Relyvrio (AMX0035) for ALS
Also known as: AMX0035, sodium phenylbutyrate-taurursodiol
A combination therapy targeting both ER stress and mitochondrial dysfunction — two key pathological pathways in ALS motor neuron death.
Mechanism of Action
Relyvrio combines sodium phenylbutyrate (a histone deacetylase inhibitor that reduces ER stress by acting as a chemical chaperone) with taurursodiol/TUDCA (which stabilizes mitochondrial membranes and inhibits BAX-mediated apoptosis). The dual-target approach addresses both protein misfolding and mitochondrial failure.
General mechanism: Dual-target: sodium phenylbutyrate reduces ER stress; taurursodiol stabilizes mitochondrial membranes.
Current Evidence
The CENTAUR trial showed slower functional decline (ALSFRS-R) over 24 weeks. PHOENIX confirmatory trial did not meet its primary endpoint, leading to voluntary market withdrawal in 2024. The scientific rationale for dual-pathway targeting remains valid.
Clinical Status: FDA-approved (2022), voluntarily withdrawn (2024) after PHOENIX trial. Research into the dual-target approach continues.
Safety Profile
GI side effects (diarrhea, nausea) are common. Generally well-tolerated in clinical trials.
Key Research Questions
- Can the sodium phenylbutyrate + TUDCA combination be optimized for better efficacy?
- Which ALS subtypes showed the strongest response in CENTAUR?
- Does the dual ER stress + mitochondrial approach have potential in other neurodegenerative diseases?