Ligand Partner Retrophin Announces Positive Top-Line Results from Phase 2 DUET Study of Sparsentan in Patients with Focal Segmental Glomerulosclerosis
Combined sparsentan treatment group experienced 44.8% reduction of
proteinuria, more than double the reduction of irbesartan; achieves
statistical significance in primary efficacy endpoint
Preliminary safety findings show sparsentan was generally safe and
well-tolerated
SAN DIEGO--
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) partner Retrophin,
Inc. (NASDAQ: RTRX) today announced positive top-line results from the
Phase 2 DUET study of sparsentan for the treatment of focal segmental
glomerulosclerosis (FSGS), a rare kidney disorder without an approved
pharmacologic treatment that often leads to end-stage renal disease. The
study achieved statistical significance in the primary efficacy endpoint
for the overall sparsentan treatment group, demonstrating a greater than
two-fold reduction of proteinuria compared to irbesartan after the
eight-week, double-blind treatment period.
“Retrophin has reported notable top-line results from the Sparsentan
DUET trial, and we commend their team for the successful outcome of this
study,” said John Higgins, CEO of Ligand Pharmaceuticals. “We are proud
of our partnership with Retrophin and the early collaborative work we
did to help support this program. Sparsentan is one of Ligand’s top
partnered portfolio assets, and we are very pleased to see this asset
progress.”
“We are very pleased with the robust top-line results from DUET, which
suggest sparsentan could be a significant advancement in the treatment
of FSGS,” said Stephen Aselage, CEO of Retrophin. “FSGS patients today
face poor outcomes with limited medical options; we look forward to
working with the FDA to find the most expeditious path forward that
would deliver the first approved pharmacologic treatment to the FSGS
community.”
In the DUET study, according to Retrophin’s announcement, the mean
reduction of proteinuria from baseline after eight weeks of treatment
for all patients treated with 200, 400, and 800 mg/day of sparsentan
(n=64) was 44.8%, compared to a mean reduction of proteinuria for all
patients receiving 300 mg/day of irbesartan (n=32) of 18.5% (p=0.006).
Further, the mean reduction of proteinuria from baseline after eight
weeks of treatment for all patients treated with 400 mg and 800 mg doses
of sparsentan (n=51) was 47.4%, compared to a mean proteinuria reduction
of 19.0% for patients receiving 300 mg of irbesartan (n=25) in these two
dose cohorts (p=0.011). The comparison of individual sparsentan dose
cohorts to irbesartan showed clear signals of relative improvement, but
did not reach statistical significance.
“The results from DUET serve as proof of concept for sparsentan’s novel
approach of combining endothelin receptor type A blockade with
angiotensin II inhibition for the treatment of FSGS,” said Alvin Shih,
M.D., executive vice president and head of research & development for
Retrophin. “Significant reductions in proteinuria, along with a
well-tolerated preliminary safety profile have us excited about being
one step closer to providing a new treatment option for patients with
FSGS.”
According to Retrophin’s announcement, top-line results suggest
sparsentan was generally safe and well-tolerated in the DUET study. One
serious adverse event, anemia, classified as potentially related to
treatment occurred in the sparsentan group but did not result in study
discontinuation during the eight-week blinded treatment period. There
were no withdrawals due to fluid retention during the eight-week blinded
treatment period. All patients who completed the eight-week treatment
period entered the ongoing open label extension study, and the vast
majority of these patients continue to receive therapy.
Retrophin announced that it plans to present detailed study results,
including data from the open label extension, at an upcoming medical
meeting or in a peer-reviewed publication.
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 focal segmental glomerulosclerosis (FSGS), of which 96
qualified for the evaluable database. The primary endpoint was 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 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 the eight-week
treatment period, 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 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. In the absence of an approved
pharmacologic treatment, FSGS patients are currently managed with
angiotensin receptor blockers, angiotensin converting enzyme inhibitors,
calcineurin inhibitors, and steroids.
About Sparsentan
Sparsentan could be the first 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.
According to Retrophin’s announcement, the Phase 2 DUET study of
sparsentan met the primary efficacy endpoint for the overall treatment
group, demonstrating a greater than two-fold reduction of proteinuria
compared to irbesartan, after the eight-week, double-blind treatment
period. Retrophin announced that it plans to engage the FDA to determine
the most expeditious path forward to advance the development of
sparsentan towards approval. In 2015, the U.S. Food and Drug
Administration 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. Retrophin'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 Retrophin's commercial products
Thiola®, Cholbam® and Chenodal®.
Retrophin.com
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,
Retrophin may choose to terminate 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20160907005974/en/
Ligand Pharmaceuticals Incorporated
Todd Pettingill, 858-550-7500
investors@ligand.com
or
LHA
Bruce
Voss, 310-691-7100
bvoss@lhai.com
Source: Ligand Pharmaceuticals Incorporated
Released September 7, 2016