ENYO Pharma's Vonafexor Reverses Kidney Function Decline in Phase 2 Alport Syndrome Trial
核心洞察
ENYO Pharma's Phase 2 Alpestria-1 study demonstrated that vonafexor reversed historical kidney function decline from -6.4 mL/min/1.73 m²/yr to a mean functional gain of +4.8 mL/min/1.73 m²/yr in Alport syndrome (搜索) patients.
The FXR (搜索) agonist showed durable effects with 73% of patients maintaining albuminuria reduction three months after treatment cessation, suggesting disease-modifying potential.
The company plans to advance vonafexor to Phase 3 development in Alport syndrome (搜索), with FDA Fast Track designation submission planned for January 2026.
ENYO Pharma announced positive topline results from its Phase 2 Alpestria-1 study of vonafexor in patients with Alport syndrome (搜索), demonstrating the drug's ability to reverse kidney function decline and produce sustained therapeutic benefits. The clinical-stage biopharmaceutical company reported that vonafexor, a highly differentiated FXR (搜索) agonist, achieved clinically meaningful improvements in kidney disease progression markers in high-risk patients already receiving standard of care therapy.
Reversing Disease Progression
The Alpestria-1 study enrolled 26 patients with Alport syndrome (搜索) across France, USA, and Spain who were at high risk of rapid kidney function loss despite receiving stable multiple standard of care drugs, including renin-angiotensin system inhibitors, SGLT2 inhibitors, and mineralocorticoid receptor antagonists.
The most striking finding was the reversal of estimated glomerular filtration rate (eGFR) decline. Patients entered the study with a documented historical mean eGFR decline of -6.4 mL/min/1.73 m²/yr. During the 24-week treatment period, vonafexor treatment resulted in a mean functional gain of +4.8 mL/min/1.73 m²/yr from baseline, representing what the company described as "an impressive shift from the natural history of disease progression."
Sustained Benefits After Treatment
The therapeutic effects persisted beyond the treatment period. Following treatment discontinuation, kidney function benefits continued, with mean eGFR remaining +2.5 mL/min/1.73 m² above the extrapolated natural history trajectory at Week 36 (12 weeks off vonafexor). This durability suggests a potential disease-modifying effect rather than merely symptomatic treatment.
Additionally, 73% of patients maintained a reduction in urine albumin-to-creatinine ratio (UACR) below their baseline levels three months after stopping treatment, further supporting the drug's disease-modifying potential.
Clinical Expert Perspectives
Prof. Bertrand Knebelmann, MD, PhD, Principal Investigator of the ALPESTRIA-1 study and Chair of the Strategic Advisory Board, stated: "Results from the ALPESTRIA-1 study demonstrate clinically meaningful improvements in eGFR and UACR, along with clear FXR (搜索) target engagement at low doses. These findings confirm a differentiated mechanism of action consistent with preclinical data and position vonafexor as a promising therapeutic candidate for Alport syndrome (搜索), supporting continued clinical development."
Pietro Scalfaro, MD, CMO of ENYO Pharma, commented: "The convergence of sustained eGFR improvement, durable albuminuria reduction, and positive patient-reported experience provides compelling evidence supporting vonafexor's disease-modifying potential in Alport syndrome (搜索) and beyond."
Safety Profile
Vonafexor was generally well-tolerated, with a safety profile consistent with previous clinical trials involving over 400 subjects. The most common adverse event was pruritus, which was dose dependent and manageable through dose adjustments while maintaining pharmacological activity and efficacy.
Development Timeline and Strategic Milestones
ENYO is preparing for pivotal development with several key milestones planned for 2026. The company plans to submit for FDA Fast Track designation in January 2026, with a Type-D-meeting response expected mid-month. An End-of-Phase 2 meeting is scheduled for Q2 2026, with initiation of a Phase 3 study in Alport syndrome (搜索) planned for the second half of 2026.
The company is also considering pipeline expansion, including initiation of a Phase 2 proof-of-concept study of vonafexor in Autosomal Dominant Polycystic Kidney Disease (搜索) (ADPKD) and of EYP651 in common renal diseases in H2 2026.
Drug Mechanism and Company Background
Vonafexor is a once-daily, oral, non-bile acid FXR (搜索) agonist designed with a unique chemical scaffold that prioritizes delivery to the kidney. By regulating metabolic, inflammatory, and fibrotic pathways, vonafexor addresses the core drivers of renal injury and extracellular matrix remodeling.
ENYO Pharma is a clinical-stage biopharmaceutical company headquartered in Lyon, France, developing proprietary drug candidates to improve quality of life and avoid end-stage renal disease and dialysis for patients with rare and common kidney diseases. Since its inception, ENYO has collected extensive phase I/II clinical data through 9 completed clinical studies with over 400 subjects.
Jacky Vonderscher, PhD, CEO of ENYO Pharma, emphasized the significance of the results: "The Alpestria-1 results represent a pivotal moment for ENYO and are more importantly a watershed moment for patients living with Alport syndrome (搜索)."