Can Innovative Trial Designs in Orphan Diseases Drive Advancement of Treatments for Common Neurological Diseases?

Abstract

Global regulatory agencies have transformed their approach to approvals in their processes for formal review of the safety and efficacy of new drugs. Opportunities for innovation have expanded because of the coronavirus disease 2019 (COVID-19) pandemic. Several regulatory-led initiatives have progressed rapidly during the past year, including patient-focused drug development, model-informed drug development, real-world evidence, and complex innovative trial designs. Collectively, these initiatives have accelerated the rate of approvals. Despite demands to focus on urgent needs imposed by the COVID-19 pandemic, the number of new drug approvals over the past year, particularly for rare diseases, has outpaced expectations. Advancing therapeutics for nervous system disorders requires adaptive strategies that align with rapid developments in the field. Three relentlessly progressive diseases, amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and Parkinson's disease are in urgent need of new treatments. Herein, we propose new regulatory initiatives, including innovative trial designs and patient-focused drug development that accelerate clinical trial conduct while meeting critical regulatory requirements for therapeutic approval.

Figure 1

Diagram highlighting examples of regulatory innovation, policy, and drug development in ALS, DMD, and PD. *Targets with shared mechanisms of action: oxidative stress, inflammation, mitochondrial stabilization, modulation of calcium homeostasis, restoration of energy homeostasis, stress response modulation, and growth factors. ALS, amyotrophic lateral sclerosis; DMD, Duchenne muscular dystrophy; EHR, electronic health record; PD, Parkinson’s disease.

Figure 2

The Critical Path Institute (C‐Path)’s rare disease cures accelerator data analytics platform (RDCA‐DAP) houses integrated patient‐level data from diverse sources, including clinical trials, longitudinal observational studies, patient registries, and real‐world data (e.g., electronic health records) across a multitude of rare diseases. Data are contributed from different organizations and companies around the world. Deidentified data is standardized, integrated, and analyzed to support regulatory endorsement of drug development tools.