, dial (855) 859-2056 (domestic) or (404) 537-3406
(international) and reference conference ID number 9547389. A
replay of the webcast, and accompanying slides, can be
accessed via the Investors section of the Company's website
at https://ir.akebia.com/.
About Akebia Therapeutics
Akebia Therapeutics, Inc. is
a fully integrated biopharmaceutical company with the purpose to
better the lives of people impacted by kidney disease. The Company
was founded in 2007 and is headquartered in Cambridge, Massachusetts. For more
information, please visit our website at www.akebia.com, which does
not form a part of this release.
About Vadadustat
Vadadustat is an oral
hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor
designed to mimic the physiologic effect of altitude on oxygen
availability. At higher altitudes, the body responds to lower
oxygen availability with stabilization of hypoxia-inducible factor,
which can lead to increased red blood cell production and improved
oxygen delivery to tissues. Vadadustat is in global Phase 3
development for the treatment of anemia due to CKD and is not
approved by the U.S. Food and Drug Administration (FDA) or any
regulatory authority with the exception of Japan's Ministry of Health, Labour and Welfare
(MHLW). In Japan, vadadustat is
approved as a treatment for anemia due to CKD in both
dialysis-dependent and non-dialysis dependent adult patients.
About Anemia due to Chronic Kidney Disease
(CKD)
Anemia is a condition in which a person lacks enough healthy red
blood cells to carry adequate oxygen to the body's tissues. It
commonly occurs in people with CKD because their kidneys do not
produce enough erythropoietin (EPO), a hormone that helps regulate
production of red blood cells. Anemia due to CKD can have a
profound impact on a person's quality of life as it can cause
fatigue, dizziness, shortness of breath and cognitive dysfunction.
Left untreated, anemia leads to deterioration in health and is
associated with increased morbidity and mortality in people with
CKD.
Forward Looking Statements
Statements in this press
release regarding Akebia's strategy, plans, prospects,
expectations, beliefs, intentions and goals are forward-looking
statements within the meaning of the U.S. Private Securities
Litigation Reform Act of 1995, as amended, including but not
limited to statements regarding Akebia's belief that the totality
of the data from its global Phase 3 program for vadadustat supports
the cardiovascular safety of vadadustat, an NDA submission and
marketing approval in both the dialysis and non-dialysis
indications; the path for approval of vadadustat in dialysis and
non-dialysis; the potential challenges with respect to achieving an
approval for vadadustat in the non-dialysis indication; the
assessment of the data from PRO2TECT, including additional
analyses on cardiovascular outcomes observed within key geographic
regions and across certain patient sub-populations; the potential
for marketing approval of vadadustat in dialysis and non-dialysis;
the Company's goal of bringing vadadustat to patients in the
dialysis and non-dialysis markets; the timing of meetings with
regulators, including the pre-NDA meeting with the FDA; safety and
efficacy of vadadustat; the potential indications for and benefits
of vadadustat; sharing vadadustat clinical data, including the full
dataset from INNO2VATE and PRO2TECT, at an upcoming medical
conference, in peer reviewed journals and with health authorities
and others, as well as the timing and forum thereof; submitting
filings for marketing approval of vadadustat, and the timing
thereof; the potential launch and commercialization of vadadustat
if approved by regulatory authorities; and market opportunity,
clinical opportunity, commercial potential, prevalence, and the
growth in, and potential demand for, vadadustat. The terms
"advance," "believe," "goal," "look forward," "opportunity,"
"planned," "potential," "will" and similar references are intended
to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Each
forward-looking statement is subject to risks and uncertainties
that could cause actual results to differ materially from those
expressed or implied in such statement, including the timing and
content of advice given and decisions made by health authorities,
including marketing approval and labeling decisions; the actual
time it takes to make regulatory submissions for vadadustat to
health authorities, including the submission of the NDA to the FDA
and the MAA to EMA; risks associated with the Priority Review
Voucher for vadadustat; the potential direct or indirect impact of
the COVID-19 pandemic on our business, operations, and the markets
and communities in which we and our partners, collaborators,
vendors and customers operate; manufacturing and quality risks;
risks associated with management and key personnel changes and
transitional periods; the actual funding required to continue to
commercialize our commercial product, develop and commercialize
vadadustat and operate the Company; market acceptance and coverage
and reimbursement of our commercial product and vadadustat, if
approved; the risks associated with potential generic entrants for
our commercial product and vadadustat, if approved; early
termination of any of Akebia's collaborations; Akebia's and its
collaborators' ability to satisfy their obligations under Akebia's
collaboration agreements; the competitive landscape for our
commercial product and vadadustat; the scope, timing, and outcome
of any legal, regulatory and administrative proceedings; changes in
the economic and financial conditions of the businesses of Akebia
and its partners; and Akebia's ability to obtain, maintain and
enforce patent and other intellectual property protection for our
commercial product, vadadustat and any other product candidates.
Other risks and uncertainties include those identified under the
heading "Risk Factors" in Akebia's Quarterly Report on Form 10-Q
for the quarter ended June 30, 2020
and other filings that Akebia may make with the U.S. Securities and
Exchange Commission in the future. These forward-looking statements
(except as otherwise noted) speak only as of the date of this press
release, and Akebia does not undertake, and specifically disclaims,
any obligation to update any forward-looking statements contained
in this press release.
Investor Contact:
Kristen K. Sheppard, Esq.
Ir@akebia.com
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