Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa,
Ph.D., “Astellas”) and FibroGen, Inc. (Nasdaq: FGEN, CEO: Thomas B.
Neff, “FibroGen”) today announced the presentation of data from two
Japanese Phase 3 studies (1517-CL-0302 and 1517-CL-0307) of
roxadustat (development code: ASP1517/FG-4592) for the treatment of
anemia associated with Chronic Kidney Disease (CKD) in patients on
dialysis at the American Society of Nephrology (ASN) Kidney Week
2018 that was held October 23 – 28, 2018 in San Diego, California.
The 1517-CL-0302 study evaluated the efficacy
and safety of roxadustat in Japanese CKD patients on peritoneal
dialysis (PD). In this study, roxadustat was well tolerated and
achieved and maintained hemoglobin (Hb) levels within the target
range in Japanese CKD patients on PD, with or without previous
treatment with erythropoiesis-stimulating agents (ESAs). The
1517-CL-0307 study evaluated the efficacy and safety of roxadustat
compared to darbepoetin alfa (genetical recombination)
(“darbepoetin alfa”) in the treatment of CKD anemia in patients on
hemodialysis (HD) who had previously been treated with recombinant
human erythropoietin (rHuEPO) or darbepoetin alfa. In this study,
roxadustat effectively maintained Hb within the range of 10-12 g/dL
in HD patients, and its efficacy was non-inferior to darbepoetin
alfa. In both studies, the safety profile of roxadustat was
consistent with previous studies in the CKD population.
“Anemia, a common complication of CKD, is
associated with significant morbidity and mortality, and the
condition can have a debilitating impact on the patients affected,”
said Salim Mujais, M.D., senior vice president and global
therapeutic area head, Medical Specialties Development, Astellas.
“The presented data from two Phase 3 studies conducted in Japanese
patients, showing roxadustat to be well tolerated and efficacious,
support the potential of roxadustat as a new oral therapeutic
option for CKD patients with anemia, including those on HD and on
PD. We look forward to continuing to advance the development of
roxadustat and contributing to a treatment of anemia associated
with CKD.”
The following are highlights of key data from
these two Phase 3 studies of roxadustat:
1517-CL-0302 study
Title: Phase 3, Multicenter, Open-Label
Study of Intermittent Oral Roxadustat in Peritoneal Dialysis CKD
Patients with Anemia
(Publication #: SA-OR075, Oral abstract session on Saturday,
October 27 from 5:54 p.m. to 6:06 p.m. PT at San Diego Convention
Center, Room 2)
Study design
- This multicenter 24-week, randomized, open-label Phase 3 study
enrolled Japanese CKD patients on PD with anemia in two groups
based on prior ESA treatment.
- Patients not previously treated with ESA (ESA Naive) were
randomized to roxadustat 50 mg or 70 mg; patients previously
treated with ESA (ESA Conversion) were switched to roxadustat 70 mg
or 100 mg depending on prior ESA dose.
- Dose was adjusted throughout the study to maintain the Hb
levels at a target range of 10-12 g/dL.
- Efficacy endpoints were maintenance rate of target Hb level at
Weeks 18-24, cumulative response rate at the end of treatment (two
Hb thresholds, 10.0 g/dL and 10.5 g/dL; and Hb increase, ≥1.0
g/dL), average Hb levels at Weeks 18-24 and its change from
baseline, and rate of rise in Hb levels from Week 0 to Week 4.
- Safety was assessed by occurrence of Adverse Events (AEs).
Study results
- 56 patients were enrolled (13 ESA Naive; 43 ESA
Conversion).
- Efficacy endpoints:- Hb maintenance rates were 92.3% (95% CI:
64.0, 99.8; ESA Naive) and 74.4% (95% CI: 58.8, 86.5; ESA
Conversion).- Maintenance rates of patients with at least one Hb
value at Weeks 18-24 were 92.3% (95% CI: 64.0, 99.8; ESA Naive) and
86.5% (95% CI: 71.2, 95.5; ESA Conversion).- In the ESA Naive
Group, cumulative response rate for both Hb thresholds was 100.0%.-
Mean of average Hb levels at Weeks 18-24 were 11.05 g/dL (95% CI:
10.67, 11.42; ESA Naive) and 10.93 g/dL (95% CI: 10.73, 11.13; ESA
Conversion).- Mean change in average Hb at Weeks 18-24 from
baseline was 1.69 g/dL (95% CI: 1.06, 2.33; ESA Naive) and 0.14
g/dL (95% CI: -0.12, 0.39; ESA Conversion).- In the ESA Naive
Group, mean (SD) rate of rise in Hb levels from Week 0 to Week 4
was 0.193 (0.203) and 0.556 (0.408) g/dL/week with roxadustat 50 mg
and 70 mg, respectively.
- The most common treatment emergent adverse events (TEAEs) were
nasopharyngitis, back pain, catheter site infection, diarrhea,
vomiting, abdominal pain, conjunctivitis, constipation, nausea, and
pruritus.
1517-CL-0307 study
Title: Phase 3, Randomized,
Double-Blind, Active-Comparator (Darbepoetin Alfa) Conversion Study
of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in
Japan
(Publication #: TH-PO1151, Poster session on Thursday, October
25 from 10:00 a.m. to 12:00 noon PT at Exhibit hall)
Study design
- This multicenter, 24-week, randomized, double-blind,
double-dummy, darbepoetin-controlled Phase 3 study enrolled
Japanese CKD patients on HD for ≥12 weeks, with anemia converted
from rHuEPO or darbepoetin alpha to roxadustat.
- Patients were randomized to roxadustat (70 mg and 100 mg) three
times weekly or darbepoetin alfa (10-60 μg) once weekly; roxadustat
dose was adjusted to maintain Hb between 10 and12 g/dL.
- Primary endpoint was the change of average Hb levels from
baseline to Weeks 18-24. Roxadustat efficacy was confirmed if the
95% CI of average Hb at Weeks 18-24 was within the range of 10-12
g/dL. Non-inferiority to darbepoetin alfa was confirmed if the
lower limit of the 95% CI of the difference in the means of change
of average Hb levels from baseline to Weeks 18-24 between
roxadustat and darbepoetin alfa was above -0.75 g/dL.
- Secondary endpoints included: average Hb levels of Weeks 18-24,
proportion of patients who achieved an average Hb level of 10-12
g/dL at Weeks 18-24 (maintenance rate), and iron parameters (i.e.,
serum iron, ferritin, Transferrin Saturation (TSAT), transferrin,
and Total Iron Binding Capacity (TIBC)).
- Safety was assessed as occurrence of AEs and ophthalmological
examination (color fundus photography and optical coherence
tomography (OCT)).
Study results
- 303 patients were randomized to roxadustat (n=151) or
darbepoetin alfa (n=152).
- The mean average Hb at Weeks 18-24 was 10.99 g/dL (95% CI:
10.88, 11.10) with roxadustat, confirming its efficacy.
- The difference between roxadustat and darbepoetin alfa in
change of average Hb levels from baseline to Weeks 18-24 was -0.02
g/dL (95% CI: -0.18, 0.15), confirming non-inferiority of
roxadustat efficacy to darbepoetin alfa.
- Hb maintenance rates were 79.3% (95% CI: 72.0, 85.5;
roxadustat) and 83.4% (95% CI: 76.5, 89.0; darbepoetin alfa).
- The proportion of patients with at least one Hb value
maintained at Hb 10-12 g/dL at Weeks 18-24 were 95.2% (95% CI:
89.8, 98.2; roxadustat) and 91.3% (95% CI: 85.3, 95.4; darbepoetin
alfa).
- Among patients taking roxadustat, serum iron, ferritin, and
TSAT were clinically stable; and transferrin and TIBC increased
through Week 4 and then remained stable. No remarkable changes in
iron parameters occurred with darbepoetin alfa.
- The most common TEAEs in both groups were nasopharyngitis,
shunt stenosis, diarrhea, contusion, and vomiting.
- In ophthalmology evaluations, blinded review of color fundus
photography images revealed new or worsening retinal hemorrhage
occurred in 32.4% of patients receiving roxadustat and 36.6% of
patients receiving darbepoetin alfa during treatment; no clinically
meaningful changes in retinal thickness evaluated with OCT were
observed from Week 0 through end of treatment in either of the
treatment groups.
- No increased risk of ophthalmological abnormalities including
retinal hemorrhages were observed in patients treated with
roxadustat compared to darbepoetin alfa.
- Roxadustat was well tolerated with a safety profile similar to
that of darbepoetin alfa and consistent with previous reports.
For more information about roxadustat studies, please visit to
clinicaltrials.gov
at: https://clinicaltrials.gov/ct2/results?term=roxadustat&Search=Search.
About Chronic Kidney Disease (CKD) and
Anemia CKD is estimated to affect more than 200 million
people worldwide*1 and specifically in Japan, the prevalence of CKD
has increased significantly over time.*2 Although CKD can occur at
any age, it becomes more common in aging populations, and the
prevalence is increasing. Anemia is a common complication of CKD
and is associated with significant morbidity and mortality in
dialysis and non-dialysis populations. In addition, CKD can be both
a cause and a consequence of cardiovascular disease and is now a
critical worldwide healthcare issue that represents a large and
growing unmet medical need.____________________________________
1 Ojo, A. Addressing the Global Burden of Chronic Kidney Disease
Through Clinical and Translational Research. Transactions of the
American Clinical and Climatological Association. 2014, No. 125, p.
229-246.2 Nagata M, Ninomiya T, Doi Y, Yonemoto K, Kubo M, Hata J,
Tsuruya K, Iida M, Kiyohara Y. Nephrol Dial Transplant. 2010, Aug,
vol. 25, no.8, 2557-2564.
About Roxadustat Roxadustat, discovered and
developed by FibroGen, is a compound currently in Phase 3
development on a global basis as a potential therapy for anemia
associated with CKD in both patients on dialysis and not on
dialysis. Roxadustat is an orally administered small molecule
inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase
activity. HIF is a protein transcription factor that induces the
natural physiological response to conditions of low oxygen,
"turning on" erythropoiesis (the process by which red blood cells
are produced).
Astellas and FibroGen are collaborating on the development of
roxadustat for the potential treatment of anemia in patients with
CKD and myelodysplastic syndromes in territories including Japan,
Europe, the Commonwealth of Independent States, the Middle East,
and South Africa. FibroGen and AstraZeneca are collaborating on the
development and commercialization of roxadustat for the potential
treatment of anemia in patients with CKD in the U.S., China, and
other markets.
Roxadustat is currently in Phase 3 clinical development for the
treatment of anemia associated with myelodysplastic syndromes (MDS)
in the U.S. and in Phase 2/3 development for MDS in China.
For information about roxadustat studies, please visit
clinicaltrials.gov at this link:
https://clinicaltrials.gov/ct2/results?term=roxadustat&Search=Search.
About AstellasAstellas Pharma
Inc., based in Tokyo, Japan, is a company dedicated to improving
the health of people around the world through the provision of
innovative and reliable pharmaceutical products. For more
information, please visit our website at
https://www.astellas.com/en
About FibroGen FibroGen, Inc., headquartered in
San Francisco, with subsidiary offices in Beijing and Shanghai, is
a leading biopharmaceutical company discovering and developing a
pipeline of first-in-class therapeutics. The company applies
its pioneering expertise in hypoxia-inducible factor (HIF),
connective tissue growth factor (CTGF) biology, and clinical
development to advance innovative medicines for the treatment of
anemia, fibrotic disease, and cancer. Roxadustat, the company’s
most advanced product candidate, is an oral small molecule
inhibitor of HIF prolyl hydroxylase activity, completing worldwide
Phase 3 clinical development for the treatment of anemia in chronic
kidney disease (CKD), with a New Drug Application (NDA) currently
under review by the State Drug Administration (SDA). Roxadustat is
in Phase 3 clinical development in the U.S. and Europe and in Phase
2/3 development in China for anemia associated with myelodysplastic
syndromes (MDS). Pamrevlumab, an anti-CTGF human monoclonal
antibody, is advancing towards Phase 3 clinical development for the
treatment of idiopathic pulmonary fibrosis (IPF) and pancreatic
cancer, and is currently in a Phase 2 trial for Duchenne
muscular dystrophy (DMD). FibroGen is also developing a
biosynthetic cornea in China. For more information, please visit
www.fibrogen.com.
Astellas Cautionary
NotesIn this press release, statements made with respect
to current plans, estimates, strategies and beliefs and other
statements that are not historical facts are forward-looking
statements about the future performance of Astellas. These
statements are based on management’s current assumptions and
beliefs in light of the information currently available to it and
involve known and unknown risks and uncertainties. A number of
factors could cause actual results to differ materially from those
discussed in the forward-looking statements. Such factors include,
but are not limited to: (i) changes in general economic conditions
and in laws and regulations, relating to pharmaceutical markets,
(ii) currency exchange rate fluctuations, (iii) delays in new
product launches, (iv) the inability of Astellas to market existing
and new products effectively, (v) the inability of Astellas to
continue to effectively research and develop products accepted by
customers in highly competitive markets, and (vi) infringements of
Astellas’ intellectual property rights by third parties.
Information about pharmaceutical products
(including products currently in development) which is included in
this press release is not intended to constitute an advertisement
or medical advice.
FibroGen Forward-looking
Statements This release contains forward-looking
statements regarding FibroGen’s strategy, future plans, and
prospects, including statements regarding the development of the
company’s product candidates pamrevlumab and roxadustat, the
potential safety and efficacy profile of our product candidates,
and our clinical, regulatory, and commercial plans, and those of
our partners. These forward-looking statements include, but are not
limited to, statements about our plans, objectives, representations
and contentions and are not historical facts and typically are
identified by use of terms such as “may,” “will”, “should,” “on
track,” “could,” “expect,” “plan,” “anticipate,” “believe,”
“estimate,” “predict,” “potential,” “continue” and similar words,
although some forward-looking statements are expressed differently.
Our actual results may differ materially from those indicated in
these forward-looking statements due to risks and uncertainties
related to the continued progress and timing of our various
programs, including the enrollment and results from ongoing and
potential future clinical trials, and other matters that are
described in our Annual Report on Form 10-K for the fiscal year
ended December 31, 2017, and our Quarterly Report on Form 10-Q for
the fiscal quarter ended June 30, 2018, filed with the Securities
and Exchange Commission (SEC), including the risk factors set forth
therein. Investors are cautioned not to place undue reliance on
these forward-looking statements, which speak only as of the date
of this release, and we undertake no obligation to update any
forward-looking statement in this press release, except as required
by law.
_______________________________________________________________________
Contacts for inquiries or additional
information:Astellas Pharma Inc. Corporate Communications
TEL: +81-3-3244-3201 FAX: +81-3-5201-7473
FibroGen, Inc. Karen L. Bergman Vice President, Investor
Relations and Corporate Communications 1 (415) 978-1433
kbergman@fibrogen.com
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