Ligand Partner Retrophin Reports Additional Positive Data from Phase 2 DUET Study of Sparsentan in Focal Segmental Glomerulosclerosis at ASN Kidney Week 2016
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--(BUSINESS WIRE)--
Ligand Pharmaceuticals Incorporated (NASDAQ:LGND) partner
Retrophin, Inc. 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. Retrophin 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 Ligand Pharmaceuticals
Ligand is a biopharmaceutical company focused on developing or acquiring
technologies that help pharmaceutical companies discover and develop
medicines. Our business model creates value for stockholders by
providing a diversified portfolio of biotech and pharmaceutical product
revenue streams that are supported by an efficient and low corporate
cost structure. Our goal is to offer investors an opportunity to
participate in the promise of the biotech industry in a profitable,
diversified and lower-risk business than a typical biotech company. Our
business model is based on doing what we do best: drug discovery,
early-stage drug development, product reformulation and partnering. We
partner with other pharmaceutical companies to leverage what they do
best (late-stage development, regulatory management and
commercialization) to ultimately generate our revenue. Ligand’s Captisol®
platform technology is a patent-protected, chemically modified
cyclodextrin with a structure designed to optimize the solubility and
stability of drugs. OmniAb® is a patent-protected transgenic
animal platform used in the discovery of fully human mono-and bispecific
therapeutic antibodies. Ligand has established multiple alliances,
licenses and other business relationships with the world's leading
pharmaceutical companies including Novartis, Amgen, Merck, Pfizer,
Celgene, Gilead, Janssen, Baxter International and Eli Lilly.
Follow Ligand on Twitter @Ligand_LGND.
Forward-Looking Statements
This news release contains forward-looking statements by Ligand that
involve risks and uncertainties and reflect Ligand's judgment as of the
date of this release. These include statements regarding the possible
use of sparsentan as a treatment options for FSGS, the timing and
results of review by the Food and Drug Administration (FDA) of
sparsentan, Retrophin’s plans to present the DUET study results at an
upcoming medical meeting or in a peer-reviewed publication, and the
ability of patients to continue in an open-label study of sparsentan.
Actual events or results may differ from our expectations. For example,
Ligand has no control whether Retrophin terminates the open-label study
of sparsentan, including due to adverse events reported by patients,
there can be no assurance that success in a Phase 2 clinical trial will
result in success in future clinical trials; the safety and tolerability
data from a new clinical trial in sparsentan may conflict with the
results of the Phase 2 DUET clinical trial; and the number of patients
diagnoses with FSGS may be more or fewer than Retrophin believes. The
failure to meet expectations with respect to any of the foregoing
matters may reduce Ligand's stock price. Additional information
concerning these and other important risk factors affecting Ligand can
be found in Ligand's prior press releases available at www.ligand.com
as well as in Ligand's public periodic filings with the Securities and
Exchange Commission, available at www.sec.gov.
Ligand disclaims any intent or obligation to update these
forward-looking statements beyond the date of this press release, except
as required by law. This caution is made under the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
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Ligand Pharmaceuticals Incorporated
Todd Pettingill, 858-550-7500
investors@ligand.com
Twitter:
@Ligand_LGND
or
LHA
Bruce Voss, 310-691-7100
bvoss@lhai.com
Source: Ligand Pharmaceuticals Incorporated
Released November 21, 2016