Relyvrio (phenylbutyrate/taurursodiol) / Amylyx, NeoPharm - LARVOL DELTA

METabolic MODulation to Enhance Insulin Sensitivity and Mitochondrial Function in Type 1 Diabetes (MetMod-T1D) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: University of Washington | Initiation date: Jun 2026 ➔ Sep 2026

Trial initiation date • Diabetes • Endocrine Disorders • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

METabolic MODulation to Enhance Insulin Sensitivity and Mitochondrial Function in Type 1 Diabetes (MetMod-T1D) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: University of Washington

New P2 trial • Diabetes • Endocrine Disorders • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Five-Year Survival Of 42% In ALS Patients Treated With Masitinib: Long-Term Outcomes From AB10015 Trial (ENCALS 2026) - "Objectives This post-hoc analysis evaluated long-term survival outcomes (>5 years from symptom onset) in patients treated with oral masitinib as an add-on therapy to riluzole in the phase 2b/3 study, AB10015...AMX0035 currently lacks established long-term survival data for ALS patients beyond 2 years, with 51.6% versus 89.2% for masitinib (4.5 mg/kg/day).Conclusion These findings underscore masitinib's potential to improve outcomes for patients with ALS. The greatest survival benefit is associated with starting treatment early (i.e., prior to severe functional impairment). A recently identified biomarker detecting masitinib's effect on pathological pro-inflammatory microglia may help identify responsive patients."

Clinical

Efficacy of Sodium Phenylbutyrate-Taurursodiol in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. (PubMed, Ann Indian Acad Neurol) - "Based on very low certainty evidence, the available RCT data do not support a definitive conclusion regarding the efficacy of PB-TURSO in ALS. Post hoc exploratory analyses suggest a potential survival benefit, which requires confirmation in adequately powered, prospectively designed trials; current results are hypothesis-generating rather than practice-defining."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Efficacy of Sodium Phenylbutyrate-Taurursodiol in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. (PubMed, Ann Indian Acad Neurol) - "Based on very low certainty evidence, the available RCT data do not support a definitive conclusion regarding the efficacy of PB-TURSO in ALS. Post hoc exploratory analyses suggest a potential survival benefit, which requires confirmation in adequately powered, prospectively designed trials; current results are hypothesis-generating rather than practice-defining."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Amyotrophic Lateral Sclerosis: Therapeutic Innovations and Evolving Regulatory Approaches. (PubMed, CNS Neurol Disord Drug Targets) - "Despite extensive research, riluzole and edaravone remain the only globally approved disease-modifying therapies, offering modest survival benefits...The accelerated approval and subsequent withdrawal of sodium phenylbutyrate-taurursodiol (AMX0035) are discussed as a critical case study highlighting the challenges of regulatory flexibility in rare, fatal diseases. Advances in biomarker development, especially neurofilament light chain, are examined for their growing role in trial design and therapeutic evaluation. Collectively, these insights underscore a shift toward biomarker- informed and precision-based approaches that may improve future ALS therapeutic development."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Respiratory Diseases • NEFL

Amylyx’s ORION Trial in Progressive Supranuclear Palsy Reaches Completion... (The Globe and Mail) - "The study uses a two‑part structure with each part running a 52‑week blinded period followed by an optional 52‑week open‑label extension on AMX0035...The latest update on April 27, 2026 confirms the study’s status as completed on ClinicalTrials.gov, a key inflection point as investors now wait for top‑line results and any follow‑on regulatory steps."

Trial completion • CNS Disorders • Progressive Supranuclear Palsy

ORION: AMX0035 and Progressive Supranuclear Palsy (clinicaltrials.gov) - P2/3 | N=139 | Completed | Sponsor: Amylyx Pharmaceuticals Inc. | Active, not recruiting ➔ Completed | Trial completion date: Nov 2029 ➔ Oct 2025 | Trial primary completion date: Apr 2026 ➔ Sep 2025

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy

HELIOS: AMX0035 in Adult Patients With Wolfram Syndrome (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Amylyx Pharmaceuticals Inc. | Trial completion date: Dec 2026 ➔ May 2028

Trial completion date • Metabolic Disorders • Nephrology

Current and emerging therapeutic strategies for amyotrophic lateral sclerosis: from pharmacological approaches to gene and stem cell therapies. (PubMed, Front Neurol) - "The recent market withdrawal of a previously approved therapy (AMX0035) further underscores the challenges in this field...In addition, the management of ALS symptoms plays a key role in improving the daily lives of people with the disease. In this review, we summarize various strategies for treating ALS, providing an overview of the disease."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies

An oral drug against decline in the autophagy lysosomal pathway (ALP) and systemic inflammation, two "hallmarks" of ALS/FTD (ALS-MND 2025) - "Background: The two drugs against symptoms of syndromic ALS, riluzole and edavarone were approved in 1995 and 2017...After accelerated approval in 2022, the fixed-dose combination PB-TUDCA (Relyvrio) was withdrawn in Apr 2024 based on negative phase 3 results (2)... HP-beta-CD (HPbCD) has been shown to be effective in models of several NDDs and is in phase 3 against NPC, but the presumed MoA of "depleting cholesterol" (CHO) can cause permanent hearing loss. A reanalysis of GWAS data using a patented discovery platform showed that bCDs act by reducing PLs and SLs (4) and, thus, also ceramides (5), which explains how aCDs (too small to fit CHO), were more effective ex vivo in fibroblasts of patients with seven lysosomal storage diseases (LSDs) and in vivo in a SOD1 ALS model (n = 24, ρ<.0001). Improving lysosomal function via HPaCDs, which reduces endocytosis and, thus, lysosomal load, was hypothesized to improve autophagy by preventing lysosomes from both..."

Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Lysosomal Storage Diseases • Metabolic Disorders • Otorhinolaryngology • Rare Diseases • EIF2B4 • RIPK1

Real-World Clinical Experience With Sodium Phenylbutyrate and Taurursodiol at a Single Amyotrophic Lateral Sclerosis Center in the United States. (PubMed, Eur J Neurol) - "Experience in real-world clinical settings can help supplement trial data with information on the drug performance at various stages of disease progression. Adverse events impacted treatment persistence in routine clinical practice, underscoring the need for vigilant monitoring and tailored supportive interventions to optimize treatment adherence."

Journal • Real-world evidence • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Amylyx Pharmaceuticals withdraws FDA approval for Relyvrio treatment. (AInvest)

FDA event • Progressive Supranuclear Palsy

Amylyx Discontinues Investigative Therapy Program In Rare Neurological Disorder (MENAFN news) - "AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol. The decision to discontinue the program was made after it did not show differences compared to placebo on primary or secondary outcomes at week 24 in a mid-stage trial. The company will not initiate the late-stage portion of the program, it said."

Discontinued • Progressive Supranuclear Palsy

Latest progress and challenges in drug development for degenerative motor neuron diseases. (PubMed, Neural Regen Res) - "The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis: riluzole, edaravone, AMX0035, and tofersen, with the latter being the most recent to receive approval. Some promising drugs being investigated in preclinical studies, such as ATH-1105, are included in our analysis, and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases. This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs, with the aim of highlighting the latest potentialities for clinical therapy."

IO biomarker • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies

Amylyx Pharmaceuticals Announces Positive Long-Term Results from Phase 2 HELIOS Clinical Trial of AMX0035 in People with Wolfram Syndrome (Businesswire) - P2 | N=12 | HELIOS (NCT05676034) | Sponsor: Amylyx Pharmaceuticals Inc. | "Treatment with AMX0035 from Week 24 to Week 48 also showed sustained improvements or stabilization in glycemic control, as measured by hemoglobin A1c (HbA1c) and time in target glucose range assessed by continuous glucose monitoring, as well as visual acuity. All participants with available measurements met the responder criteria, defined as either improvement or no change, on both the Patient Global Impression of Change (PGI-C) and Clinician Global Impression of Change (CGI-C) at Weeks 24 and 48, indicating stability or improvement in their Wolfram syndrome-related symptoms....Safety data were consistent with safety data from prior studies of AMX0035."

P2 data • Genetic Disorders

AMX0035 Mitigates Oligodendrocyte Apoptosis and Ameliorates Demyelination in MCAO Rats by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction. (PubMed, Int J Mol Sci) - "The activation of ER stress and mitochondrial dysfunction pathways following MCAO led to oligodendrocyte damage and apoptosis. AMX0035 can inhibit these pathways, reduce oligodendrocyte apoptosis, and alleviate demyelination, thereby improving PSCI."

Journal • Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Cardiovascular • Cognitive Disorders • Metabolic Disorders • Solid Tumor • CASP12 • MBP

HELIOS: AMX0035 in Adult Patients With Wolfram Syndrome (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Amylyx Pharmaceuticals Inc. | Trial completion date: Jan 2026 ➔ Dec 2026

Trial completion date • Metabolic Disorders • Nephrology

Amylyx Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "Unblinded interim analysis of the Phase 2b portion of the Phase 2b/3 ORION trial evaluating AMX0035 for progressive supranuclear palsy (PSP) in the third quarter of 2025. ORION is an operationally seamless Phase 2b/3 clinical trial in people living with PSP. The Phase 2b portion was fully enrolled in January with a total of 139 participants randomized. Amylyx expects safety and efficacy data from an unblinded interim analysis in these participants through Week 24 and will use this data to inform a go/no-go decision on the Phase 3 portion of the trial. Early cohort data from the Phase 1 LUMINA clinical trial of AMX0114 in ALS expected in 2025. LUMINA clinical trial sites were activated in Canada in the beginning of 2025 and are recruiting participants. Amylyx is also working to open U.S. sites for screening, enrollment, and dosing."

P1 data • P2b data • Trial status • Amyotrophic Lateral Sclerosis • Progressive Supranuclear Palsy

Amylyx Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "Completed a public offering of common stock with net proceeds of approximately $65.5 million, extending the company’s cash runway through the end of 2026; Amylyx plans to share Week 48 data from the ongoing Phase 2 HELIOS trial of AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO, also known as ursodoxicoltaurine]) in Wolfram syndrome in the coming months; Unblinded interim analysis of the Phase 2b portion of the Phase 2b/3 ORION trial evaluating AMX0035 for progressive supranuclear palsy (PSP) in the third quarter of 2025."

Commercial • P2 data • Genetic Disorders • Progressive Supranuclear Palsy

Amylyx Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "Completion of enrollment for the pivotal Phase 3 LUCIDITY clinical trial of avexitide in PBH expected in 2025, with a data readout anticipated in the first half of 2026 and, if approved, commercial launch anticipated in 2027....Amylyx plans to share Week 48 data from the ongoing Phase 2 HELIOS trial of AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO, also known as ursodoxicoltaurine]) in Wolfram syndrome in the coming months. Data from participants at Week 48 and regulatory interactions will inform the design of a Phase 3 trial of AMX0035 in Wolfram syndrome."

Launch • P3 data: top line • Trial status • Genetic Disorders • Hypoglycemia

ALS: A Silent Slayer of Motor Neurons. Traditional Chinese Herbal Medicine as an Effective Therapy. (PubMed, Curr Pharm Des) - "Ongoing investigations explore the potential of neuroprotective drugs like riluzole and edaravone in ALS treatment. Recently approved drugs, Relyvrio (sodium phenylbutyrate and taurursodiol) and Tofersen (Qalsody) have completed the trials, and others are currently undergoing extensive clinical trials. Continuous research and exploration of therapeutic avenues, including gene therapy and neuroprotective treatments, are imperative to address the challenges posed by ALS and other neurodegenerative diseases. Traditional Chinese Medicine (TCM) approaches and clinical trials are being explored for treating ALS symptoms, targeting neuroinflammation, oxidative damage, and muscle weakness, showcasing the potential benefits of integrating traditional and modern approaches in ALS management."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Gene Therapies • Inflammation

Extension Study Evaluating The Safety And Tolerability of AMX0035 (clinicaltrials.gov) - P3 | N=352 | Completed | Sponsor: Amylyx Pharmaceuticals Inc. | Enrolling by invitation ➔ Completed | N=600 ➔ 352 | Trial completion date: Aug 2026 ➔ Oct 2024 | Trial primary completion date: Mar 2026 ➔ Oct 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

ORION: AMX0035 and Progressive Supranuclear Palsy (clinicaltrials.gov) - P2/3 | N=110 | Active, not recruiting | Sponsor: Amylyx Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy

Preliminary analysis of treatment combinations in patients with amyotrophic lateral sclerosis enrolled in an US-based administrative claims database (ALS-MND 2024) - "Sodium phenylbutyrate and taurursodiol (PB-TURSO) was FDA-approved in 2022, but voluntarily discontinued in 2024. Tofersen was FDA-approved for patients with ALS with a superoxide dismutase 1 mutation in 2023... Patients with ALS continuously enrolled in Optum's de-identified ClinformaticsV R Data Mart (CDM) from 1 August 2017, through 30 September 2023, were included (intravenous) and Radicava ORSV and grouped based on ALS treatment combination... Patients were grouped based on use of riluzole only (n = 2193) vs. other FDA approved treatment/treatment combinations (n = 967) including Mitsubishi Tanabe Pharma America (MTPA) edaravone, PB-TURSO, riluzole ± edaravone, edaravone ± PB-TURSO, riluzole ± PB-TURSO, or riluzole þ edaravone ± PB-TURSO. Patients were predominantly male (53.5–53.6%), White (72.2–74.4%) and covered by Medicare (68.6–77.8%) rather than commercial insurance."

Claims database • Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders