Reata Pharmaceuticals, Inc. (Nasdaq:RETA) (“Reata” or the
“Company”), a clinical-stage biopharmaceutical company, announced
today that the Phase 3 portion of the CARDINAL study of bardoxolone
methyl (bardoxolone) in patients with chronic kidney disease (CKD)
caused by Alport syndrome met its primary and key secondary
endpoints. After 48 weeks of treatment, patients treated with
bardoxolone had a statistically significant improvement compared to
placebo in mean estimated glomerular filtration rate (eGFR) of 9.50
mL/min/1.73 m2 (p<0.0001). After 48 weeks of treatment and
a four-week withdrawal period, patients treated with bardoxolone
had a statistically significant improvement compared to placebo in
mean retained eGFR of 5.14 mL/min/1.73 m2 (p=0.0012).
Bardoxolone treatment was generally reported to be
well-tolerated and showed a similar safety profile to the Phase 2
portion of the CARDINAL study. Based on these positive
results, and subject to discussions with regulatory authorities,
the Company plans to proceed with the submission of regulatory
filings for marketing approval in the United States and
internationally.
“The first year results from the CARDINAL study
are very promising. This provides hope to the entire Alport
syndrome community that we could finally have the first therapy to
treat this rare, genetic kidney disease,” said Lisa Bonebrake,
Executive Director of the Alport Syndrome Foundation. “The
Alport Syndrome Foundation is grateful to the patients who
participated in the study. Their willingness to contribute to
our understanding of bardoxolone is a gift to all patients facing
the devastating impact that Alport syndrome can have on their
lives, others with the disease in their family, and those who care
about them. We also extend our deepest gratitude to the
clinicians and their institutions for conducting this study and
caring for these patients through the process, and to Reata
Pharmaceuticals for investing their scientific expertise in the
search to find a therapy for Alport syndrome.”
“Patients living with Alport syndrome experience
a severe and progressive loss of kidney function that can lead to
the need for chronic dialysis treatment or a kidney transplant in
the prime of their lives. The CARDINAL trial of bardoxolone
is the first study in which a therapy halted the progression of
chronic kidney disease in patients with Alport syndrome,” said
Warren Huff, Reata’s President and Chief Executive Officer.
“On behalf of everyone at Reata, I would like to express my
sincere appreciation to all of the patients, families, and
investigators who are participating in the ongoing CARDINAL
study.”
Trial Overview and Results
The Phase 3 portion of CARDINAL is an
international, multi-center, double-blind, placebo-controlled,
randomized registrational trial that enrolled 157 patients with
Alport syndrome at approximately 50 study sites in the United
States, Europe, Japan, and Australia. Pediatric patients
represented approximately 15% of enrolled patients. Patients
were randomized 1:1 to bardoxolone or placebo. The primary
endpoint for the study was the change in eGFR, an important measure
of the ability of the kidney to filter waste products out of the
blood, after 48 weeks of treatment. The key secondary
endpoint for the study was the change in the retained eGFR after 48
weeks of treatment and four weeks of drug withdrawal. After
52 weeks, patients who completed the first 48 weeks of treatment
are restarted on study drug with their original treatment
assignments and continue on study drug for a second year. The
second-year on-treatment eGFR will be measured after 100 weeks of
treatment and the retained eGFR will be measured at Week 104 after
withdrawal of drug for four weeks. The FDA has provided the
Company with written guidance that, in patients with CKD caused by
Alport syndrome, an analysis of retained eGFR demonstrating an
improvement versus placebo after one year of bardoxolone treatment
may support accelerated approval and an improvement versus placebo
after two years of treatment may support full approval.
After 48 weeks of treatment, patients treated
with bardoxolone had a statistically significant improvement
compared to placebo in mean eGFR of 9.50 mL/min/1.73 m2
(p<0.0001). Patients treated with bardoxolone experienced
a statistically significant increase from baseline in mean eGFR of
4.72 mL/min/1.73 m2, while patients treated with placebo
experienced a statistically significant decline from baseline in
mean eGFR of -4.78 mL/min/1.73 m2. Patients’ retained eGFR
was also assessed at Week 52, after 48 weeks of treatment and four
weeks of drug withdrawal. At Week 52, patients treated with
bardoxolone had a statistically significant improvement compared to
placebo in mean retained eGFR of 5.14 mL/min/1.73 m2
(p=0.0012). Patients treated with bardoxolone experienced a
nonsignificant decline from baseline in mean retained eGFR of -0.96
mL/min/1.73 m2, while patients treated with placebo experienced a
statistically significant decline from baseline in mean retained
eGFR of -6.11 mL/min/1.73 m2. Similar efficacy at Week 48 and
Week 52 was observed across multiple subgroups, including among
pediatric patients.
Bardoxolone was generally reported to be well
tolerated in this study and showed a similar safety profile to the
Phase 2 portion of the CARDINAL study. Seventy-five patients
(97%) receiving bardoxolone and 73 patients (91%) receiving placebo
experienced an adverse event (AE). Nine patients (12%)
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.
Four patients (5%) receiving bardoxolone and 10
patients (13%) receiving placebo experienced a treatment-emergent
serious adverse event (SAE). No fluid overload or major
adverse cardiac events were reported in patients treated with
bardoxolone. Blood pressure was reduced relative to baseline
in the bardoxolone group, and the between group difference was not
significant. 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 increases in aminotransferases and muscle
spasms. Increases in aminotransferases are a pharmacological
effect of bardoxolone, which increases production of
aminotransferases in vitro. The aminotransferase increases
observed in CARDINAL were associated with improvements (reductions)
in total bilirubin and were not associated with liver injury, and
we believe they are related to restoration of mitochondrial
function. Laboratory markers associated with pharmacodynamic
activity, including urinary albumin to creatinine ratio and
aminotransferases, were unchanged relative to placebo at Week 52
following withdrawal of drug for four weeks.
Reata management will host a call to discuss
these results as well as the financial results for the third
quarter of 2019 tomorrow, November 12, 2019 at 8:00 a.m. ET.
CONFERENCE CALL INFORMATION
Date: |
November 12, 2019 |
Time: |
8:00 a.m. ET |
Audience Dial-in (toll-free): |
(844) 348-3946 |
Audience Dial-in (international): |
(213) 358-0892 |
Conference ID: |
4159656 |
Webcast Link: |
https://edge.media-server.com/mmc/p/ofwujzj9 |
|
|
About the Retained eGFR
Analysis
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.
The FDA has accepted for approval in rare forms
of CKD the placebo-corrected “retained eGFR” after withdrawal of
drug. Withdrawal of drug after long-term treatment provides
evidence whether a drug either protected or harmed the kidney
during treatment. If retained eGFR is higher than placebo,
this is evidence that the drug protected the kidney during
treatment, and, if retained eGFR is lower than placebo, this is
evidence that the drug harmed the kidney during treatment. A
positive retained eGFR benefit 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. Alport syndrome patients experience a
progressive loss in the kidney’s capacity to filter waste products
out of the blood that can lead to end stage kidney failure (ESKD)
and the need for chronic dialysis treatment or a kidney
transplant. A majority of patients with Alport syndrome
develop ESKD, and approximately 50% of patients with the most
severe form of the disease require dialysis or a kidney transplant
by the age of 25. 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 Alport syndrome.
About Bardoxolone Methyl
Bardoxolone methyl is an experimental, 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.
Bardoxolone is currently being studied in
CARDINAL, a Phase 3 study for the treatment of Alport syndrome,
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 CATALYST, a Phase 3 study for
the treatment of connective tissue disease associated with
pulmonary arterial hypertension. 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 restoration of mitochondrial function,
reduction of oxidative stress, and inhibition of pro-inflammatory
signaling. Bardoxolone and omaveloxolone are
investigational drugs, and their safety and efficacy have not been
established by any agency.
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 its Annual Report on Form 10-K, under the
caption “Risk Factors.” 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.
Contact:Reata Pharmaceuticals, Inc.(972)
865-2219info@reatapharma.comhttp://news.reatapharma.com
Investor Relations:Vinny JindalVice President,
Strategy(469) 374-8721ir@reatapharma.com
Media:Matt Middleman, M.D.LifeSci Public
Relations(646)
627-8384matt.middleman@lifescipublicrelations.com
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