Mezzion Reports Positive In Vivo Results for PDE5 Inhibitor Udenafil in ADPKD, Plans Phase 2b Trial
核心洞察
Udenafil, a novel PDE5 inhibitor, demonstrated statistically significant reductions in kidney cyst burden and blood urea nitrogen in a preclinical ADPKD model at Mayo Clinic.
The study also showed evidence of cGMP pathway activity in the kidney and a significant reduction in a preclinical measure of cardiac hypertrophy.
Mezzion plans to advance udenafil into a Phase 2b study in adults at risk of rapidly progressing ADPKD, pending regulatory and ethics approvals.
Mezzion Pharma (搜索) Co., Ltd. today announced positive results from a new in vivo study of udenafil, a novel phosphodiesterase type 5 (搜索) (PDE5) inhibitor, in autosomal dominant polycystic kidney disease (搜索) (ADPKD). The preclinical study, conducted at Mayo Clinic in Florida with Fouad T. Chebib, M.D. serving as principal investigator, demonstrated that udenafil reduced kidney cyst burden and blood urea nitrogen (BUN), a blood marker linked to kidney function, compared with controls. Both findings were statistically significant and consistent across the treatment groups evaluated.
The results build on two earlier preclinical studies in which udenafil inhibited cyst growth and reduced cyst burden. Across these complementary ADPKD models, udenafil has shown activity on its intended cGMP pathway, reduced measures of cystic disease, and improved a biochemical measure used in kidney assessment.
Evidence of cGMP Pathway Activity and Cardiac Benefit
The study also showed evidence of activity on udenafil's intended cyclic guanosine monophosphate (cGMP) signaling pathway in the kidney. In addition, udenafil produced a statistically significant reduction in a preclinical measure of cardiac hypertrophy, or heart enlargement. Because cardiovascular complications are an important part of ADPKD, this finding supports further study of udenafil's potential effects on cardiac remodeling.
"These findings strengthen the scientific rationale for advancing udenafil in ADPKD," said Dong Hyun Park, Chairman and CEO of Mezzion. "As previously announced, the U.S. Food and Drug Administration (FDA) indicated that Mezzion's nonclinical data package, together with its prior clinical and safety experience with udenafil, provides a reasonable foundation for clinical development."
A Mechanistically Distinct Approach
Unlike vasopressin V2 receptor antagonists, udenafil is being investigated through modulation of the nitric oxide-cGMP pathway, providing a mechanistically distinct therapeutic approach. Professor Yong Chul Kim of Seoul National University Hospital noted, "The preclinical data provide a compelling scientific rationale for clinical evaluation in ADPKD. Unlike vasopressin V2 receptor antagonists, udenafil is being investigated through modulation of the nitric oxide-cGMP pathway, providing a mechanistically distinct therapeutic approach."
Ronald D. Perrone, M.D., of Tufts Medicine, added, "The consistency across multiple preclinical models is encouraging and supports evaluating udenafil in a well-designed Phase 2b study using established measures of ADPKD progression."
Clinical Development History and Next Steps
Udenafil has been studied in multiple clinical programs over approximately 20 years, including studies with multi-year exposure. This experience will help inform ADPKD study design and safety monitoring, according to the company.
Mezzion plans to advance udenafil into a Phase 2b study in adults at risk of rapidly progressing ADPKD, subject to finalization of the protocol and receipt of regulatory and ethics approvals. The planned study is expected to evaluate kidney volume and function, disease-related biomarkers, pharmacokinetics, safety, and tolerability.
"Patients with ADPKD need more treatment options for this serious, lifelong disease," said Ridwan Shabsigh, M.D., FACS, President and COO of Mezzion. "Advancing udenafil in ADPKD gives Mezzion a second rare-disease development program alongside our ongoing Phase 3 FUEL-2 study."
Disease Background
ADPKD is a progressive genetic kidney disease affecting approximately 1 in 400 to 1,000 people worldwide. As kidney cysts grow, kidney function can decline and ultimately lead to dialysis or kidney transplantation. ADPKD is also associated with cardiovascular and other complications.
Mezzion Pharma (搜索) Co., Ltd., based in Korea and listed on the KOSDAQ, is a clinical-stage biopharmaceutical company focused on developing therapies for rare and underserved diseases. Udenafil is an investigational product and has not been approved by any regulatory authority.