Japanese digital therapy device leader CureApp proves effectiveness in clinical and real-world settings... Expected to become standard treatment
Director Hisashi Miyata (宮田 尚), “While sales of Champix have been halted, distribution of CureApp's SC is experiencing some delays, but CureApp's HT is currently in use at thousands of facilities.”

[관련기사=日 디지털 치료기기 대표 주자 큐어앱 "임상∙리얼월드서 효과 입증…표준 치료될 것"]

[MedigateNews] The digital therapeutics industry has been in a challenging state lately, with leading global player Pear Therapeutics facing bankruptcy and Akili, following suit, shifting its focus from prescription-based to non-prescription digital therapeutic devices.
 
In South Korea, companies are at a crossroads regarding the decision between reimbursable and non-reimbursable options, following the government's July release of health insurance coverage plans. As both reimbursable and non-reimbursable avenues hold their respective advantages and disadvantages, companies are deeply contemplating their choices.
 
What about Japan across the sea in this scenario? Medigate News met with Hisashi Miyata, Chief of Business Development and Operations at CureApp, considered a leading figure in Japan's digital therapeutics industry, to delve into why CureApp entered the field of digital therapeutic devices and its current status. CureApp received insurance coverage for both its nicotine dependence digital therapeutic device, 'CureApp SC,' in 2020 and its hypertension digital therapeutic device, 'CureApp HT,' in 2021.
 
Presently, CureApp faces unexpected challenges such as the suspension of Champix sales affecting the distribution of CureApp SC. However, Director Miyata expressed ambitions based on clinically proven and real-world tested effects, aiming to establish their products as standard treatments. He also hinted at intentions for future entry into the Korean market.
 
Selecting target conditions considering societal impact... Proving clinical effectiveness and reduction in medical expenses.
 
Q: What was the reason for developing DTx for nicotine addiction and hypertension among various conditions?
 
A: Digital therapeutic devices are particularly effective for conditions related to lifestyle habits, dependencies, chronic diseases requiring consistent management like asthma. Kohta Satake (佐竹 晃太), CEO of CureApp, has a background in pulmonary medicine and has observed the effects of smoking on conditions such as lung cancer, COPD, and asthma. In 2007, The Lancet, an international academic journal, highlighted smoking as a major cause of death, resulting in approximately 130,000 fatalities.
 
Satake CEO believed that developing a digital therapeutic device for nicotine addiction, a public health concern, would help the largest number of people and leverage his expertise as a respiratory specialist. Additionally, the choice of hypertension was based on its substantial societal impact upon resolution. This is evident in the actual number of patients, healthcare costs incurred, and future risk assessment.
 
Q: What was emphasized to convince insurance authorities for the application of insurance for both products, which may have faced challenges due to their novelty?
 
A: Ultimately, evidence played a crucial role. For instance, in the case of CureApp HT, a hypertension treatment app, it gained recognition for its efficacy in clinical trials and substantiated its cost-effectiveness in scientific papers. In a multi-center randomized controlled trial, the group using the app showed a 2.4mmHg lower blood pressure in ABPM (24-hour ambulatory blood pressure monitoring) compared to the control group. Moreover, the app-using group had a 4.3mmHg lower morning home blood pressure, where sustained blood pressure control with medication is challenging, demonstrating a clinical significance of reducing the risk of cerebrovascular diseases by 10.7% and heart failure by 54%.
 
Cost-effectiveness analyses conducted by a medical economic assessment firm also indicated a contribution to reducing medical expenses. Lifetime medical expenses with only lifestyle modifications and drug therapy amount to 7,532,718 yen (approx. USD 51,308). Conversely, using CureApp HT alongside lifestyle changes and medication resulted in lifetime medical expenses of 6,936,888 yen (approx. USD 47,249), reducing per-patient lifetime medical expenses by 595,833 yen (approx. USD 4,058) compared to not using CureApp HT.
 
Q: What are the current insurance fees for the two products?
 
A: CureApp SC, a nicotine addiction treatment app, costs around 25,400 yen (approx. USD 173), of which patients bear 30%, approximately 7,620 yen (approx. USD 52). CureApp HT, for hypertension treatment, costs approximately 8,000 yen (approx. USD 55) per month for the initial 6 months, with patients bearing 30%, resulting in around 2,490 yen (approx. USD 17) per month, excluding an additional 420 yen (approx. USD 3) for the initial introduction.
 
Q: What is the process from a doctor's prescription to a patient's actual usage?
 
A: During the initial consultation, the doctor prescribes the digital therapeutic device, issues a code, and sends it to the patient. Upon downloading the app, the patient enters the provided code to activate it. Through the app, patients record treatment progress, their health status, and receive real-time, 24/7 treatment guidance. Doctors can monitor information recorded within the patient's app. This process facilitates patients' behavioral changes and helps in habitualizing these changes through interactions between the doctor and the app.
   CureApp SC requires resumption of Champix sales... CureApp HT prescribed mainly at internal medicine clinics in general
 
Q: How many medical institutions are currently using these products and what are the prescription records like?
 
A: CureApp SC is prescribed alongside Champix for smoking cessation. However, around six months after its launch, Champix faced a suspension due to impurity detection, which also affected our product. At present, it's challenging to disclose the number of medical institutions using our product, as we await the resumption of Champix sales. On the other hand, CureApp HT is currently being used in thousands of medical institutions nationwide.
 
Prescription records are confidential. Considering that digital therapeutic devices might seem unfamiliar to physicians, caution is exercised in prescribing them to patients. Despite this, the process has been relatively smooth. Once prescribed and used by patients, the feedback has been better than anticipated. Both elderly and younger patients have found it useful, showcasing positive effects. By continually providing a positive usage experience for both physicians and patients, it's expected that prescription records will continue to grow.
 
Q: Are there limitations to the specialties that can prescribe these two products? Which larger hospitals or medical institutions show higher prescription rates?
 
A: Prescription isn't limited to specialists. CureApp HT, in particular, is predominantly prescribed in general via internal medicine clinics. For medical institutions with over 200 beds, there are restrictions that limit prescriptions to facilities that have obtained both the government-designated requested treatment-focused medical institutions (which treat patients referred by their primary physicians) and hypertension-certified training hospitals. While it might currently be challenging to prescribe in larger hospitals, there are expectations for wider adoption in the future. CureApp SC can only be prescribed in smoking cessation outpatient clinics.
 
Q: What are the real-world effects observed?
 
A: Analyses of blood pressure data inputted into prescribed treatment apps across the nation’s medical institutions showed that, after 12 weeks, the average systolic blood pressure changes for the entire patient group were -8.8mmHg upon waking and -8.5mmHg before sleep. Notably, for patients aged 65 and above, the recorded blood pressure changes were -11.8mmHg upon waking and -10.1mmHg before sleep. This signifies a demonstrated blood pressure-lowering effect across a wide patient group, including those aged 65 and above, not verified during clinical trials (with the oldest patient being 87 years old).
 
Physicians unfamiliar with DTx, Japanese hypertension society releases 'digital therapeutic device usage guidelines for hypertension
 
Q. What efforts are being made due to the slow diffusion rate of DTx, which is unfamiliar to both doctors and patients?
 
A: For a long time, efforts have been made in academia, such as presenting papers at conferences, garnering significant support within Japan. The Japanese Hypertension Society has already published appropriate guidelines for therapeutic app use. There are plans to continually provide appropriate information to medical professionals. For patients, materials that doctors can use to explain to patients within hospitals are being prepared to address this concern.
 
Q. It's important for patients to continuously use DTx. What efforts are being made in this regard, and what are the related figures?
 
A: Patients have a motivation to treat their illness, and DTx involves doctors monitoring patient app usage while guiding patients through the app. This characteristic has shown higher retention rates compared to typical healthcare apps in clinical trials. The fact that doctors are monitoring encourages patients significantly. Moreover, various efforts are being made to align with the patients' perspectives, such as content that can be easily practiced in daily life and user experience (UX) suitable for elderly users, as over a third of prescribed users are over 60 years old.
 
Q. Continuous updates are necessary for DTx. Are approvals from the regulatory agency required for each update?
 
A: The Japanese PMDA (Pharmaceuticals and Medical Devices Agency) requires partial approval for certain changes that affect efficacy and safety. As factors affecting efficacy and safety vary for each product, it's necessary to review and identify what defines the effectiveness of the medical device program from its development stage. In cases where judgment is difficult, it is recommended to consult the PMDA.
 
For CureApp HT, every year after approval, information about the product's effectiveness is collected and reported to the PMDA to ensure its sustained effectiveness. By annually reporting real clinical data on effectiveness to the PMDA, simple requests for updates can be made to adapt to changes in time and society.
 
The national health insurance system, a Japanese market advantage... Development of DTx for alcohol dependence and non-alcoholic fatty liver disease
 
Q: As a DTx company, what are the advantages and disadvantages of the Japanese market?
A: Japan has stringent regulations on advertising. The inability to directly promote products to patients makes it challenging to raise awareness. However, considering insurance systems and hospital infrastructures, the Japanese market is favorable for the distribution of digital therapeutic devices compared to the United States, which has numerous insurers. Due to differences in insurance systems, the U.S. has limitations on the scope of eligible patients and a complex prescription process, while Japan, with its national health insurance system, allows the entire population to receive digital therapeutic devices through a straightforward process.
 
In Japan, once a device is covered by insurance, it becomes accessible to all citizens. However, in the United States, it requires negotiating with over a thousand private health insurers and state-specific Medicaid programs. Additionally, from a business UX perspective, Japan determines the patient's copay based on age, and hospitals can prescribe access codes for therapeutic apps. In contrast, the U.S. requires individual responses based on the patient's insurance plan and condition, and the process for patients to initiate treatment, even after prescription, involves complexities like visiting a pharmacy
 
Q: Do you have plans for international expansion, including Korea?

A: We have established a subsidiary in the United States to develop products tailored to the local market. There have been discussions about licensing agreements in Korea several times. While negotiations proceeded for two, the terms didn't align, so we couldn't finalize the contracts. However, we find Korea an interesting market due to its strong determination to address smoking cessation and hypertension issues. Although we can develop the app, we lack expertise in the Korean market and hope to collaborate with a company that can facilitate sales.
 
Q: What DTx targeting which conditions are currently under development? Also, any rough plans for their release?

A: We began clinical trials for alcohol dependence from January 2023 and plan to commence trials for NASH (non-alcoholic steatohepatitis) within this year. As for release plans, it's challenging to disclose at this time.
 
Q: How do you foresee the global DTx market, and what role does CureApp play within it?

A: Despite the bankruptcy news from Pear Therapeutics, there are players understanding each country's market structure and witnessing growth in different nations. CureApp is one among them, with room for further expansion. Yet, reaching the point of DTx becoming the standard treatment has a long way to go. Our immediate goal is to expand to the extent Japan has and then take the lead in shaping a world where digital therapeutic devices become the standard treatment.

By Min-sik Park