Sodium Phenylbutyrate Taurursodiol (Relyvrio) For Als is a treatment approach for neurodegenerative diseases. This page provides comprehensive information about its mechanism of action, clinical evidence, and therapeutic potential.
Sodium phenylbutyrate/taurursodiol (Relyvrio®; also known as AMX0035) is an FDA-approved combination therapy for amyotrophic lateral sclerosis (ALS). Approved in 2022, Relyvrio represents a novel approach to ALS treatment by targeting multiple pathological pathways simultaneously.[1] The drug was developed by Amylyx Pharmaceuticals and represents one of the few disease-modifying therapies available for ALS, alongside riluzole, edaravone, and antisense oligonucleotides (tofersen for SOD1-associated ALS).
Relyvrio combines two compounds with complementary mechanisms that target both endoplasmic reticulum (ER) stress and mitochondrial dysfunction—two central pillars of ALS pathogenesis:
The combination provides synergistic neuroprotection by:
The CENTAUR trial (NCT03000196) was a landmark study that led to Relyvrio's approval:
The confirmatory Phase 3 PHOENIX trial (NCT05021536) was designed to confirm efficacy:
Exploratory biomarker analyses from clinical trials showed:
| Parameter | Sodium Phenylbutyrate | Taurursodiol |
|---|---|---|
| Bioavailability | ~40% | ~60% |
| Protein binding | >90% | >95% |
| Metabolism | Liver (β-oxidation) | Liver (conjugation) |
| Half-life | ~2 hours | ~4 hours |
| Time to peak | 1-2 hours | 2-4 hours |
| Excretion | Renal (80%) | Biliary (70%) |
| CNS penetration | Moderate | Low-moderate |
Relyvrio's unique mechanism makes it a candidate for combination approaches:
The study of Sodium Phenylbutyrate Taurursodiol (Relyvrio) For Als has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
FDA. "FDA Approves New Drug for Treatment of Amyotrophic Lateral Sclerosis." September 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-amyotrophic-lateral-sclerosis ↩︎
Ryu H, et al. "Sodium phenylbutyrate rescues dopaminergic neurons from oxidative stress." Ann Neurol. 2004;56(2):215-223. PMID:15293284 ↩︎
Iorio R, et al. "Tauroursodeoxycholic acid: a candidate therapeutic for ALS." J Neurol Sci. 2003;206(1):79-83. PMID:12559405 ↩︎
Paganoni S, et al. "Trial of Sodium Phenylbutyrate-Taurursodiol for ALS." N Engl J Med. 2020;383(6):519-527. PMID:32640126 ↩︎
Paganoni S, et al. "Primary results of CENTAUR." ALS Frontotemporal Degener. 2020;21(Suppl 1):50-51. ↩︎
Paganoni S, et al. "Longer-term survival of AMX0035." Neurology. 2021;96(15 Supplement):S50. ↩︎
Amylyx Pharmaceuticals. "PHOENIX Trial Results." March 2024. https://www.amylyx.com ↩︎
冲本 R, et al. "Biomarker analyses from CENTAUR trial." ALS. 2022;23(Suppl 1):67-68. ↩︎
Relyvrio Prescribing Information. Amylyx Pharmaceuticals. 2024. ↩︎
Cudkowicz M, et al. "The future of ALS treatment." Nat Rev Neurol. 2023;19(10):617-628. ↩︎