Progressive loss of kidney function is a
validated independent predictor of death and hospitalization in PAH
patients
Reata Pharmaceuticals, Inc. (Nasdaq:RETA) (Reata or Company), a
clinical-stage biopharmaceutical company, today announced results
from the long-term follow up portion of the LARIAT study
demonstrating that pulmonary arterial hypertension (PAH) patients
treated with bardoxolone methyl (bardoxolone) experienced kidney
function improvements that were durable for two years and not
associated with adverse outcomes. The two-year duration of
sustained eGFR improvement in LARIAT is twice as long as Reata has
previously reported for bardoxolone and supports the rationale for
Reata’s ongoing CARDINAL and PHOENIX programs in rare forms of
chronic kidney disease (CKD).
Progressive loss of kidney function is a
prevalent and critical complication for patients with PAH and is a
validated, independent predictor of mortality and all-cause
hospitalization in this population. PAH patients experience
an annualized loss of kidney function of approximately 8 to 13
mL/min/1.73 m2. Patients in the placebo-controlled,
double-blind phase of LARIAT had impaired kidney function upon
study entry with an eGFR averaging 75.6 mL/min/1.73 m2.
Patients who received treatment with bardoxolone (n=71) had
significantly increased eGFR compared to placebo (n=30) by 10.6
mL/min/1.73 m2 (p<0.0001) after 16 weeks of treatment.
After patients in LARIAT completed 16 weeks of
treatment, all patients were eligible to receive bardoxolone in an
open-label extension study. At the time of the analysis, 55
patients had received at least 56 weeks of bardoxolone treatment,
and 26 of these patients had received bardoxolone treatment for at
least 104 weeks. After 56 weeks of treatment, patients
experienced a significant, mean increase in eGFR of 10.7
mL/min/1.73 m2 from baseline (p<0.0001), and after 104 weeks of
treatment, patients experienced a significant, mean increase in
eGFR of 11.3 mL/min/1.73 m2 from baseline (p<0.0001).
Notably, 88% of patients on bardoxolone maintained increases in
eGFR above baseline after two years of treatment. The large
proportion of responders and overall magnitude of improvement that
is durable for two years contrasts with the chronic loss of kidney
function in this patient population.
The LARIAT PAH patients experienced a lower rate
of hospitalization when compared to recent registrational and
observational PAH studies, and there were no deaths among these
LARIAT PAH patients. Upon study entry, the LARIAT PAH
patients had a median time since diagnosis of 3.3 years (n=101; 66
weeks median duration of treatment). For patients with PAH,
the median survival from time of diagnosis is 4 to 7 years.
“Loss of kidney function is common in PAH
patients and associated with an increased risk of adverse outcomes
and death. Treatments for PAH improve symptoms but often
worsen kidney function, placing patients at greater risk,” said
Daniel W. Coyne, M.D., Nephrologist and Professor of Medicine at
Washington University in St. Louis, Missouri. “The two-year
trial data are the longest available with bardoxolone and suggest
raising kidney function with bardoxolone is not harmful and is
likely to be beneficial in PAH patients and other disease
states.”
The two-year eGFR data from LARIAT extend
earlier observations that bardoxolone treatment is associated with
preservation of kidney function. Recently published data from
Reata’s diabetic CKD trials (BEAM and BEACON) demonstrated that
eGFR improvements from bardoxolone treatment were durable for at
least one year and associated with a more than 50% reduced
likelihood of adverse renal events validated to predict kidney
failure. Most important, these data demonstrated that
patients treated with bardoxolone for at least one year had a
persisting improvement in kidney function versus placebo even after
the drug was withdrawn for one month. This persisting
increase after withdrawal suggests that the drug is improving, not
harming, the structure of the kidney in humans as it does in
multiple animal models of CKD.
“Through these analyses of long-term clinical
data, we have been able to differentiate the improvements in kidney
function with bardoxolone from agents that may modestly,
transiently, and adversely increase kidney function by increasing
blood pressure in the kidney,” said Colin Meyer, M.D., Reata’s
Chief Medical Officer. “The longer term data in PAH patients,
who are extremely sensitive to any adverse perturbations of renal
or cardiac function, provides further evidence that bardoxolone may
be beneficial, and not harmful, to the kidney.”
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CONFERENCE CALL INFORMATION |
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Date: |
Tuesday, February 13, 2018 |
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About Kidney Function and
PAH
The role of kidney dysfunction and outcomes in
PAH has recently been characterized in an analysis of data from the
REVEAL registry, the largest US cohort of patients with PAH
(Chakinala et al., 2017). The analysis showed that, in PAH
patients, a decline in renal function was associated with a nearly
two-fold increase in mortality (HR=1.90; p<0.001).
Furthermore, a 10% decrease in eGFR was an independent predictor of
mortality for patients with PAH (HR=1.66; p<0.0001) and also
associated with increased risk for the composite of mortality and
all-cause hospitalization (HR=1.33; p=0.0019). Notably, the
relationship between declining eGFR and survival persisted even
when adjusting for key factors like baseline eGFR, REVEAL risk
score, 6MWD change, and WHO functional class changes.
About LARIAT
LARIAT is a two-part study of the efficacy and
safety of bardoxolone in patients with pulmonary
hypertension. Part 1 was a double-blind, randomized,
placebo-controlled treatment period, and Part 2 was an open-label
extension period. The study enrolled primarily WHO Group I
PAH patients classified as WHO/NYHA Functional Class II and III,
including those with CTD-PAH. Patients receiving one or two
disease-specific PAH therapies, including endothelin receptor
antagonists, riociguat, phosphodiesterase5 (PDE5) inhibitors, or
prostacyclins (subcutaneous, oral, or inhaled), were eligible for
enrollment. Patients from Part 1 who completed the 16-week
treatment period as planned were eligible to continue directly into
the extension period (Part 2) to evaluate the intermediate and
long-term safety and efficacy of bardoxolone.
About Bardoxolone Methyl
Bardoxolone 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. Bardoxolone is currently being
studied in the Phase 3 portion of the CARDINAL trial in patients
with CKD caused by Alport syndrome as well as the Phase 2 PHOENIX
trial in patients with autosomal dominant polycystic kidney
disease, IgA nephropathy, type 1 diabetic CKD, and focal segmental
glomerulosclerosis. In addition to the CARDINAL and PHOENIX
trials, bardoxolone is currently being studied in CATALYST, a Phase
3 study for the treatment of connective tissue disease associated
pulmonary arterial hypertension. The FDA has granted orphan
designation to bardoxolone for the treatment of Alport syndrome and
the treatment of pulmonary arterial hypertension.
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.
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, 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,” 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) 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 (iv) 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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