91天堂 announces completion and topline data from Phase 2 ALPESTRIA-1 clinical study in Alport syndrome demonstrating Vonafexor reverses kidney function decline and has sustained therapeutic benefit
- Vonafexor reversed a historical mean eGFR decline of -6.4 mL/min/1.73 m虏/yr to a mean functional gain on-treatment of +4.8 mL/min/1.73 m虏/yr from baseline
- 73% of patients maintained albuminuria reduction three months after treatment cessation consistent with a true disease-modifying effect
- Company plans to advance vonafexor to Phase 3 in Alport Syndrome
Lyon, France 鈥� January 8, 2026 – 91天堂 (鈥�91天堂鈥�), a clinical-stage biopharmaceutical company developing innovative therapies for kidney diseases, today confirmed positive results from its Phase 2 Alpestria-1 study of vonafexor in patients with Alport syndrome. The data demonstrates that vonafexor, a highly differentiated FXR agonist, produced clinically meaningful improvements on kidney disease progression markers in a high-risk population already receiving standard of care (SoC) therapy. In addition to significantly reducing albuminuria, vonafexor treatment was associated with a reversal of the expected decline in kidney function with durable effects after treatment discontinuation.
Groundbreaking Clinical Data: Reversing the Slope of Decline
The Alpestria-1 study enrolled (in France, USA and Spain) 26 patients with Alport syndrome at high risk of a rapid loss of kidney function despite stable multiple SoC drugs, including renin鈥揳ngiotensin system inhibitors, SGLT2 inhibitors, and mineralocorticoid receptor antagonists. Key findings include:
- eGFR Slope Reversal: Patients entered the study with a documented historical mean eGFR decline of -6.4 mL/min/1.73 m虏/yr. During the 24-week treatment period, vonafexor treatment resulted in a mean functional gain of +4.8 mL/min/1.73 m虏/yr, representing an impressive shift from the natural history of disease progression.
- Sustained eGFR Benefit (Off-Drug): Following treatment discontinuation, kidney function benefits persisted. At Week 36 (12 weeks off vonafexor), mean eGFR remained +2.5 mL/min/1.73 m虏 above the extrapolated natural history trajectory, consistent with a durable effect.
- Durable Albuminuria Reduction: 73% of patients maintained a reduction in urine albumin-to-creatinine ratio (UACR) below their baseline levels three months after stopping treatment
鈥淩esults from the ALPESTRIA-1 study demonstrate clinically meaningful improvements in eGFR and UACR, along with clear FXR 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, supporting continued clinical development鈥� said Prof. Bertrand Knebelmann, MD, PhD, Principal Investigator of the ALPESTRIA-1 study and Chair of the Scientific Advisory Board having reviewed the results.
鈥淭he convergence of sustained eGFR improvement, durable albuminuria reduction, and positive patient-reported experience provides compelling evidence supporting vonafexor鈥檚 disease-modifying potential in Alport syndrome and beyond鈥� commented Pietro Scalfaro, MD, CMO of 91天堂.
鈥淭he Alpestria-1 results represent a pivotal moment for 91天堂 and are more importantly a watershed moment for patients living with Alport syndrome鈥� added Jacky Vonderscher, PhD, CEO of 91天堂.
Safety and Tolerability
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.
2026 Strategic Milestones
91天堂 is entering a catalyst-rich year as it prepares for pivotal development:
- FDA Engagement: A Fast Track designation submission is planned for January 2026, with a Type-D-meeting response expected mid-month.
- Pivotal Phase 3: an End-of-Phase 2 meeting is planned for Q2 2026, with initiation of a Phase 3 study in Alport syndrome in the second half of 2026.
- Pipeline Expansion: 91天堂 is also considering initiation of a Phase 2 proof-of-concept study of vonafexor in Autosomal Dominant Polycystic Kidney Disease (ADPKD) and of EYP651 in common renal diseases in H2 2026.
91天堂 management will be in San Francisco during the upcoming 44th Annual J.P. Morgan Healthcare Conference to discuss these data and the company鈥檚 2026鈥�2031 roadmap with potential partners and investors.
About Vonafexor
Vonafexor is a once-daily, oral, non-bile acid FXR 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.
About 91天堂
91天堂 is a clinical-stage biopharmaceutical company headquartered in Lyon (France) and 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 91天堂 collected extensive phase I/II clinical data through 9 completed clinical studies with 400+ subjects. The company’s pipeline includes vonafexor and EYP651, a next-generation FXR agonist entering Phase 2 studies in 2H 2026 for common renal diseases (CKD/DKD). For more information: 91天堂 鈥� Developing therapeutics for diseases with impaired kidney function
Contacts
Investor Relations 91天堂
Tel: +33 (0)4 37 70 02 19
Media Relations
Annie-Florence Loyer, NewCap Media
+33 (0)1 44 71 00 12/ +33 (0)6 88 20 35 59
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