February 17, 2025

expert reaction to four papers trialling treatments for ALS within the HEALEY ALS Platform Trial

Four papers published in JAMA, JAMA Neurology and JAMA Network Open look at Amyotrophic Lateral Sclerosis (ALS) treatment results from the HEALY ALS Platform Trial. 

Dr Ahmad Al Khleifat, Senior Research Fellow, King’s College London, said:

“Currently, only a few disease-modifying drugs, such as riluzole and edaravone, are approved for ALS, but their benefits are limited. Platform trials, like the HEALEY ALS Platform Trial, provide a faster and more cost-effective way to test multiple treatments simultaneously, cutting the time to identify effective therapies in half and reducing costs by a third. The latest studies from the HEALEY ALS Platform Trial highlight the efficiency of this approach in accelerating drug testing, laying the groundwork for future breakthroughs despite the initial negative results.

“While these outcomes may seem discouraging, they provide critical insights. Randomised clinical trials remain the gold standard for evaluating new treatments, ensuring that observed effects are real rather than influenced by external factors. However, patient recruitment bias can be a challenge, when only a few trials are available, longer-term survivors may be overrepresented, potentially affecting trial design and interpretation.

“Another consideration is the reliance on survival and functional scores as primary outcome measures, rather than biomarkers like neurofilament, which offer a more precise way to track disease progression. Some treatments, such as riluzole and tofersen, have shown benefits only in later stages, meaning shorter trials may overlook their full impact. Extending trial durations or incorporating post-trial follow-ups could help capture these delayed effects and provide a clearer picture of treatment efficacy.

“Despite these challenges, platform trials continue to revolutionise ALS research, they hold immense potential to accelerate the discovery of effective therapies and bring new hope to the ALS community.”

‘Verdiperstat in Amyotrophic Lateral Sclerosis’ by the Writing Committee for the HEALEY ALS Platform Trial was published in JAMA Neurology at 16:00 UK time on Monday 17th February.

DOI: 10.1001/jamaneurol.2024.5249

‘Pridopidine in ALS’ by the Writing Committee for the HEALEY ALS Platform Trial was published in JAMA at 16:00 UK time on Monday 17th February. 

DOI: 10.1001/jama.2024.26429

‘CNM-Au8 in Amyotrophic Lateral Sclerosis’ by the Writing Committee for the HEALEY ALS Platform Trial was published in JAMA at 16:00 UK time on Monday 17th February. 

DOI: 10.1001/jama.2024.27643

‘Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis’ by Paganoni et al., was published in JAMA Network Open at 16:00 UK time on Monday 17th February. 

DOI: 10.1001/jamanetworkopen.2024.59058

Declared interests:

Dr Ahmad Al Khleifat “I am a consultant for NESTA (innovation agency for social good).”