Despite substantial investment, an annual report from Cure Parkinson’s highlights that the progression of disease-modifying therapies (DMTs) from Phase 2 to Phase 3 remains limited. Recognizing the need to break through this impasse via its Biomarker Advancement Programs, the Michael J. Fox Foundation’s Imaging Program specifically targets imaging-based solutions. MRI biomarkers, in particular, represent a valuable - albeit underused - asset in the PD clinical development toolkit. Read on to find out why!
MRI biomarkers can provide objective, reproducible and quantifiable evidence of treatment effects at both the group and individual level. They can serve as standalone indicators of efficacy, or complement more traditional endpoints such as clinical scales, making results less open to subjective interpretation. These qualities resonate with regulatory agencies: in fact, in an encouraging move, the FDA released guidance to assist and support the use of imaging data in trials as primary or component endpoints. By including such endpoints, sponsors stand to accelerate regulatory timelines and fast track their shot at approval.
PD is a heterogeneous disease comprising diverse clinical phenotypes, and also includes atypical parkinsonian syndromes with overlapping but distinct features. Complicating matters further, trials must take into consideration the confounding effects of existing symptomatic medication such as levodopa, among others. Evidence suggests that several MRI biomarkers have the ability to both distinguish between PD subtypes and predict response to therapy. This could be indispensable for patient stratification efforts. To reinforce this point, any improvement in patient selection would inevitably enhance statistical power, meaning smaller sample sizes and lower long-term study costs.
Cure Parkinson’s annual report suggested that the limited transition of DMTs from Phase 2 to Phase 3 may stem from an incomplete understanding of PD biology. MRI biomarkers are already helping to fill this gap by offering an in vivo view of PD pathophysiology and therapeutic effects. In slowly progressing diseases like PD - where clinical manifestations are preceded by a prodromal phase - highly sensitive imaging biomarkers can detect subtle longitudinal changes that clinical scales may miss.
MRI data acquisition is becoming increasingly standardized, and is in fact already fairly routine in the general trial space for safety monitoring. This has created a scalable foundation for broader use of imaging biomarkers in multi-center studies. Sponsors can even amplify the return on investment of scaling by repurposing existing, high quality datasets for retrospective analyses. Together, scalability and reusability go hand-in-hand to make MRI an impactful asset for maximizing long-term trial value.
In a competitive clinical trial landscape, MRI biomarkers offer a strategic way to stand out. Studies employing cutting edge yet evidence-based technologies likely yield more high-impact publications and attract early-stage investments. While sophisticated technologies such as MRI can be complex from an analytical and logistical point of view, QMENTA can provide the infrastructure and medical imaging expertise required to enable sponsors to fully leverage them.
Minimize costs and maximize efficiency by incorporating MRI biomarkers into your next Parkinson’s Disease study.
For more thoughts and practical use cases - including which imaging biomarkers to prioritize first - access the extended Parkinson’s Disease eBook in our The Imaging Edge series