International Alliance of ALS/MND Associations

TUDCA Trial

Background

Tauroursodeoxycholic acid (TUDCA) is an acid present in the bile regularly produced in the human liver. TUDCA is commonly used for treatment of chronic liver conditions and for gallstone and it is thought to have a beneficial effect on mitochondria health (ref: Hoffman 1999). TUDCA has also been described as a protective agent for cellular cell death, and therefore, considered for the treatment of neurodegenerative diseases (ref: Amaral et al., 2009).

Trial Design & Results

A phase 2b proof of concept double blind placebo-controlled study was run in Italy from 2008 to 2012 on 34 individuals affected by ALS/MND. The trial enrolled earlystage non severely disabled individuals who were treated with 1g twice daily of TUDCA or placebo for 54 weeks and examined every 6 weeks. The primary outcome measure was the portion of responder individuals, defined as those showing an improvement of at least 15% in the ALS functional rating scale revised (ALSFRS-R) slope during treatment period compared to the lead in period (the stage before the start of the trial). The study reported that TUDCA was well tolerated, and that the portion of responders was higher in the TUDCA treated group compared to placebo, resulting in slower progression in the TUDCA treated group (ref: Elia et al., 2015). However, this study was conducted on a relatively small number of individuals and a phase 3 was necessary to confirm TUDCA efficacy in slowing disease progression.

On the basis of the results of the phase 2b study, a larger multi center phase 3 placebo-controlled trial was designed using the same dosage of TUDCA and placebo. The trial aimed to recruit 440 people newly diagnosed with ALS in 26 centers across Italy, Germany, UK, France, the Netherlands and Ireland. The delivery of the trial was impacted by the COVID-19 pandemic and recruitment was less than planned. The results from this trial were released in March 2024, the study ran for 18 months including a total of 336 people but failed to meet its primary endpoint, which was defined as a difference in responding and nonresponding individuals in month 18 as measured by ALSFRS-R. Additionally, no difference was found between TUDCA and placebo in secondary outcome measures including time of survival and biomarker measurements. Treatment with TUDCA was well tolerated and generally safe (ref: TUDCA-ALS).

TUDCA is also one of the two components of AMX0035, a compound developed by Amylyx Pharmaceuticals that was recently announced to have not met either primary or secondary endpoints in a phase 3 clinical trial (ref: Amylyx press release).

Summary

Considering the available evidence, it is the opinion of the SAC that TUDCA is safe and tolerable. Given the available data, however, it is the opinion of the SAC that there is enough evidence to conclude that at the studied dosage, TUDCA did not show overall benefit in individuals living with ALS.

International Alliance of ALS/MND Associations
September 2024

The original language of communication is English and any translation cannot be guaranteed for accuracy of messaging.

SOURCES