New Thinking on Clinical Trial Endpoints for Drug Development

When you take a medication, you’re likely thinking about how it will improve your daily life. Will it ease your pain? Will it help you sleep better? Will it last throughout your workday? But those considerations – so critical for patients – don’t necessarily map to how drugs are approved, especially in Parkinson’s Disease.

In clinical trial testing, drugs are approved based on their ability to meet a pre-determined endpoint – an objective measure to determine whether the intervention is beneficial. In Parkinson’s drug development, these endpoints have relied heavily on existing scales used in the clinic to measure how patients feel or function, such as the MDS-Unified Parkinson’s Disease Rating Scale (MDS_UPDRS).

But as many patients know, scales like MDS_UPDRS can be unreliable, and can ignore what matters most to them. Despite this common mismatch with patients’ needs, the accepted endpoints and scale used are a roadmap for how companies design clinical trials and get new treatments approved.

One challenge identified with using these measures in drug development is that they focus on leaps in progression seen in later disease rather than subtle, early changes. So, how can drug developers better improve testing of potential treatments aimed at slowing or stopping disease progression in early Parkinson’s, a time when most individuals aren’t seeing significant day-to-day progression of their symptoms?

In a shift that will address the needs of patients with early-stage PD, and ultimately lead to smarter, faster and less-expensive drug development, regulators in both the U.S. and Europe are turning their attention to what is appropriate to use as a measure of efficacy in trials targeting PD. This is a game-changing opportunity for companies designing late-stage trials of interventions in people with early PD because as it stands today, without sensitive endpoints, there is no way to tell if a drug is working in the typical time a trial is run.

MJFF is addressing this need for sensitive, patient-centered endpoints head-on and approaching the issue from two angles – coalescing the field around a shared understanding of what is meaningful to patients and bringing together key stakeholders in a precompetitive setting to develop a roadmap.

MJFF has established in interdisciplinary patient-centered PD Endpoints Advisory Committee of experts from within and outside of the field. Last November, MJFF co-hosted a roundtable with Parkinson’s UK and Parkinson Canada to unite industry and academic groups working on new measure development with representatives from the U.S. Food and Drug Administration.

MJFF is also leveraging the Parkinson’s Progression Markers Initiative (michaeljfox.org/ppmi) infrastructure to collect data and validate novel patient-reported outcomes. One such study is asking patients and care partners about their experience with Parkinson’s in three domains: what’s bothersome, limiting and important.

At MJFF, the organization is working to convene the greatest scientific minds and bring them into direct partnerships with patients. Ultimately, it is these conversations that are critical to unlocking the early signs for PD, developing new scales to track changes over time and ultimately, intervening before the disease ever develops.

Source: Mehlhorn, Kat. Focus on the Patient: New Thinking on Clinical Trial Endpoints is Next Boon for Drug Development. Fox Focus. Spring/Summer 2023. Pages 8-9.