Currently Enrolling Trials
Relyvrio is a proprietary oral fixed-dose combination of two small molecules: sodium phenylbutyrate (PB), a small molecular chaperone and taurursodiol, a Bax inhibitor.
Relyvrio is specifically indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults.
Relyvrio is supplied as an oral suspension. The recommended initial dosage for oral suspension is 1 packet (3 g sodium phenylbutyrate and 1 g taurursodiol) daily for the first 3 weeks. After 3 weeks, increase to the maintenance dosage of 1 packet twice daily.
Preparation and Administration:
- Empty contents of one packet in a cup containing 8 ounces of room temperature water and stir vigorously. Take orally or administer via feeding tube within 1 hour of preparation. The reconstituted suspension may be stored for up to 1 hour at room temperature. Discard any unused reconstituted suspension after 1 hour. Administer Relyvrio before a snack or meal.
Mechanism of Action
Relyvrio is a proprietary oral fixed-dose combination of two small molecules: sodium phenylbutyrate (PB), which is a small molecular chaperone designed to reduce the unfolded protein response (UPR), preventing cell death resulting from the UPR, and taurursodiol (TURSO; also known as ursodoxicoltaurine), which is a Bax inhibitor designed to reduce cell death through apoptosis. PB and TURSO were combined in a fixed-dose formulation in an effort to reduce neuronal death and dysfunction. AMX0035 is designed to target the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.
Adverse effects associated with the use of Relyvrio may include, but are not limited to, the following:
- abdominal pain
- upper respiratory tract infection
Clinical Trial Results
The FDA approval of Relyvrio was based on data from CENTAUR, a multicenter Phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized, placebo-controlled phase and an open-label extension (OLE) long-term follow-up phase. In this trial, participants receiving AMX0035 demonstrated statistically significant reduction in clinical decline at the end of the 6-month randomized phase, as measured by the Revised ALS Functional Rating Scale (ALSFRS-R). In a survival analysis conducted in all patients who were followed for up to three years, which included participants who continued to receive AMX0035 in an open-label extension phase during the follow-up period, patients who started on AMX0035 during the placebo-controlled phase of CENTAUR demonstrated a 44% lower risk of death compared to those who started on placebo. Median survival duration through the open-label long-term follow-up phase was 25 months in the group that started on AMX0035 and 18.5 months in the group that started on placebo.
A post-hoc analysis of data suggested a larger survival benefit for AMX0035 when adjusting for placebo crossover ranging from 10.6 to 18.8 months compared with 6.9 months seen in the original prespecified intent-to-treat (ITT) analysis.