An evaluation of the combination of sodium phenylbutyrate and taurursodiol for the treatment of amyotrophic lateral sclerosis

ABSTRACT

Introduction

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative motor neuron disease. Despite the overwhelming need for effective therapeutics for ALS, riluzole and edaravone were the only two FDA-approved disease-modifying therapies prior to 2022. The randomized, double-blind, multicenter, placebo-controlled CENTAUR trial demonstrated the safety and efficacy of sodium phenylbutyrate-taurursodiol (PB-TURSO) in persons with ALS (PALS), leading to its conditional approval in Canada in June 2022 and full approval in the USA in September 2022.

Areas covered

Herein, the authors provide a review of the pharmacology and clinical trials evaluating sodium phenylbutyrate and/or taurursodiol in PALS.

Expert opinion

The safety and tolerability of both PB and TURSO were previously demonstrated in small PALS trials. The phase 2 CENTAUR study and its open-label extension demonstrated the safety and efficacy of AMX0035 (a sachet containing a fixed co-formulation of 3 g of PB and 1 g of TURSO given twice daily) in PALS. A phase 3 PHOENIX trial (NCT05021536) will offer more insight into safety and efficacy of AMX0035. AMX0035 currently costs $ 158,000 annually in the US, which may become a financial barrier for PALS to receive the medication.

KEYWORDS:

• AMX0035
• amyotrophic lateral sclerosis
• PB-TURSO
• sodium phenylbutyrate
• taurursodiol

Article highlights

• Both sodium phenylbutyrate (PB) and taurursodiol (TURSO) were previously demonstrated to be safe and tolerable in small PALS trials, and the TURSO trial was suggestive of a benefit.

• The phase 2 CENTAUR study and its open-label extension study demonstrated the safety and efficacy of AMX0035 (a sachet containing fixed-dose co-formulation of 3 g of PB and 1 g of TURSO given twice daily) in PALS.

• Based on the result of the phase 2 CENTAUR study, AMX0035 was conditionally approved in Canada in June 2022 (marketed as Albrioza) and was fully approved in the USA in September 2022 (marketed as Relyvrio).

• A phase 3 PHOENIX trial aiming to enroll 600 PALS (NCT05021536) to evaluate the safety and efficacy of PB-TURSO has recently completed its recruitment.

• AMX0035 currently costs $158,000 per year in the US, comparable to oral edaravone ($171,000 per year), which may become a financial barrier for PALS to receive the medication.

Declaration of interest

R Bedlack receives research support from ALSA, Orion, MediciNova, and the Healey Center. He also receives consulting support from AB Science, Adept Field Solutions, Alexion, ALSA, Amylyx, Apellis, Biogen, Black Swan, Brainstorm Cell, Clarivate, Clearview, Clene, CM Group, Corcept, Cytokinetics, GenieUs, Guidepoint, Health Advances, IQVIA, ITF Pharma, MallinkrodtMallinckrodt, MJH Healthcare, Maple Healthcare, MT Pharma America, National Association of Managed Care Physicians, Neurosense, New Biotic, Orphazyme, PTC Therapeutics, Projects in Knowledge, Shinkei, Springer Publishing, UCB Pharma, UMA Education, WebMD Health, and Woolsey Pharma. He is a speaker for Amylyx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.