Basic neuroscience research has exploded in recent years, particularly within the areas of clinical biology and genetics; however, development of central nervous systems (CNS) therapies has remained limited. Most CNS disorders lack validated molecular targets, and newer treatments are largely variations on already identified mechanisms and pathophysiologic hypotheses.

With a limited understanding of the underlying biology of disease, there is limited development of innovative treatments, leaving the most severe neuropsychiatric disorders without new therapies. To increase likelihood of successful clinical trial outcomes, five main challenges specific to CNS drug discovery and development should be addressed.

1. Heterogeneity of neuropsychiatric disorders requires implementation of additional measures to improve patient homogeneity in trials. Researchers should adopt fluid biomarkers to assess relevant pathophysiology when possible and/or consider new technologies offering new analytical approaches (e.g., circuit-based assessment tools) to assess pathophysiological profiles. Defining domain-related biomarkers when selecting patient population can also assist with patient selection.
2. Efficacy can be addressed through novel target selection that is informed by human neurobiological data, pathophysiological hypotheses, disease-relevant biomarkers and clinical observations.
3. Utilize preclinical models to explore biological disease symptoms, rather than disorders, to identify truly translatable biomarkers.
4. Reliability can be increased by supplementing highly variable, subjective, questionnaire-based endpoints with objective quantitative measures and biomarker-based clinical endpoints. Consider novel technologies that objectively capture digital behavioral data objectively and reproducibly (e.g., assessment of voice cadence, or algorithms capturing emotional response to visual stimuli). Increase clinical efficacy signal detection precision by adopting domain-relevant endpoints.
5. Use alternative modality biomarkers to account for the lack of molecular biomarkers. Reverse translation of neuroimaging and electrophysiology biomarkers to capture neurocircuitry modulation and dysfunction can inform clinical studies.

Our Experience:

• 20+ years of clinical product development
• 20+ years working on CNS project
• 75+ CNS clinical projects
• Product types: Drugs (NCEs, botanicals, biologics, cell therapies, gene therapies), devices and diagnostics
• Clinical trials: 45+ (Phase I-III), 315+ sites, 4,035+ patients; proof of concept through FDA marketing approval
• Regulatory services: Multiple OCP, IND, NDA application submissions, one BLA application submission and one ODD application submission
• Full scope projects and targeted scope projects
• Helped clients obtain five NDA CNS market approvals

Therapeutic Indications:

• Addiction
• Adolescent schizophrenia
• Adult schizophrenia
• Alzheimer’s disease
• Amyotrophic lateral sclerosis (ALS)
• Anesthetic
• Attention-deficit/hyperactivity disorder (ADHD)
• Chronic complete spinal cord injuries (SCIs)
• Huntington’s disease
• Ischemic stroke and AIS-A complete chronic spinal cord injury (cSCI)
• Major depressive disorder (MDD)
• Mild dementia due to Alzheimer’s disease
• Pain management (acute/chronic)
• Parkinson’s disease
• Pediatric ADHD
• Polyglutamine spinocerebellar ataxia
• Post-herpatic neuralgia
• Restless leg syndrome
• Sedation
• Severe myoclonic epilepsy in infancy (SMEI)
• Smoking cessation
• Spinal bulbar muscular atrophy (SBMA)
• Stroke (acute/chronic)
• Traumatic brain injury (TBI)
• Treatment-refractory schizophrenia (TRS)