Parkinson's disease (PD) therapeutic development is shifting towards neuroprotective and disease-modifying therapies (DMTs) to address the limitations of current treatments, which primarily focus on motor symptoms. A GlobalData analysis reveals that a significant portion of the PD pipeline in the seven major markets (7MM) is dedicated to DMTs and therapies targeting non-motor symptoms, reflecting a commitment to addressing the full spectrum of patient challenges.
Emphasis on Disease-Modifying Agents
According to GlobalData, there are 93 products in Phase I-III development for PD in the 7MM, with 66% classified as prospective neuroprotective agents or DMTs. These investigational agents target key mechanisms implicated in the pathophysiology of PD, such as alpha-synuclein aggregation and neuroinflammation, with the goal of slowing disease progression.
Lorraine Palmer, Pharma Analyst at GlobalData, noted that these agents aim to slow disease progression by targeting mechanisms like alpha-synuclein aggregation and neuroinflammation.
Examples of neuroprotective/DMT agents in late-stage development include Annovis Bio’s Posiphen (buntanetap tartrate), a Phase III asset designed to inhibit alpha-synuclein aggregation, and BioVie’s Triolex (bezisterim), an inhibitor of inflammatory mediators, which has a Phase III trial planned based on its neuroprotective potential.
Alpha-Synuclein Target
Notably, 26% of the DMT pipeline targets alpha-synuclein aggregation. However, this mechanism of action is viewed with mixed opinions within the field. While some key opinion leaders (KOLs) hold high hopes, others express skepticism, referencing the failure of Prothena and Roche’s prasinezumab in the Phase II PASADENA trial (NCT03100149) and safety concerns related to alpha-synuclein's role in healthy functioning.
Addressing Non-Motor Symptoms
KOLs interviewed by GlobalData emphasized the need for research focused on DMT development, while also highlighting that the pathogenesis of PD can vary across patients. They expressed enthusiasm for therapies addressing falls and non-motor PD symptoms, recognizing a significant unmet need in these areas.
18% of the pipeline is classified as 'other antiparkinsonian agents,' focusing on symptom management beyond core motor symptoms. Examples include Cerevance’s solengepras (Phase III; NCT06553027), which aims to improve postural instability in PD patients; IRLAB’s Pirepemat (Phase IIb; NCT05258071), under investigation for both postural instability and PD-dementia; and Silo Pharma’s psilocybin (Phase II), targeting depression and anxiety in PD patients.
3% of the pipeline specifically targets PD-dementia and PD-psychosis. This research, along with development into other antiparkinsonian agents, dopamine agonists, and treatments for PD-related dementia, indicates a comprehensive research outlook aimed at improving both motor and non-motor symptoms.
Palmer concludes that the distribution of the 93 pipeline agents in the 7MM underscores a strong emphasis on neuroprotective and disease-modifying treatments, demonstrating an industry-wide focus toward therapies that could potentially slow the progression of PD.
