Relyvrio (sodium phenylbutyrate/taurursodiol, also known as AMX0035) is a combination therapy approved by the FDA in 2022 for the treatment of amyotrophic lateral sclerosis (ALS)[1]. This dual-agent therapeutic targets multiple pathological pathways in ALS, including endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and oxidative stress[2].
The drug combines two active compounds:
This combination represents a novel approach to ALS treatment by simultaneously addressing multiple interconnected pathological mechanisms[3].
Sodium phenylbutyrate is a small-molecule compound that acts as a chemical chaperone:
Taurursodiol (tauroursodeoxycholic acid) is a bile acid with potent mitochondrial protective effects:
The combination of NaPBA and TUDCA provides synergistic benefits by:
The CENTAUR trial (NCT03127514) was a randomized, double-blind, placebo-controlled study[6]:
Results:
Common adverse events included:
Most adverse events were mild to moderate and did not lead to treatment discontinuation.
| Parameter | Details |
|---|---|
| Sodium Phenylbutyrate | 3 g/m² twice daily (approximately 12 g/day for average adult) |
| Taurursodiol | 1 g twice daily |
| Route | Oral (powder for suspension) |
| Administration | Mix with water or soft food, take with or without food |
| Duration | Chronic, long-term treatment |
| Region | Status | Year |
|---|---|---|
| US (FDA) | Approved | 2022 |
| EU (EMA) | Under review | — |
| Canada | Approved | 2023 |
| Japan | Under review | — |
Relyvrio received FDA approval in September 2022 under the FDA's Animal Efficacy Rule, based on substantial evidence of effectiveness from animal models combined with human safety data[7].
| Feature | Relyvrio | Riluzole | Edaravone |
|---|---|---|---|
| Target | ER/mitochondrial dysfunction | Glutamate excitotoxicity | Oxidative stress |
| Efficacy | ~25% slower decline | ~20% survival benefit | ~30% slower decline |
| Route | Oral | Oral | IV infusion |
| Dosage | Twice daily | Twice daily | Daily (cycles) |
| Approval | 2022 | 1995/2017 | 2017/2023 |
Relyvrio can be combined with other ALS therapies:
Ongoing trials are exploring these combinations.
Research is ongoing to identify:
Saxena S, et al. AMX0035, a combination of sodium phenylbutyrate and taurursodiol, for the treatment of ALS. Expert Opin Pharmacother. 2023. ↩︎
Pupillo E, et al. Sodium phenylbutyrate/taurursodiol (AMX0035): a new therapeutic approach for ALS. Neurol Sci. 2022. ↩︎
Ryu H, et al. Sodium phenylbutyrate in ALS: from bench to bedside. Ann Neurol. 2004. ↩︎
Castro-Caldas J, et al. Tauroursodeoxycholic acid prevents neuronal death in a rat model of perinatal asphyxia. Neuropharmacology. 2020. ↩︎
Paganoni S, et al. Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis. N Engl J Med. 2020. ↩︎