The US Food and Drug Administration (FDA) has approved the combination oral medication of sodium phenylbutyrate and taurursodiol (Relyvrio) to treat individuals with amyotrophic lateral sclerosis (ALS).
ALS is a fatal neurodegenerative disease, characterized by the loss of motor neurons in the central nervous system, leading to paralysis and early death. The most frequent genetic cause of ALS is the expansion of hexanucleotide GGGGCC repeats in the first intron of the C9ORF72 gene. These repeats lead to sense and antisense transcriptions that are believed to be part of the pathophysiology of ALS.
Sodium phenylbutyrate and taurursodiol is an oral fixed-dose medication designed to possibly reduce neuronal cell death by simultaneously mitigating endoplasmic reticulum (ER) stress and mitochondrial dysfunction.
The FDA approval was largely based on data from a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in which 137 adult patients with ALS were randomized to receive either sodium phenylbutyrate–taurursodiol or placebo.
That study, published in the New England Journal of Medicine, met its primary outcome measure – the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Patients treated with sodium phenylbutyrate–taurursodiol had a decline of -1.24 points per month in their ALSFRS-R mean score compared to -1.66 in the placebo group (P = .03).
The most common adverse were diarrhea, abdominal pain, nausea and upper respiratory tract infection. It should be noted that the medication contains taurursodiol, a bile acid, which may cause worsening diarrhea in patients with disorders that interfere with bile acid circulation.
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