Reata Pharmaceuticals, Inc. (Nasdaq:RETA) (“Reata” or the
“Company,” or “we”), a clinical-stage biopharmaceutical company,
today announced that the Phase 3 CARDINAL study of bardoxolone
methyl (“bardoxolone”) in patients with chronic kidney disease
(“CKD”) caused by Alport syndrome met its primary and key secondary
endpoints at the end of Year 2. At Week 100, in the intent-to-treat
(“ITT”) population, which included estimated glomerular filtration
rate (“eGFR”) values for patients who either remained on or
discontinued study drug, patients treated with bardoxolone had a
statistically significant improvement compared to placebo in mean
change from baseline in eGFR of 7.7 mL/min/1.73 m2 (p=0.0005). In
the modified ITT (“mITT”) analysis, which assessed the effect of
receiving treatment by excluding values after patients discontinued
treatment, patients treated with bardoxolone had a statistically
significant improvement compared to placebo in mean change from
baseline in eGFR at Week 100 of 11.3 mL/min/1.73 m2 (p<0.0001).
At Week 104 (four weeks after last dose in second year of
treatment), patients in the ITT population treated with bardoxolone
had a statistically significant improvement compared to placebo in
mean change from baseline in eGFR of 4.3 mL/min/1.73 m2 (p=0.023).
Bardoxolone treatment was generally reported to be well-tolerated.
In the long-term extension study (“EAGLE”), for the 14 patients who
completed three years of treatment, bardoxolone treatment resulted
in a mean increase from baseline in eGFR of 11.0 mL/min/1.73
m2. Based on these positive results and following a
recently completed pre-NDA meeting with the U.S. Food and Drug
Administration (“FDA”), we plan to proceed with the submission of
an NDA for full marketing approval in the United States in the
first quarter of 2021. We also plan to pursue marketing
approval outside of the United States and work has commenced on
preparations to file for marketing approval in Europe.
“The positive results of the CARDINAL trial in the
treatment of children and adults with Alport syndrome increase the
potential of this novel therapeutic agent to be approved as the
first specific treatment for this type of chronic kidney disease.
For patients with limited treatment options and faced with a kidney
disorder characterized by relentless progression, the potential
availability of an additional and long-awaited therapy is very
exciting. This is particularly true for children with Alport
syndrome, whose important results in CARDINAL emphasizes the
benefit of early diagnosis and treatment,” said Bradley Warady, MD,
Director, Division of Nephrology/ Dialysis and Transplantation at
Children’s Mercy Kansas City.
“It’s an exciting time for the nephrology
community. As potentially the first specific therapy for Alport
syndrome, bardoxolone could bring hope to thousands of Alport
syndrome patients, their caregivers and families. In addition, its
novel mechanism of action suggests that it could prove effective
against other kidney diseases whose unmet clinical need is just as
great,” said Kerry Willis, Ph.D., Chief Scientific Officer of the
National Kidney Foundation.
“Chronic kidney disease caused by Alport syndrome
is a serious, progressive disease with an urgent need for new
therapeutic options. The two-year CARDINAL study, now
complete, represents the first time that an investigational
medicine has shown a significant clinical benefit in this disease,
and it marks an important step toward making a treatment available
for patients with Alport syndrome. We look forward to submitting
our New Drug Application for bardoxolone in the first quarter of
2021. On behalf of everyone at Reata, I would like to express my
sincere appreciation to all of the patients, families, and
investigators who participated in the CARDINAL study,” said Warren
Huff, Reata’s President and Chief Executive Officer.
CARDINAL Trial Overview
and Results
The Phase 3 CARDINAL study was an international,
multi-center, double-blind, placebo-controlled, randomized clinical
trial that enrolled 157 patients with Alport syndrome at
approximately 50 study sites in the United States, Europe, Japan,
and Australia. Patients were randomized 1:1 to bardoxolone or
placebo. The primary endpoint for Year 2 of the study was the
change from baseline in eGFR after 100 weeks of treatment
(end-of-treatment). The key secondary endpoint for Year 2 of the
study was the change from baseline in eGFR at Week 104 (four weeks
after last dose in second year of treatment).
At Week 100, in the ITT population, patients
treated with bardoxolone had a statistically significant
improvement compared to placebo in mean change from baseline in
eGFR of 7.7 mL/min/1.73 m2 (p=0.0005). Patients treated with
bardoxolone experienced a mean change from baseline in eGFR of -0.8
mL/min/1.73 m2, while patients treated with placebo experienced a
mean change from baseline in eGFR of -8.5 mL/min/1.73
m2. In the mITT analysis, patients treated with
bardoxolone had a statistically significant improvement compared to
placebo in mean change from baseline in eGFR at Week 100 of 11.3
mL/min/1.73 m2 (p<0.0001). Patients treated with bardoxolone
experienced a mean increase from baseline in eGFR of 1.7
mL/min/1.73 m2, while patients treated with placebo experienced a
mean decline from baseline in eGFR of -9.6 mL/min/1.73
m2. At Week 104 (four weeks after last dose in second
year of treatment), patients in the ITT population treated with
bardoxolone had a statistically significant improvement compared to
placebo in mean change from baseline in eGFR of 4.3 mL/min/1.73 m2
(p=0.023). Patients treated with bardoxolone experienced a mean
change from baseline in eGFR of -4.5 mL/min/1.73 m2, while patients
treated with placebo experienced a mean change from baseline in
eGFR of -8.8 mL/min/1.73 m2.
Efficacy was observed across multiple subgroups at
Week 100 and Week 104, including pediatric patients and patients
with different genetic subtypes of Alport syndrome. The largest
treatment effect at Week 104 was observed in the pediatric subgroup
where the difference between treatment groups was 14.6 mL/min/1.73
m2 (p=0.004). The risk of kidney failure events
(defined as end stage kidney disease, confirmed 30% eGFR decline,
or confirmed eGFR < 15 mL/min/1.73 m2) was reduced by
approximately 50% in bardoxolone-treated patients (9 patients
versus 17 patients in placebo).
Bardoxolone was generally reported to be well
tolerated in this study, and the safety profile was similar to that
observed in prior trials. Seventy-five patients (97%) receiving
bardoxolone and 77 patients (96%) receiving placebo experienced an
adverse event (“AE”). Ten patients (13%) receiving bardoxolone and
four patients (5%) receiving placebo discontinued study drug due to
an AE, and no individual AE contributed to more than two
discontinuations in either group. The reported AEs were generally
mild to moderate in intensity, and the most common AEs observed
more frequently in patients treated with bardoxolone compared to
patients treated with placebo were muscle spasms and increases in
aminotransferases.
Eight patients (10%) receiving bardoxolone and 15
patients (19%) receiving placebo experienced a treatment-emergent
serious adverse event (“SAE”). No SAEs were reported in pediatric
patients treated with bardoxolone. No fluid overload or major
adverse cardiac events were reported in patients treated with
bardoxolone. Blood pressure was not significantly different between
the two groups. The urinary albumin-to-creatinine ratio (“UACR”)
was not significantly different between treatment groups at Week
100 or Week 104. Non-kidney symptoms associated with Alport
syndrome, including psychiatric, hearing, vestibular, and ocular
AEs, occurred less frequently in bardoxolone-treated patients.
EAGLE Long Term
Results
Today, we announced results from the long-term
extension study, called EAGLE, that included enrollment of eligible
patients with Alport syndrome who completed the CARDINAL study.
Change from baseline in eGFR was assessed for 14 patients with
Alport syndrome who were treated with bardoxolone for three years,
with four-week off treatment periods occurring at Weeks 48 and 100.
Bardoxolone produced a mean increase from baseline in eGFR of 11.5
mL/min/1.73 m2 at Year 1, 13.3 mL/min/1.73 m2 at Year 2, and 11.0
mL/min/1.73 m2 at Year 3.
Conference Call Information
Reata management will host a call to discuss these
results as well as the financial results for the third quarter of
2020 today, November 9, 2020 at 8:00 a.m. ET. The
conference call will be accessible by dialing (844) 348-3946
(toll-free domestic) or (213) 358-0892 (international) using the
access code: 2896858. The webcast link is
https://edge.media-server.com/mmc/p/z6fgbcwf.
Third quarter 2020 financial results to be
discussed during the call will be available on the Company’s
website shortly before the call at
http://reatapharma.com/investors/ and will be available for 12
months after the call. The audio recording and webcast will be
accessible for at least 90 days after the event at
http://reatapharma.com/investors/.
About the Off-Treatment
eGFR Endpoint
CKD is characterized by a progressive worsening in
the rate at which the kidney filters waste products from the blood
called the glomerular filtration rate or GFR. When GFR falls too
low, patients require dialysis or a kidney transplant to survive.
Dialysis leads to a reduced quality of life and increases the
likelihood of serious and life-threatening complications. The
five-year survival rate for hemodialysis patients is only
approximately 42%. eGFR is an estimate of GFR that nephrologists
use to track the decline in kidney function and progression of
CKD.
In rare forms of CKD, the FDA has accepted the
off-treatment endpoint as the basis for approval. Withdrawal of
drug after long-term treatment provides evidence whether a drug
either protected or harmed the kidney during treatment. If
off-treatment changes in eGFR are higher than placebo, this is
evidence that the drug protected the kidney during treatment, and,
if off-treatment changes in eGFR are lower than placebo, this is
evidence that the drug harmed the kidney during treatment. An
off-treatment eGFR benefit relative to placebo provides evidence
that drug treatment may delay kidney failure.
About Alport Syndrome
Alport syndrome is a rare, genetic form of CKD
caused by mutations in the genes encoding type IV collagen, which
is a major structural component of the glomerular basement membrane
in the kidney. The kidneys of patients with Alport syndrome
progressively lose the capacity to filter waste products out of the
blood, which can lead to end-stage kidney disease and the need for
chronic dialysis treatment or a kidney transplant. Alport syndrome
affects both children and adults. In patients with the most severe
forms of the disease, approximately 50% progress to dialysis by age
25, 90% by age 40, and nearly 100% by age 60. According to the
Alport Syndrome Foundation, Alport syndrome affects approximately
30,000 to 60,000 people in the United States. There are currently
no approved therapies to treat CKD caused by Alport syndrome.
About Bardoxolone Methyl
Bardoxolone methyl is an investigational, oral,
once-daily activator of Nrf2, a transcription factor that induces
molecular pathways that promote the resolution of inflammation by
restoring mitochondrial function, reducing oxidative stress, and
inhibiting pro-inflammatory signaling. The FDA has granted Orphan
Drug designation to bardoxolone for the treatment of Alport
syndrome. The European Commission has granted Orphan Drug
designation in Europe to bardoxolone for the treatment of Alport
syndrome.
In addition to the CARDINAL Phase 3 study,
bardoxolone is currently being studied in FALCON, a Phase 3 study
for the treatment of autosomal dominant polycystic kidney disease,
AYAME, a Phase 3 study for the treatment of diabetic kidney disease
that is being conducted by our licensee, Kyowa Kirin Co., Ltd., in
Japan, and BARCONA, an investigator-sponsored Phase 2 study for the
treatment in patients suffering from COVID-19 conducted by
researchers at NYU Grossman School of Medicine. Bardoxolone
treatment has produced positive results in Phase 2 studies in
patients with IgA nephropathy, focal segmental glomerulosclerosis,
and CKD associated with type 1 diabetes.
About Reata Pharmaceuticals,
Inc.
Reata is a clinical-stage biopharmaceutical company
that develops novel therapeutics for patients with serious or
life-threatening diseases by targeting molecular pathways involved
in the regulation of cellular metabolism and inflammation. Reata’s
two most advanced clinical candidates, bardoxolone and
omaveloxolone, target the important transcription factor Nrf2 that
promotes the resolution of inflammation by restoring mitochondrial
function, reducing oxidative stress, and inhibiting
pro-inflammatory signaling. Bardoxolone is
an investigational drug,
and its safety and
efficacy have not been established by any
regulatory agency.
Contact:Reata Pharmaceuticals,
Inc.(972) 865-2219http://reatapharma.com
Investors Relations &
Media:Vinny Jindal (469) 374-8721Jami Taylor (469)
262-6451ir@reatapharma.commedia@reatapharma.comhttp://reatapharma.com/contact-us/
Forward-Looking Statements
This press release includes certain disclosures
that contain “forward-looking statements,” including, without
limitation, statements regarding the success, cost and timing of
our product development activities and clinical trials, our plans
to research, develop and commercialize our product candidates, our
plans to submit regulatory filings, and our ability to obtain and
retain regulatory approval of our product candidates. You can
identify forward-looking statements because they contain words such
as “believes,” “will,” “may,” “aims,” “plans,” “model,” and
“expects.” Forward-looking statements are based on
Reata’s current expectations and assumptions. Because
forward-looking statements relate to the future, they are subject
to inherent uncertainties, risks, and changes in circumstances that
may differ materially from those contemplated by the
forward-looking statements, which are neither statements of
historical fact nor guarantees or assurances of future performance.
Important factors that could cause actual results to differ
materially from those in the forward-looking statements include,
but are not limited to, (i) the timing, costs, conduct, and outcome
of our clinical trials and future preclinical studies and clinical
trials, including the timing of the initiation and availability of
data from such trials; (ii) the timing and likelihood of regulatory
filings and approvals for our product candidates; (iii) whether
regulatory authorities determine that additional trials or data are
necessary in order to obtain approval; (iv) the potential market
size and the size of the patient populations for our product
candidates, if approved for commercial use, and the market
opportunities for our product candidates; and (v) other factors set
forth in Reata’s filings with the U.S. Securities and Exchange
Commission, including the detailed factors discussed under the
caption “Risk Factors” in its Annual Report on Form 10-K for the
fiscal year ended December 31, 2019. The forward-looking statements
speak only as of the date made and, other than as required by law,
we undertake no obligation to publicly update or revise any
forward-looking statements, whether as a result of new information,
future events, or otherwise.
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