Transforming ALS drug development : the power of complex innovative trial designs

Abstract

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder with limited treatment options, underscoring the need for efficient trial designs to accelerate drug development. Traditional randomized controlled trials (RCTs), which focus on a single investigational treatment per study, are often inadequate for ALS due to slow enrollment and high costs. Adaptive platform trials (APTs) provide a transformative approach, enabling multiple treatments to be tested simultaneously under a master protocol. This structure supports the shared use of control groups and allows treatments to enter or exit the trial based on interim analysis. The HEALEY ALS Platform Trial exemplifies this model, utilizing a Bayesian approach for integrated assessment of treatment efficacy and survival outcomes, thus enhancing efficiency and flexibility. By sharing a control arm across treatment groups and employing adaptive randomization, the HEALEY trial reduces sample size requirements and accelerates results. Despite initial setup complexity and substantial upfront investment, APTs hold great potential for advancing ALS research and could become standard in neurology and rare disease studies. The HEALEY ALS Platform Trial serves as a model for future neurodegenerative disease trials, offering a sustainable and patient–centered approach to rapid therapeutic evaluation.