Amylyx Publishes Phase 2 HELIOS Trial Results Showing Continued Benefits of AMX0035 in Wolfram Syndrome
Amylyx Pharmaceuticals announced that detailed Week 24 and Week 48 findings from the Phase 2 HELIOS clinical trial evaluating AMX0035 in adults living with Wolfram syndrome have been published in The Journal of Clinical Investigation. The publication provides expanded peer-reviewed data demonstrating continued improvements in pancreatic beta cell function, stabilization of visual outcomes, and favorable safety observations in patients affected by the rare genetic disorder.
The HELIOS study evaluated AMX0035, an oral fixed-dose combination therapy composed of sodium phenylbutyrate and taurursodiol. The investigational treatment is being explored as a potential disease-modifying therapy for Wolfram syndrome, a progressive and life-threatening neurodegenerative disease for which no approved disease-modifying treatments currently exist.
According to Amylyx, the newly published data build upon findings previously presented at scientific and medical conferences, further supporting the therapeutic potential of AMX0035 across both the endocrine and neurological manifestations of the disease.
Wolfram syndrome is a rare inherited disorder that typically begins during childhood and is commonly characterized by insulin-dependent diabetes mellitus and progressive vision loss caused by optic nerve degeneration. As the disease advances, patients may also develop hearing impairment, neurological decline, bladder dysfunction, balance problems, and other complications that can significantly impair quality of life and reduce life expectancy.
Because the disorder affects multiple organ systems and progressively worsens over time, treatment options remain extremely limited. Current medical management is largely focused on symptom control and supportive care rather than slowing or altering disease progression.
The HELIOS trial findings suggest that AMX0035 may offer potential benefits in addressing some of the core biological mechanisms involved in Wolfram syndrome. According to the publication, improvements in pancreatic beta cell function were observed through Week 48, as measured by C-peptide response during a mixed-meal tolerance test.
C-peptide is considered an important marker of endogenous insulin production and pancreatic beta cell activity. Preserving or improving beta cell function is particularly significant in Wolfram syndrome because patients often experience severe insulin deficiency due to progressive pancreatic dysfunction.
In addition to improvements in beta cell function, secondary measures of glycemic control also demonstrated favorable trends during the study period. Researchers reported improvements from baseline in hemoglobin A1c levels, commonly known as HbA1c, as well as increased time spent within the target glucose range of 70 to 180 mg/dL at both Week 24 and Week 48.
These findings suggest that AMX0035 may contribute to improved glucose regulation and metabolic stability in patients living with Wolfram syndrome, potentially reducing some of the disease burden associated with diabetes management.
The publication also highlighted ophthalmologic findings from the study. Best-corrected visual acuity, a key measure of visual function, showed trends toward stabilization over the 48-week evaluation period. Given the progressive nature of optic nerve degeneration in Wolfram syndrome, stabilization of vision may represent an important clinical outcome for affected patients.
Researchers further noted that participant and clinician assessments using Global Impression of Change measures classified participants with available data as responders. In the context of the trial, responders were defined as individuals demonstrating either measurable improvement or stabilization of disease progression.
Fumihiko Urano, who also serves as the Samuel E. Schechter Professor of Medicine in the Division of Endocrinology, Metabolism & Lipid Research at Washington University School of Medicine in St. Louis, emphasized the serious nature of Wolfram syndrome and the lack of available disease-modifying therapies.
According to Urano, the disease presents substantial challenges for both patients and families because it typically begins early in life with insulin-requiring diabetes and progressive visual impairment before expanding into broader neurological complications that increasingly interfere with daily functioning.
Urano stated that, within this context, the publication of the Week 24 and Week 48 HELIOS results is particularly encouraging. He noted that the observed improvements in pancreatic function combined with stabilization of visual acuity and a favorable safety profile reinforce the possibility that AMX0035 could meaningfully alter the disease trajectory for patients living with Wolfram syndrome.
Amylyx executives also highlighted the importance of the published data, particularly given the advanced disease status of patients enrolled in the study.
Camille L. Bedrosian explained that the peer-reviewed publication provides a detailed overview of AMX0035’s clinical effects across both endocrine and neurodegenerative aspects of the disease. Bedrosian noted that the results are especially notable because all participants enrolled in the trial were at least 17 years old and had already experienced considerable disease progression by the time they entered the study.
According to Bedrosian, the company remains grateful to the patients, families, investigators, and clinical site personnel who contributed to the trial and helped advance research in this underserved disease area. She also stated that Amylyx continues to work with the U.S. Food and Drug Administration regarding plans for a future Phase 3 clinical trial in Wolfram syndrome.
In addition to quantitative clinical endpoints, the publication included findings from qualitative participant interviews conducted during the study. These interviews provided insight into how patients perceived the impact of treatment on their daily lives.
According to the publication, participants described meaningful improvements related to diabetes management and visual function, supporting the clinical relevance of the objective measures reported during the trial. Such patient-reported experiences may provide additional context regarding how therapeutic changes translate into practical benefits for individuals living with the disease.
Safety findings reported in the publication remained consistent with previous clinical experience involving AMX0035. Investigators stated that reported adverse events were generally mild or moderate in severity, and no serious adverse events related to treatment were identified during the study period.
The HELIOS study is a single-site, single-arm, open-label Phase 2 clinical trial evaluating AMX0035 in 12 adult participants with Wolfram syndrome. Patients enrolled in the study may receive treatment for up to 208 weeks, followed by an additional four-week safety follow-up period.
Although the study involves a relatively small patient population due to the rarity of the disease, researchers believe the data provide important insights into the potential role of AMX0035 in slowing or stabilizing disease progression.
Amylyx stated that additional longer-term findings from the HELIOS trial are expected to be presented at an upcoming scientific meeting. The company believes continued follow-up may further clarify the durability of observed treatment effects and help guide future development plans.
AMX0035 has previously attracted attention in the neurodegenerative disease field due to its proposed mechanism targeting cellular stress pathways associated with mitochondrial dysfunction and endoplasmic reticulum stress. These biological processes are believed to contribute to cell death and progressive tissue damage in multiple neurodegenerative conditions, including Wolfram syndrome.
The therapy combines sodium phenylbutyrate and taurursodiol, two compounds intended to work together to protect cellular health and improve survival of vulnerable cells under stress conditions. Researchers believe this mechanism may help preserve pancreatic beta cells, neurons, and other tissues affected by degenerative disease processes.
The publication of the HELIOS findings represents another important milestone for Amylyx as the company continues expanding research into rare neurological and metabolic disorders with significant unmet medical need.
Looking ahead, the company plans to continue discussions with regulators regarding the design and advancement of a Phase 3 program while also generating additional long-term data from the ongoing HELIOS study. If future studies confirm the benefits observed thus far, AMX0035 could potentially emerge as one of the first disease-modifying therapeutic options for individuals living with Wolfram syndrome.
About AMX0035
AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the U.S.). AMX0035 was designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration.
Amylyx believes that its proprietary combination of PB and TURSO and their complementary mechanisms of action will allow us to synergistically target abnormal cell death to better prevent neurodegeneration than treatment targeted at either mechanism of action alone. The FDA and the European Commission granted Orphan Drug Designation to AMX0035 for the treatment of Wolfram syndrome in November 2020 and August 2024, respectively.
About Wolfram Syndrome
Wolfram syndrome is a rare, monogenic, progressive neurodegenerative disorder that progressively impacts multiple organs and systems. Wolfram syndrome is characterized by childhood-onset diabetes mellitus, optic nerve atrophy, and neurodegeneration. Common manifestations of Wolfram syndrome include diabetes mellitus and diabetes insipidus, gradual vision loss leading to blindness, hearing loss, neurogenic bladder, difficulties with balance and coordination, and difficulty breathing that can lead to respiratory failure and premature mortality.
Wolfram syndrome is most commonly caused by pathogenic variants in Wolfram syndrome type 1 gene (WFS1). Because of the clear link between WFS1 mutations and endoplasmic reticulum (ER) stress, Wolfram syndrome is considered a prototypical ER stress disorder. Wolfram syndrome affects approximately 3,000 people living in the U.S., and there are currently no FDA-approved treatment options.
About the HELIOS Trial
HELIOS (NCT05676034) is a 12-participant, single-site, single-arm, open-label, Phase 2 trial designed to evaluate the safety and tolerability of AMX0035, as well as its effects on various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome. Participants in HELIOS receive AMX0035 for up to 208 weeks followed by a four-week safety follow-up. Primary and secondary outcomes are assessed at Week 24 and at longer-term time points.
About Amylyx Pharmaceuticals
At Amylyx, our mission is to usher in a new era of treating diseases with high unmet needs. Where others see challenges, we see opportunities that we pursue with urgency, rigorous science, and unwavering commitment to the communities we serve. We are currently focused on four investigational therapies across several endocrine conditions and neurodegenerative diseases in which we believe can make the greatest impact.
