Significant reduction of proteinuria compared to irbesartan
Statistically significant difference in modified partial remission; complete remission also observed
Further analysis supports sparsentan generally safe and well-tolerated
SAN DIEGO, Nov. 19, 2016 (GLOBE NEWSWIRE) -- Retrophin, Inc. (NASDAQ:RTRX) today announced additional results
from the Phase 2 DUET study of sparsentan for the treatment of focal segmental glomerulosclerosis (FSGS), a rare kidney disorder
without an FDA-approved pharmacologic treatment that often leads to end-stage renal disease. These new findings are being presented
today in the late-breaking High-Impact Clinical Trials oral session at the American Society of Nephrology (ASN) Kidney Week 2016 in
Chicago.
“The prevalence of FSGS is on the rise and without an approved therapy, many patients diagnosed with the
disorder face a progressive decline and the high likelihood of end-stage renal disease,” said Howard Trachtman, MD, Professor of
Pediatrics; Director, Division of Pediatric Nephrology, NYU School of Medicine, NYU Langone Medical Center. “These findings from
the DUET study underscore the potential of sparsentan as a first-in-class treatment for FSGS.”
As announced in September, top-line data from DUET showed the sparsentan treatment group achieved
statistical significance in the study’s primary efficacy endpoint, reduction of proteinuria. These results showed a greater than
two-fold reduction of proteinuria compared to irbesartan, after an eight-week, double-blind treatment period.
An analysis of the secondary endpoint presented today showed that a significantly greater proportion of patients
receiving sparsentan achieved modified partial remission of proteinuria, compared to irbesartan-treated patients. Modified partial
remission, defined as proteinuria levels of less than or equal to 1.5 g/g and greater than 40 percent reduction of proteinuria from
baseline, is associated with long-term preservation of renal function in FSGS. In addition, four patients receiving sparsentan
achieved complete remission, compared to zero irbesartan-treated patients. Also presented today was a post-hoc, intention-to-treat
(ITT) analysis showing that the sparsentan treatment group again demonstrated a greater than two-fold reduction of proteinuria,
compared to irbesartan. Further analysis of the safety database from the initial eight-week, double-blind treatment period
presented today showed sparsentan was generally safe and well-tolerated.
“These new results add to the growing body of evidence from the DUET study, reinforcing our confidence that
sparsentan may represent a significant advancement in the treatment of FSGS,” said Stephen Aselage, chief executive officer of
Retrophin. “We thank the DUET investigators for their diligence, as well as the patients and their families for their commitment to
finding new and better treatment options for FSGS.”
New findings from the DUET study presented at ASN Kidney Week include:
- An analysis of the secondary endpoint, which showed that after the eight-week, double-blind treatment period, 28.1 percent of
patients receiving sparsentan (n=64) achieved modified partial remission of proteinuria, compared to 9.4 percent of
irbesartan-treated patients (n=32, p=0.040).
- The proportion of patients achieving modified partial remission increased during the open label period. After 48 weeks of
treatment with sparsentan (n=26), 57.7 percent of patients achieved modified partial remission. In addition, 50.0 percent of
patients that transferred from irbesartan to sparsentan at the beginning of the open label period achieved modified partial
remission after 40 weeks of treatment (n=12).
- Complete remission, defined as proteinuria less than 0.3 g/g, was achieved by four patients receiving sparsentan during the
eight-week, double-blind treatment period, compared to zero irbesartan-treated patients.
- A post-hoc ITT analysis (imputing zero change in proteinuria for the 13 patients missing baseline or week 8 data) showed a
statistically significant difference in the mean reduction of proteinuria from baseline for the sparsentan treatment group
(n=73), compared to the irbesartan group (n=36), after the study’s eight-week, double-blind treatment period. The sparsentan
group achieved a 42.7 percent mean reduction of proteinuria compared to 15.7 percent for the irbesartan group (p=0.004).
- The ITT analysis also showed that after eight weeks of treatment with 400 mg and 800 mg of sparsentan (n=60), the mean
reduction of proteinuria from baseline was 44.8 percent, compared to 15.9 percent for the irbesartan-treated patients in these
two cohorts (n=28, p=0.008).
- During the eight-week, double-blind period, the incidence of treatment-emergent adverse events (TEAE) for the sparsentan
group was similar to the irbesartan group, except for edema. The severity of edema did not significantly worsen from baseline and
no patients withdrew from the study as a result of edema during the eight-week, double-blind treatment period. The most common
TEAEs in the study were headache, hypotension, dizziness, edema, nausea, diarrhea, vomiting and upper abdominal pain. The
incidence of serious adverse events was similar across both groups.
- 84 percent of patients who completed the eight-week, double-blind treatment period continue to receive sparsentan in the
open-label extension.
About the DUET Study
The DUET study is an international, randomized, double-blind, Phase 2 clinical trial assessing the safety and
efficacy of sparsentan in 109 patients with primary focal segmental glomerulosclerosis (FSGS), of which 96 qualified for the
evaluable efficacy database. The primary endpoint is the reduction of proteinuria, as compared to irbesartan, which is part of a
class of drugs used to manage FSGS in the absence of an FDA-approved pharmacologic treatment. After a two-week washout period,
patients were randomized to receive daily oral doses of 200 mg, 400 mg, and 800 mg of sparsentan or 300 mg of irbesartan. After
completing an initial eight weeks of randomized treatment, all patients were eligible to receive sparsentan as part of the study’s
open-label extension.
About Focal Segmental Glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis, or FSGS, is a rare disorder without an FDA-approved pharmacologic treatment
option that is estimated to affect up to 40,000 patients in the U.S. with similar prevalence in Europe. The disorder
is defined by progressive scarring of the kidney and often leads to end-stage renal disease. FSGS is characterized by proteinuria,
where protein is found in the urine due to a breakdown of the normal filtration mechanism in the kidney. Other common symptoms
include swelling in parts of the body known as edema, as well as low blood albumin levels, abnormal lipid profiles, and
hypertension.
Reduction in proteinuria is widely regarded to be beneficial in the treatment of FSGS, and may be associated
with a decreased risk of progression to end-stage renal disease. Achieving modified partial remission of proteinuria, defined as
proteinuria levels of less than or equal to 1.5 g/g and greater than 40 percent reduction of proteinuria from baseline, is
associated with long-term preservation of renal function in patients with FSGS. In the absence of an FDA-approved pharmacologic
treatment, patients with FSGS are currently managed with angiotensin receptor blockers, angiotensin converting enzyme inhibitors,
calcineurin inhibitors, and steroids.
About Sparsentan
Sparsentan could be the first FDA-approved pharmacologic treatment for focal segmental glomerulosclerosis, or
FSGS, a rare kidney disorder that often leads to end-stage renal disease. Sparsentan’s dual mechanism of action combines
angiotensin receptor blockade with endothelin receptor type A blockade. In several forms of chronic kidney disease, endothelin
receptor blockade has been shown to have an additive beneficial effect on proteinuria in combination with renin-angiotensin
blockade via angiotensin receptor blockade or angiotensin converting enzyme inhibitors.
The Phase 2 DUET study of sparsentan met the primary efficacy endpoint for the combined treatment group,
demonstrating a greater than two-fold reduction of proteinuria compared to irbesartan, after the eight-week, double-blind treatment
period. The Company is working with the FDA to determine the most expeditious path forward to advance the development of
sparsentan towards approval. In 2015, the FDA and European Commission each granted sparsentan orphan drug
designation for the treatment of FSGS.
About Retrophin
Retrophin is a fully integrated biopharmaceutical company dedicated to delivering life-changing therapies to
people living with rare diseases who have few, if any, treatment options. The Company’s approach centers on its pipeline featuring
clinical-stage assets targeting rare diseases with significant unmet medical needs, including sparsentan for focal segmental
glomerulosclerosis (FSGS), a disorder characterized by progressive scarring of the kidney often leading to end-stage renal disease,
and RE-024 for pantothenate kinase-associated neurodegeneration (PKAN), a life-threatening neurological disorder that typically
begins in early childhood. Research exploring the potential of early-stage assets in several rare diseases is also underway.
Retrophin’s R&D efforts are supported by revenues from the Company’s commercial products Thiola®, Cholbam®, and Chenodal®.
Retrophin.com
Forward-Looking Statements
This press release contains “forward-looking statements” as that term is defined in the Private Securities
Litigation Reform Act of 1995. In addition, expressions of our strategies, intentions or plans are also forward-looking statements.
Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors
that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current
expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ
materially from those indicated in the forward-looking statements are risks and uncertainties associated with the Company’s
business and finances in general, as well as risks and uncertainties associated with the Company’s research, preclinical, and
clinical-stage pipeline. Specifically, the Company faces the risk that additional clinical trials will be required for regulatory
approvals, risk that additional clinical trials, if any, will fail to demonstrate that sparsentan is safe or effective, and risk
that the sparsentan program will be delayed for regulatory or other reasons. You are cautioned not to place undue reliance on these
forward-looking statements as there are important factors that could cause actual results to differ materially from those in
forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update
forward-looking statements, whether as a result of new information, future events, or otherwise. Investors are referred to the full
discussion of risks and uncertainties as included in the Company’s filings with the Securities and Exchange
Commission.
Contacts: (Investors) Chris Cline, CFA Senior Director, Investor Relations 646-564-3680 IR@retrophin.com (Media) Scott Santiamo Associate Director Corporate Communications 718-344-5843 scott.santiamo@retrophin.com
