In a new era of Alzheimer’s disease research, the emergence of blockbuster therapies like Eli Lilly’s Kisunla (donanemab) and Eisai and Biogen’s Leqembi (lecanemab) offer renewed hope to patients and researchers.
Despite their promise, these therapies have faced significant regulatory and access challenges. In July, the European Medicines Agency (EMA) said Leqembi’s efficacy was “not large enough” to outweigh its safety risks, and in October, the UK’s National Institute for Health and Care Excellence (NICE) recommended against the widespread use of Kisunla.
These setbacks highlight the complex path forward for proving effectiveness with innovative therapies, as researchers and trial sponsors find ways to balance clinical rigor with the unique needs of a patient population experiencing cognitive decline.
Unlike decentralised studies in other therapeutic areas, factors like cognitive decline, which is inherent to Alzheimer’s disease, impact patient recruitment and engagement and the effective use of digital health technologies like wearables, sensors, and mobile apps.
A Clinical Trials Arena’s exclusive analysis reveals that the proportion of decentralised trial initiations rose sharply after 2018, peaking in 2021, but has since experienced a drop. This downward trend has been more extreme in Alzheimer’s DCTs. By 2023, only 7.09% of all Alzheimer’s trials were being conducted as decentralised studies, representing a sharp decrease from the peak seen in 2021,
When designing trials for Alzheimer’s, it is essential to ensure that studies are as convenient as possible for both patients and their caregivers whilst balancing adequate study of the candidate, says Sandi See Tai, chief development officer at New-York based biotech Lexeo Therapeutics.
As per an exclusive analysis by Clinical Trials Arena, Eli Lilly is at the forefront of using DCTs in Alzheimer’s research, with Kisunla leading as the drug most frequently investigated in Alzheimer’s DCTs. With GlobalData forecasts estimating billions in potential revenue for both Kisunla and Leqembi, the drive to bring these treatments to patients remains strong – but so do the challenges of ensuring safe, accessible trial processes.
Balancing robust data collection with patient convenience
As clinical trials for Alzheimer’s therapies evolve, finding a balance between collecting comprehensive, high-quality data and maintaining patient convenience is crucial, especially for long-term studies. This challenge is particularly evident in the case of gene therapies, such as Lexeo’s AAVrh10-based gene therapy LX1001. With a one-time dose followed by five years of follow up, ensuring that patients stay engaged over the long term requires thoughtful integration of decentralised trial elements.
See Tai says the company has tried to ease the burden on patients and their caregivers, by providing the option for virtual visits. Certain visits can be conducted remotely, and logistical support is offered to facilitate blood sampling with vendors, reducing the need for patients to travel.
However, for more invasive procedures like MRIs, PET scans, and lumbar punctures – key for understanding treatment effects – remote alternatives are not feasible. “You have to get the data you need to understand the treatment effect,” See Tai adds.
This is a challenge that is particularly prominent in Alzheimer’s trials with monoclonal antibodies like Kisunla and Leqembi, which come with the risk of amyloid-related imaging abnormalities (ARIAs). Symptomatic ARIAs can lead to headaches, confusion, or more severe neurological symptoms, requiring dose adjustments or pauses that disrupt treatment, and a warning for ARIAs is included on the labels for both drugs.
Shobha Dhadda, Eisai’s chief clinical science & operations officer explains that the company has been incorporating decentralised elements into its Alzheimer’s trials to gain granular insights into disease progression and patient responses. However, “ensuring data integrity, dealing with technology literacy among older populations, and addressing privacy concerns for sensitive patient data,” are all important, she says.
For Alzheimer’s trials, the challenge extends beyond patient convenience to include the needs of family members who play a crucial role in supporting patients. “When we think about the trials, it’s not just about the patient, but also about facilitating the caregiver,” See Thai explains. “It’s about minimising the number of visits and procedures and determining what’s truly needed to make it feasible for patients and their families.”
This patient-centric approach is key to enhancing trial retention and ensuring that Alzheimer’s treatments undergo the rigorous testing required for long-term success. “You really want to make it as convenient as possible so that you could collect the most information,” explains See Thai.
How will the tech boom impact Alzheimer’s trials?
The rapid growth of digital health technologies and the rise of artificial intelligence (AI) have revolutionised the landscape of clinical trials and scientific research. According to Sarah Lott, research lead at the Digital Medicine Society (DiME), a global non-profit for the digital medicine community, the opportunities for these technologies in Alzheimer’s trials is vast.
Lott says digital tools like wearables and sensors present the opportunity to measure a wide range of health metrics like physical activity, sleep, cognition, mood, and speech. These tools provide a more comprehensive and dynamic picture of a patient’s health over time. “The neat thing about digital health technologies is we can measure continuously or repeatedly, and suddenly we’re really understanding how that person is doing,” Lott explains.
As per Clinical Trials Arena's analysis, telemedicine is the leading virtual tool used in Alzheimer’s DCTs. It is utilised in 55.7% of all Alzheimer’s DCTs, followed by remote monitoring by a sensor, device or tracker, digital data collection, and decentralisation to home alternatives.
In addition to improving data quality, digital health technologies have the potential to improve patient recruitment. By enabling remote monitoring, these tools help overcome some of the logistical barriers that have historically limited access to clinical trials, opening them up to rural and hard-to-reach communities. “We can now democratise access to clinical trials in a way we really couldn’t before,” says Lott.
Dhadda says Eisai has been leveraging telemedicine and wearable devices for the real-time monitoring of cognitive function and patient safety. “The use of digital cognitive testing platforms allows for standardised and scalable assessment, while remote consultations reduce the need for frequent on-site visits. These elements not only reduce patient burden but also enhance recruitment by increasing accessibility,” said Dhadda.
Technological advancements also allow for more nuanced data collection, said Dhadda. As per Clinical Trials Arena’s analysis, safety and efficacy are the two endpoints investigated most in Alzheimer’s DCTs.
Dhadda explained that as technology gets more sophisticated, Quality of Life (QoL) as an endpoint is becoming increasingly important. “Eisai prioritizes QoL metrics to ensure a holistic understanding of treatment impact. For instance, the inclusion of wearables and digital platforms in trials provides dynamic QoL insights, facilitating a more comprehensive assessment of therapies’ effectiveness from both medical and patient perspectives,” she said.
Lott added that although QoL is being looked at more, “we are still not at the point where they are being used as primary endpoints.”
Tailoring digital tools to the needs of patients
The adoption of digital tools is not without its challenges. Ensuring that these tools are user friendly is critical for successful integration into Alzheimer’s clinical trials, emphasised Lott. “Are these technologies we’re asking folks to use…going to be a barrier? Are they going to be uncomfortable?” Lott asks.
DiME has seen an increase in ambient technologies – non-wearable devices such as cameras, microphones, or pressure mats embedded in beds or environments that collect data without burdening the patient. These technologies allow for the collection of meaningful data in a thoughtful manner while minimising discomfort and disruption to the patient’s daily life.
“We are in this space where we have so many technologies that can do so much that we have no excuse not to find what's the right sensor or technology for this population that will serve them in a way that doesn't also burden them.” Lott concludes.
