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LYON, France--(BUSINESS WIRE)--ENYO Pharma (“ENYO”), 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. “The Alpestria-1 results represent a pivotal moment for ENYO and are more importantly a watershed moment for patients living with Alport syndrome” added Jacky Vonderscher, PhD, CEO of ENYO Pharma. 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–angiotensin 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 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, 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 m² 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 “Results 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,” said Prof. Bertrand Knebelmann, MD, PhD, Principal Investigator of the ALPESTRIA-1 study and Chair of the Strategic Advisory Board having reviewed the results. “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 and beyond,” commented Pietro Scalfaro, MD, CMO of ENYO Pharma. “The Alpestria-1 results represent a pivotal moment for ENYO and are more importantly a watershed moment for patients living with Alport syndrome,” added Jacky Vonderscher, PhD, CEO of ENYO Pharma. 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 ENYO 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 : ENYO 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. ENYO Pharma management will be in San Francisco during the upcoming 44th Annual J.P. Morgan Healthcare Conference to discuss these data and the company’s 2026–2031 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 ENYO Pharma SA: ENYO 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 ENYO 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: ENYO Pharma – Developing therapeutics for diseases with impaired kidney function

After attempts to earn a full approval for Ocaliva in primary biliary cholangitis, Intercept Pharmaceuticals is pulling the plug on the drug in the U.S. based on the request of the FDA. After years of regulatory struggles for Intercept Pharmaceuticals and its liver disease drug Ocaliva (obeticholic acid), the FDA has called time on the drug's run in the U.S. market. The agency placed Intercept's trials of obeticholic acid on a clinical hold and requested that the company voluntarily withdraw the drug from the market, where it has been cleared to treat certain patients with primary biliary cholangitis (PBC) since winning an accelerated approval in 2016. Despite Intercept's arduous efforts to obtain full approval for the drug, the company has obliged and will pull the med, it announced in a Sept. 11 press release. “While our view of Ocaliva’s benefit-risk profile differs from FDA’s, we respect its request and have made this difficult decision to provide clear guidance for patients and prescribers,” Intercept’s U.S. president Vivek Devaraj said in a statement. “We remain committed to innovation in hepatology and to serving the needs of patients and physicians.”The development marks the latest setback for Intercept's U.S. market prospects and comes after the FDA’s Gastrointestinal Drug Advisory Committee overwhelmingly voted against Intercept's data package at a meeting last year.Committee members weren’t swayed by Intercept’s clinical trials, nor was the FDA in its pre-meeting briefing documents. In its assessment, the FDA flagged the potential for the drug to put patients at greater risk of needing a liver transplant or death.Soon after the meeting, the FDA rejected Intercept’s bid for a traditional approval. But the agency did allow the drug to remain available for certain patients under its initial accelerated nod while it weighed safety data from a post-marketing study. Still, the company didn’t give up and pledged to generate additional data in support of its drug.But the hits kept on coming. Over in Europe, regulators ultimately snatched back Ocaliva’s marketing nod late last year after a holding period. The repeated setbacks in PBC weren't exactly unfamiliar territory for Intercept. The company had at one point hoped to market the drug as the first treatment for nonalcoholic steatohepatitis, which is now known as metabolic dysfunction-associated steatohepatitis (MASH).That situation saw a similar storyline play out, with two of the company's attempts to win the FDA’s favor falling short. Afterward, Intercept was forced to pivot from its MASH efforts to PBC, trimming a third of its workforce and winding down all MASH-related investments. It was after the MASH rejection that Intercept sold itself to Italian drugmaker Alfasigma in a deal worth about $800 million. At the time in 2023, the company was boasting $285.7 million in full-year 2022 sales for Ocaliva, its lone product.Intercept’s pipeline is made up largely of obeticholic acid, but it lists one other next-generation FXR agonist being tested in a phase 2a study for severe alcohol-associated hepatitis.