ECEESPE2025 Poster Presentations Multisystem Endocrine Disorders (43 abstracts)
-Week Results from the HELIOS Trial: A Phase 2, Open-Label Study Evaluating an Oral, Fixed-Dose Combination of Sodium Phenylbutyrate and Taurursodiol in Wolfram Syndrome
Fumihiko Urano 1 , Bess Marshall 1 , Stacy Hurst 1 , Amy Viehoever 1 , Saumel Ahmadi 1 , Tamara Hershey 1 , Gregory Van Stavern 1 , Paulina Cruz Bravo 1 , Jennifer Powers Carson 1 , Nathalie Erpelding 2 , Kelly Fox 2 , John Pesko 2 & Lahar Mehta 2
1Washington University School of Medicine, St. Louis, USA; 2Amylyx Pharmaceuticals, Inc., Cambridge, USA
JOINT84048
Background: Wolfram syndrome (WS) is a rare, fatal, monogenic disorder characterized by juvenile-onset diabetes mellitus, optic nerve atrophy, sensorineural deafness, diabetes insipidus, and neurodegeneration. Symptoms progress from childhood to adulthood. WS is thought to represent a prototypical syndrome of endoplasmic reticulum (ER) stress with impaired mitochondrial dynamics also contributing to its pathophysiology. PB&TURSO is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO) hypothesized to simultaneously mitigate ER stress and mitochondrial dysfunction. PB&TURSO has demonstrated pre-clinical efficacy in patient-derived cell and mouse WS models. The phase 2, open-label HELIOS trial is evaluating the safety/tolerability of PB&TURSO as well as its effects on endocrinological, neurological, and ophthalmological function in WS.
Methods: Adults (≧ 17 years) with a definite genetic WS diagnosis; insulin-requiring diabetes mellitus due to WS; and stimulated C-peptide levels ≧0.2 ng/mL were enrolled from one U.S. site. Participants receive PB&TURSO for up to 144 weeks. The primary efficacy endpoint is change from baseline in C-peptide at Week 24 using 240-minute mixed meal tolerance tests. Secondary efficacy endpoints include measures of glucose control and best-corrected visual acuity. Exploratory endpoints include clinician- and participant-reported global impression of change scores and participant experiences derived from on-study qualitative interviews.
Results and conclusions: HELIOS week 24 results for all 12 participants (Intent-to-Treat) and for the 11 with genetically confirmed WS (Per Protocol) were previously reported. PB&TURSO was generally well-tolerated with diarrhea the most common adverse event. Due to the progressive nature of WS, pancreatic beta cell function, glycemic control, visual function, and overall symptom burden typically worsen over time; however, at Week 24, treatment with PB&TURSO showed overall stabilization or improvement relative to baseline. Stimulated C-peptide responses showed improvements with a mean change from baseline to Week 24 in C-peptide area under the curve (AUC) from 0 to 120 minutes of +3.8 minutes*ng/mL [standard error (S.E.):19.3] in Intent-to-Treat (n=12) and +20.2 min*ng/mL [S.E.:11.2] in Per Protocol (n=11). Participants also demonstrated improved glycemic control and a trend toward visual acuity stabilization. All participants reported either improvement or stabilization of disease, as measured by Clinician- and Patient-Reported Global Impression of Change scales. Nine of 11 interviewed participants reported improvements in ≧1 WS-related symptom with nearly all noting these were meaningful changes. Available Week 48 results (n=6) suggest sustained stabilization and/or improvement of pancreatic function, glycemic control, vision, and symptom burden. Treatment with PB&TURSO in HELIOS is ongoing. Updated Week 48 results will be presented.
Volume 110
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2025 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more