Global Pharma Giants Bet Big on Digital Biomarkers in 2023: Luca Healthcare Emerges as a Key Innovator

In the New Year of 2023, news spread rapidly that a Takeda executive had joined the advisory board of a Chinese startup.

Ariel Dowling, Global Head of Digital Targets and Digital Measurements at Takeda, officially joined the Scientific Advisory Board of Luca Healthcare (hereinafter referred to as “Luca”) in January.

Founded in June 2021, Luca is one of the first domestic companies dedicated to digital biomarker development. It was established by Dr. Chen Si, the former China Head of Huma, a globally leading digital biomarker company. Its investors include Lightspeed China Partners, Jinding Capital, and Picus Capital. Although Luca may not be widely recognized by the general public, its professional expertise has long been acknowledged by major enterprises both domestically and internationally. Within a year, AstraZeneca, Cambridge Cognition, Shanghai Pharmaceuticals, Thermo Fisher Scientific, Shufang Medical, and PwC all became its strategic partners.

The startup’s ability to rapidly gain recognition from major pharmaceutical and medical device companies is attributable to its core business: the development of digital targets, as well as digital companion products and digital medical products based on these digital targets. As of the end of last year, Luca had successfully developed more than 40 digital targets, with four related products currently undergoing applications for Class II and Class III medical device registration certificates, respectively.

Digital targets remain a relatively new concept in the Chinese market, but abroad, they have become a key focus of research for many pharmaceutical and medical device giants. “Digital target technology holds significant importance for pharmaceutical companies. Currently, major global pharmaceutical companies have established dedicated digital target assessment departments to accelerate their drug development,” said Ariel.

What Are Digital Targets? What Value Do They Offer to Pharmaceutical Companies? What Is the Current Competitive Landscape in the Chinese Market, and What Challenges Exist? VCBeat spoke with Ariel Dowling, aiming to bring a fresh wave of innovation in digital targets to the digital health industry. Next, you will learn:

Basic Concepts:Conducting medical analysis of raw data collected from digital devices to aid in the interpretation, influence, and prediction of disease progression;

Application Scenarios:It can be widely applied to digital drug diagnosis/assessment/prediction, digital companions, medical services, and digital rehabilitation, among others;

Market Stage:The promising market is broad and fragmented, with startups targeting emerging opportunities beginning to appear;

Development Challenges:Cultivating KOLs’ awareness of digital targets, along with the seamless integration of technology and clinical applications, is key.

As a senior digital target developer, ArielShe has infused her passion and aspirations into her professional endeavors. During her doctoral studies at Stanford University, she dedicated herself to applying data measured by wearable sensors, grounded in biomechanics research, to the field of sports medicine.

““I observed that certain athletic habits among athletes often expose them to a higher risk of anterior cruciate ligament (ACL) injuries. This not only causes severe physical pain but, in serious cases, can even lead to loss of athletic ability. However, at the time, there were no effective tools or quantitative methods to identify these high-risk individuals in advance.” Thus, Ariel decided to become the trailblazer.

With a background in mechanical engineering, she developed a wearable inertial sensor system for athletes to measure and analyze knee joint angles and movement patterns during jump training, thereby establishing the maximum knee flexion angle as a digital target for athletic jumping performance.

This was the first digital biomarker Ariel developed in her career. Based on this digital biomarker, she and her team designed a specialized rehabilitation training program that effectively reduced the risk of ACL injuries in athletes, garnering significant attention and citations. Ariel has thus made her mark in the field of digital biomarkers.

Subsequently, Ariel became the designer of digital endpoint algorithms, developing various innovative digital endpoints for numerous small medical device startups to serve the healthcare and clinical trial markets. As she delved deeper into her work, she discovered thatDigital biomarkers and pharmaceutical companies share a natural synergy. “On one hand, pharmaceutical companies possess patient clinical data and clinical data collection scenarios; on the other hand, they are eager to apply digital biomarkers in drug development.”

In 2017, Ariel joined the pharmaceutical industry with the aim of applying her research findings in practice to advance the development of digital targets and feed these insights back into drug R&D. Over the past six years, Ariel has remained active in the sector, steadily increasing industry clients’ acceptance of digital targets, raising broader industry attention, and expanding patient adoption and accessibility. “It is gratifying to see growing opportunities for the application of digital targets in clinical trials and routine medical care,” she said. Perhaps there is no greater fortune than accompanying an industry as it grows.

Throughout her career driven by passion, Ariel has also shared numerous detailed observations and profound insights into the digital therapeutic markets in China and overseas.

Many international publications do not provide a unified definition of digital endpoints, with some conflating digital endpoints and COAs (Clinical outcome evaluation, conflated with (requiring subjective assessment). This has, to some extent, affected the outcomes of communication between medical product developers and regulatory authorities. Digital endpoints are commonly defined within the industry as,Digital medical products that leverage digital health technologies to collect physiological or behavioral data from patients during normal or disease states, and which are validated through evidence-based medicine, thereby achieving the goals of disease diagnosis, assessment, and prediction.

For example, walking is a common physiological behavior. Using digital devices such as smartwatches and GPS sensors, we can measure clinical indicators including walking speed, walking distance, step count, individual gait, and bipedal stability, thereby developing corresponding digital endpoints.

Compared with traditional medical practices such as cellular testing and X-ray imaging, which can only reveal the tip of the iceberg of a disease through intermittently collected fragmentary data, digital endpoints can be measured using wearable, mobile, ingestible, or implantable devices.

This approach enables the acquisition of extensive, continuous disease-related data, providing insights into patients’ health status in out-of-hospital and home settings, as well as verifying whether new drugs or medical devices perform as expected. It offers industry participants, such as digital biomarker companies and pharmaceutical and medical device manufacturers, an important and innovative methodology for uncovering novel disease insights.

Once the behaviors to be measured and the diseases to be assessed have been determined, developers can follow “V3 Framework”to develop and validate digital endpoints—Accuracy Verification, Analytical Validation, and Clinical Validation, this framework represents the expert consensus on digital target development in which Ariel participated.¹。

ArielIt is believed that, given China’s large patient population and the high penetration of mobile phones, digital biomarkers have a natural foundation for growth in China, with greater efficiency in their development and validation, as well as more opportunities for discovering new biomarkers. In terms of application scenarios, digital biomarkers can be widely used in pre-market clinical efficacy assessment of drugs, post-market companion therapy, medical services, and digital therapeutics.

ArielFirst, an analysis was conducted onValue of Digital Endpoints in Pre-Marketing Drug Development: They can serve as clinical endpoints for drugs, enabling a more objective assessment of clinical efficacy.

For example, data show that the Phase III clinical trial success rate for new Alzheimer’s disease drugs is only 25.8%. This is due to the difficulty in diagnosing the disease and the variability in patient symptoms, which prevent the clinical efficacy of new drugs from demonstrating statistical significance during early-stage development. By leveraging objective assessment tools such as the CANTAB test (a tool for early identification of mild cognitive impairment), pharmaceutical companies can more easily recruit suitable patients and predict drug efficacy based on changes in assessment scores, thereby increasing the Phase III clinical trial success rate for new drugs.

Furthermore, digital endpoints exhibit less variability and higher granularity, shortening clinical trial duration and reducing the number of subjects required for enrollment, while still demonstrating the safety and efficacy of the investigational drug.

In this regard, Ariel cited the example of “Moderate-to-Vigorous Physical Activity Index (MVPA),” a digital endpoint recently approved by the FDA for fibrotic interstitial lung disease.². This digital endpoint utilizes smartwatches to assess patients' activity levels, replacing traditional in-hospital cardiopulmonary exercise testing as a clinical endpoint, given that MVPA is more closely correlated with disease progression and offers higher sensitivity.Enables pharmaceutical companies to reduce their Phase III patient recruitment from 300 to 140., significantly improving the efficiency of registration-related clinical trials and reducing clinical costs, while accelerating drug time-to-market.

From the perspective of enhancing therapeutic efficacy, digital endpoints can also serve as digital companion products for pharmaceuticals., improve overall treatment efficacy through AE management, dose adjustment, and medication management.

Digital endpoints can also be widely applied in healthcare services,For instance, by empowering primary care general practitioners to enhance the accuracy and efficiency of disease diagnosis, we enable them to better serve patients through disease screening and diagnosis, remote patient monitoring and health management, as well as prediction and early warning of acute medical events, thereby facilitating the implementation of tiered diagnosis and treatment.

From an intervention perspective, digital endpoints can also serve as assessment endpoints for interventions, thereby forming a closed-loop diagnostic and therapeutic system for digital therapeutics., to realize digitalized and personalized precision medicine.

Currently, participants in the global digital target market are categorized into three groups:

First, pharmaceutical companies: many large multinational pharmaceutical firms have successively established digital medicine departments.Focused on identifying and validating novel digital endpoints for specific diseases within its own drug development pipeline, to create innovative, objective measures of drug efficacy and accelerate drug development.

Disease- and patient-centric nonprofit organizations are also funding research,Develop digital targets for their specific diseases (such as Parkinson’s disease, Alzheimer’s disease, and ALS) to drive the development of innovative therapies.

LucaStartups focused on developing digital targets are also key players in the digital target market.TheyDevelop widely applicable digital endpoints capable of assessing and diagnosing diseases for various digital measurements (such as walking, sleep, respiration, activity, and exercise), and provide services including digital endpoint development and licensing to healthcare and pharmaceutical companies.

Given that pharmaceutical companies’ core business is drug development rather than the development of digital endpoints or devices, they primarily seek collaborative opportunities to maintain their competitiveness in the pharmaceutical sector. Examples include partnering with the aforementioned startups or collaborating with non-profit organizations such as the Digital Medicine Society (DiMe) and the Critical Path Institute (C-Path).

Ariel believes that,It is difficult to say who the largest player is at present, but the impending major trend will be that a few successful companies will consolidate the fragmented market. As the sector matures, there may be a series of mergers and acquisitions. This will reduce fragmentation in the field and, hopefully, enable large companies to collaborate more effectively to jointly drive its development.

China’s digital biomarker market is relatively new, presenting immense potential for rapid expansion. In our analysis of market participants, we identified a contradiction: overseas teams offering digital biomarker algorithms and devices are currently unable to tailor their solutions to the Chinese market due to differing national contexts, while localized teams capable of effectively serving China’s digital biomarker market remain scarce.

The mismatch between supply and demand presents an excellent window of opportunity for Chinese local entrepreneurs to focus on steady growth. And those who canCompanies that seize this opportunity must possess the capability to develop and localize digital biomarkers, as well as the ability to persuade the public to understand, accept, and use devices and applications related to digital biomarkers.

Ariel’s appointment to Luca’s Scientific Advisory Board is a direct testament to her recognition of Luca’s capabilities in these two areas.

“Among the digital biomarker development companies I have engaged with, Luca’s team stands out for its unique composition, bringing together experts in signal processing, algorithm development, medical research, and commercialization. The sound- and neuromotor-based digital biomarkers they are developing are highly innovative and advanced on a global scale, demonstrating superior performance and earning customer recognition. I believe that Luca can introduce many overseas advancements in digital biomarkers to China, while also establishing a foothold in China to develop innovative digital biomarkers with global impact,” said Ariel.

Industries never advance meticulously along the paths people anticipate. More often than not, one crossroads after another emerges, presenting extreme challenges to those within the industry. Digital therapeutics is no exception. As an emerging sector, digital therapeutics currently faces two major challenges:First, persuade key opinion leaders (KOLs), including healthcare professionals and regulatory authorities, to endorse digital endpoints; second, seamlessly integrate the technology into clinical practice without increasing patient burden or complicating workflows.

How Can Healthcare Professionals and Regulatory Agencies Embrace Digital Endpoints? The most intuitive approach is to present them with data metrics from digital products developed based on these endpoints, demonstrating through objective changes in indicators the value of digital endpoints in improving patients’ disease outcomes and quality of life.

“A digital endpoint measuring changes in sleep holds little significance for healthy individuals, but it is profoundly meaningful for those plagued by sleep disorders, thereby carrying substantial implications for healthcare professionals and regulatory authorities.” Ariel explained that major corporations, including Takeda, are promoting the adoption of digital endpoints by continuously investing in foundational research, engaging in extensive in-depth collaborations with startups like Lucan Technologies, and publishing validation data in high-quality peer-reviewed journals to demonstrate the clinical validity, importance, and utility of these digital endpoints within the medical community.

Addressing the second challenge, Ariel explained, “Digital endpoints should not increase the complexity of clinical trials or the burden on patients, as this could reduce patient adherence to using digital devices, ultimately leading to insufficient data collection.” Therefore, when selecting digital devices, companies should prioritize non-invasive, widely adopted devices such as smartphones and smartwatches, and strive to collect data passively from patients.

Furthermore, Ariel discussed the impact of digital endpoints and digital measurements on future healthcare and medical research, as well as the influence of advanced technologies such as wearable devices and artificial intelligence on the widespread adoption of digital endpoints and digital measurements in the healthcare industry. Due to space constraints, this article will not elaborate further on these topics.

Overall, China’s digital target market enjoys favorable conditions for development and significant room for growth. With the competitive landscape still unsettled, any new entrant has the potential to emerge as a dark horse.。

References:

1. Citation of the V3 Framework: Goldsack, J.C., Coravos, A., Bakker, J.P. et al. Verification, analytical validation, and clinical validation (V3): the foundation of determining fit-for-purpose for Biometric Monitoring Technologies (BioMeTs). npj Digit. Med. 3, 55 (2020). https://doi.org/10.1038/s41746-020-0260-4

2: MVPA Endpoints Reduce the Number of Clinical Patient Recruits:https://www.globenewswire.com/news-release/2022/09/27/2523327/0/en/Bellerophon-Announces-FDA-Acceptance-of-Change-to-Ongoing-Phase-3-REBUILD-Study-of-INOpulse-for-Treatment-of-Fibrotic-Interstitial-Lung-Disease.html