- 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
"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:
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 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
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.
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.
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
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