Abstract-Text (inkl. Referenzen)

Introduction

An oral, fixed-dose sodium phenylbutyrate-ursodoxicoltaurine (AMX0035) combination significantly slowed functional decline (measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised [ALSFRS-R]) in the 24-week randomized, placebo-controlled ALS trial, CENTAUR. Here we report long-term efficacy (overall survival [OS] and function) and safety results.

Methods

Adults with definite ALS (revised El Escorial criteria), ≤18 months from symptom onset and slow vital capacity (SVC) >60%, were randomized 2:1 to AMX0035 or placebo + standard of care (placebo) for 24 weeks. Ninety eligible participants subsequently enrolled in an open-label extension to receive AMX0035 for ≤42 months. OS was assessed at ≤42 months, long-term function/safety at 48 weeks.

Results

Longer OS was observed with AMX0035 compared with placebo (median time to death, 23.5 vs 18.7 months, P=.048), along with longer time to composite/individual outcomes of death, tracheostomy/permanent assisted ventilation, and first hospitalization. At 48 weeks, higher scores for AMX0035 were observed in ALSFRS-R (total, 4.23 points higher, P=.02), upper-limb Accurate Test of Limb Isometric Strength (7.77 points higher; P=.03), and SVC (10.66% higher; P=.04).

Discussion

Earlier initiation and longer duration of AMX0035 were associated with long-term functional and OS benefit. Treatment-emergent adverse events with AMX0035 were primarily gastrointestinal and more common in the first 3 weeks.