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Concert Pharmaceuticals Presents
Positive 48-Week Results from Phase 2 Clinical Trial of CTP-499 in
Diabetic Kidney Disease
- CTP-499 observed to protect against large increases in serum
creatinine
- CTP-499 reduced biomarkers of fibrosis
- Data presented at late-breaking session at the National Kidney
Foundation Spring Clinical Meeting
LAS VEGAS--April 25, 2014-- Concert Pharmaceuticals, Inc. (NASDAQ: CNCE)
today announced 48-week results of its Phase 2 clinical trial of CTP-499
in patients with diabetic kidney disease. CTP-499, when used in addition
to the standard of care, is being developed to delay the progression of
these patients to end-stage renal failure, which requires dialysis or
kidney transplantation. The results suggest that CTP-499 has protective
effects on kidney function in patients with type 2 diabetic kidney
disease, a condition in which kidney function is progressively lost. In
addition, an observed, statistically significant reduction of certain
fibrotic biomarkers suggests that CTP-499 may act as an anti-fibrotic
agent. The results were presented today during a Late-Breaking session
at the National Kidney Foundation 2014 Spring Clinical Meeting by Dr.
Bhupinder Singh, a clinical investigator and Medical Director of Apex
Research of Riverside.
"The results of this Phase 2 trial after 48 weeks were highly
encouraging and, I believe, support the progression of CTP-499 into
larger clinical trials. Overall, these data suggest that CTP-499 may
protect patients from suffering loss of kidney function by reducing the
progression of fibrosis," said Dr. Singh. "Fibrosis is believed to be a
final common pathway for kidney failure due to diabetic kidney disease,
a gradual process that occurs over the course of years. Importantly, the
biomarker data suggesting predominately anti-fibrotic activity may
explain why CTP-499 treatment required a 48 week treatment period to
demonstrate a clinical effect."
Dr. Singh added, "There is an enormous need for new mechanisms, such as
inhibition of fibrosis, to treat chronic kidney disease. A new treatment
that is well-tolerated and slows the progression of disease could
potentially have a major impact on patients' lives."
The Phase 2 trial was a placebo-controlled, multi-center trial involving
three parts:
• Part 1—a double-blind, randomized, parallel, two-arm,
placebo-controlled study evaluating the safety and efficacy, as measured
by urinary albumin to creatinine ratio (UACR), of 600 mg CTP-499 twice
daily for 24 weeks. 151 of 182 patients enrolled completed Part 1.
• Part 2—an optional blinded extension study in which all patients who
completed Part 1 were eligible to continue receiving 600 mg of CTP-499
or placebo twice daily for an additional 24 weeks. 123 of 143 patients
enrolled completed Part 2.
• Part 3—all patients who completed Part 2 were eligible to continue
with up to 48 weeks of open-label treatment and receive 600 mg of
CTP-499 twice daily. This open-label study is ongoing.
At 48 weeks, a measurable impact on serum creatinine, a key secondary
endpoint, was observed. Increased serum creatinine is a marker of
impaired kidney function. These data may indicate a slower decline of
kidney function in patients treated with CTP-499 compared to those who
received placebo.
• The mean serum creatinine level in the 65 patients receiving CTP-499
increased by 0.13 mg/dL compared to an increase of 0.21 mg/dL in the 58
patients receiving placebo through the 48 weeks of treatment (p =
0.057), reflecting a 38% improvement.
• Six out of the 58 patients receiving placebo, or 10.3%, experienced a
50% or greater increase in serum creatinine levels after 48 weeks
compared with one out of the 65 patients receiving CTP-499, or 1.5% (p =
0.026).
The primary endpoint of the trial was the change after 24 weeks in UACR,
a marker of kidney tissue damage. While the trial did not meet this
endpoint, at 48 weeks the longer-term treatment duration suggests a
favorable trend in UACR for patients receiving CTP-499 as compared to
placebo. At 48 weeks, UACR in patients receiving CTP-499 increased 24
mg/g from baseline compared to 223 mg/g increase in patients receiving
placebo (p = 0.097). These data may indicate a stabilization of UACR in
patients treated with CTP-499 compared to those who received placebo.
The treatment effects observed at 48 weeks were accompanied by
statistically significant changes in urinary fibronectin and plasma
collagen IV, two fibrotic biomarkers evaluated in the Phase 2 trial.
Treatment with CTP-499 resulted in 52% less urinary fibronectin (p =
0.0081) and 18% less plasma collagen IV (p = 0.022) after 48 weeks
compared to placebo. As with other endpoints in the Phase 2 trial, no
significant changes in fibronectin and collagen IV were observed after
24 weeks of treatment, whereas significant effects in these biomarkers
were seen after 48 weeks of treatment.
Treatment with CTP-499 was generally well tolerated. Gastrointestinal
events were reported more frequently in the CTP-499 arm, with mild to
moderate nausea being the most commonly reported event. There were a
total of 33 patients with at least one serious adverse event reported in
the trial; none of these serious adverse events were judged by the
investigators to be possibly related to study drug. These events
occurred in 20% of patients receiving CTP-499 and 17% of patients
receiving placebo. Fewer patients dropped out of the CTP-499 arm than
the placebo arm throughout the course of the trial.
"We are encouraged by our 48-week CTP-499 data and have submitted an end
of Phase 2 meeting request to the FDA to discuss our development pathway
and potential Phase 3 endpoints," said Roger Tung, Ph.D., President and
Chief Executive Officer of Concert Pharmaceuticals. "Diabetic kidney
disease is now the nation's leading cause of dialysis, kidney transplant
and death from kidney failure. We believe that CTP-499 has a novel
mechanism of action for diabetic kidney disease and has the potential to
provide a new treatment option for patients with this debilitating and
life-threatening condition."
About Diabetic Kidney Disease
Diabetic kidney disease, a condition in which kidney function is
progressively lost, can result in the need for dialysis or kidney
transplantation. It is associated with increased morbidity and
mortality, and is the leading cause of end-stage renal disease. The
current standard of care for chronic kidney disease is treatment with
ACEis and/or ARBs, which are blood pressure lowering agents that affect
the renin-angiotensin system. Despite the availability of these
treatments, many patients progress to end stage renal failure and
require dialysis or kidney transplants. Approximately 40% of patients
with a history of type 2 diabetes are believed to have diabetic kidney
disease.
About CTP-499
CTP-499 is a novel, deuterium-containing, oral multi-subtype selective
PDE inhibitor that is being developed to slow the progression of type 2
diabetic kidney disease in patients with macroalbuminuria. In
preclinical testing, CTP-499 suppressed fibrotic, inflammatory and
oxidative processes associated with the pathophysiology of diabetic
kidney disease. CTP-499 is a deuterated analog of
1-(S)-5-hydroxyhexyl-3,7-dimethylxanthine, or HDX, an active metabolite
of pentoxifylline. It is being developed as an additive treatment to
angiotensin modulation with an ACEi or ARB, which is the current
standard of care for type 2 diabetic kidney disease.
About Concert
Concert Pharmaceuticals is a clinical stage biopharmaceutical company
focused on applying its DCE Platform® (deuterated chemical entity
platform) to create novel small molecule drugs. This approach starts
with approved drugs, advanced clinical candidates or previously studied
compounds that have the potential to be improved with deuterium
substitution to enhance clinical safety, tolerability and efficacy. The
company is developing a broad pipeline targeting CNS disorders, renal
disease, inflammation and cancer.
Cautionary Note on Forward Looking Statements
Any statements in this press release about our future expectations,
plans and prospects, including statements about the potential
effectiveness of CTP-499 in treating diabetic kidney disease, our plans
and timelines for pursuing clinical development and regulatory approval
of CTP-499 and other statements containing the words "anticipate,"
"believe," "continue," "could," "estimate," "expect," "intend," "may,"
"plan," "potential," "predict," "project," "should," "target," "would,"
and similar expressions, constitute forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by such
forward-looking statements as a result of various important factors,
including: the uncertainties inherent in the initiation of future
clinical trials, availability and timing of data from ongoing and future
clinical trials and the results of such trials, whether preliminary
results from a clinical trial will be predictive of the final results of
that trial or whether results of early clinical trials will be
indicative of the results of later clinical trials, expectations for
regulatory approvals and other factors discussed in the "Risk Factors"
section of our Annual Report on Form 10-K filed with the Securities and
Exchange Commission on March 31, 2014 and in other filings that we make
with the Securities and Exchange Commission. In addition, any
forward-looking statements included in this press release represent our
views only as of the date of this release and should not be relied upon
as representing our views as of any subsequent date. We specifically
disclaim any obligation to update any forward-looking statements
included in this press release.
Concert Pharmaceuticals Inc., the CoNCERT Pharmaceuticals Inc. logo and
DCE Platform are registered trademarks of Concert Pharmaceuticals, Inc.
Contact
Concert Pharmaceuticals, Inc.
Justine Koenigsberg (investors), 781-674-5284
ir @concertpharma.com
or
The Yates Network
Kathryn Morris (media), 845-635-9828
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