The CENTAUR phase 2, randomised, placebo-controlled trial included patients with amyotrophic lateral sclerosis (ALS) who received a fixed dose formulation of sodium phenylbutyrate-taurursodiol (PB-TURSO). The trial showed results of a slowed functional decline.
Background
ALS has two US Food and Drug Administration approved disease-modifying treatments, edaravone and riluzole. The effects on survival of edaravone are unknown while Riluzole has shown increased survival. PB-TURSO slows the neuronal death by reducing mitochondrial dysfunction and endoplasmic reticulum stress in the pathogenic factors of ALS.1 The trial included patients aged 18 to 80 years, with a diagnosis of ALS, and upper and lower motor neuron signs in three regions, with onset of symptoms within the last 18 months.1 Patents were randomised 2:1 PB-TURSO (delivered in a 3g PB and 1g TURSO sachet) or matching placebo by mouth or a feeding tube twice a day for 6 months.1
Results
A total of 138 participants were randomised, 89 received PB-TURSO and 48 received placebo. Most patients (77%) were taking either riluzole or edaravone prior or at the start of the trial.1 The trial lasted 24 weeks (6 months). Patients originally in the treatment or control groups could then enter an open label extension (OLE) to receive the drug for up to 132 weeks (30 months).1 Patients taking the active treatment had a 44% lower chance of death compared to those originally randomised to the placebo (HR 0.56, P= 0.023).1 Participants had a median PB-TURSO exposure duration of 8.8 months who were originally randomised to treatment, and a median PB-TURSO exposure of 1.9 months (in the OLE) for those originally randomised to placebo. The overall survival rate was calculated from all randomised participants, including those who joined the OLE and those discontinued or were lost to follow up.1 The median survival of all the PB-TURSO participants was 25.0 months (95% CI, 19.0–33.6) and the median survival of those originally in the placebo group was 18.5 months (95% CI, 13.5–23.2).1
Early initiation of BP-TURSO treatment in participants with ALS yield a long-term survival benefit alongside previously demonstrated functional benefit.
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