ROCHE HD DIGITAL MONITORING PLATFORM
Supporting Clinical Assessments of Huntington’s Disease
The desire and necessity for digital, at-home healthcare technology was accelerated by the global pandemic, but companies like Roche have been preparing for this tipping point for many years. Roche initially developed a smartphone- and smartwatch-based digital monitoring platform for people with Parkinson’s disease and multiple sclerosis. They realized its potential for other neurological diseases and adapted and integrated it into clinical trials for people with Huntington’s disease (HD) to test if it could reliably collect and evaluate data on disease symptoms, to complement the information that is gathered at clinic visits.
Historically, the clinical assessment of HD primarily relies on periodic in-person visits and administration of clinician-rated measures. However, the infrequency of these assessments can result in subtle changes in signs and symptoms of the disease going unnoticed or without understanding the daily context in which people experience them.
Roche’s remote HD digital monitoring platform (HD dMP) was designed to assess motor, cognitive, and functional domains in HD using frequent active and continuous passive monitoring. The active tasks include questionnaires, upper body motor tests such as speeded tapping, stability and walking tests, and cognitive tests such as word reading. Passive monitoring continuously monitors chorea, walking tests, and activity levels throughout a person’s daily life.
The HD dMP was implemented into multiple studies of the tominersen clinical trial program in manifest HD as well as Digital HD, an observational study led by Professor Ed Wild at the UCL Huntington’s Disease Centre, a cohort including healthy volunteers, premanifest and manifest HD. Across these studies, more than 1,000 people with HD across 18 countries and five continents have contributed data via the HD dMP.
The collection of such a large data set demonstrates the practical feasibility of integrating the HD dMP into both observational and interventional clinical trials. It is also hoped that the tool will provide data to support the assessment of efficacy of novel therapies in development for HD.
This year at CHDI 2022, Jonas Dorn Ph.D., Digital Biomarker Lead for Huntington’s Disease at Roche, presented HD dMP results from the Phase III GENERATION HD1 trial, in which dosing was stopped early due to overall benefit-risk considerations. The HD dMP data showed overall good adherence in this large Phase 3 study, with >50% of patients completing the minimum number of tests required at 69 weeks. However, it transpired that in the placebo arm, those with HD who stopped collecting digital data did worse, on average, than the people with HD who continued to collect digital data. This means that the digital data in the placebo arm was biased toward slower disease progression, which in turn means that placebo cannot be meaningfully compared to treatment arms to assess the efficacy of tominersen treatment in this trial.
Further analyses were shared by Dr. Dorn at the recent European Huntington’s Disease Network Plenary Meeting (EHDN 2022) in September that help to characterize the people with HD who dropped out of the digital data collection prematurely. It appeared that people with more advanced HD at baseline stopped collecting digital data earlier, suggesting that the burden from the assessment may have been too high. These findings, together with other insights, will help the team to improve the HD dMP digital data collection in trials.
Dr. Dorn also showed initial results suggesting that data from a single test, speeded tapping, detected disease progression earlier than a standard clinical measure, the composite Unified Huntington’s Disease Rating Scale (cUHDRS). Moreover, the speeded tapping test seemed to perform even better compared to cUHDRS in people early in the disease course of HD (HD-ISS stage 2). This suggests that the HD dMP may enable shorter and smaller trials in the future.
Digital monitoring in HD holds much promise. Currently, the Roche HD dMP is for use in clinical research as a digital health technology tool to determine if it can provide meaningful clinical outcome assessments in the future. The platform is not approved by any regulatory authority as a medical device and is not intended for use in diagnosis, mitigation, treatment, or prevention of disease. Roche is continuing to analyze available data to validate the HD dMP as well as make operational and technical improvements to enhance the user experience with valuable feedback from patients and trials sites.
By combining continuous passive monitoring and active tests, the use of digital monitoring may allow more sensitive measurement of disease progression, which could decrease the required follow-up time and expedite the development of new treatments, leading to earlier and more robust decisions on the efficacy of treatment. By collecting data in the real world, digital monitoring could provide insights into how disease symptoms impact quality of life for people with HD and support efforts to improve those, where possible. Roche and its collaborators are working to see that promise fulfilled soon.