At the end of June, the frontrunner in the race to develop and commercialise a drug for non-alcoholic steatohepatitis (NASH), a common, lifestyle-related liver disease with no approved therapies, Intercept’s obeticholic acid (OCA) was rejected by the US Food and Drug Administration (FDA).
In a complete response letter regarding Intercept’s new drug application (NDA) for accelerated approval, the FDA stated that the predicted benefit of OCA based on histopathologic endpoints was too uncertain and did not outweigh the potential risks of the drug. The FDA called on Intercept to submit additional efficacy and safety data from its ongoing Phase III REGENERATE study of OCA.
This marks a huge setback for NASH patients as Intercept’s NDA for OCA was the first for this indication. However, unfortunately, this is not the only recent bad news in the field of NASH. Two other companies, Gilead and Genfit, had NASH drugs fail in late stage clinical trials.
At the end of 2019, Gilead announced its two therapies – firsocostat and cilofexor – failed in a Phase II trial both alone and in combination to reduce scarring in patients with advanced fibrosis without worsening of NASH.
This comes within a year of Gilead’s Phase III failure of selonsertib; the drug was not superior to placebo in improving fibrosis in NASH patients. While Genfit’s elafibranor failed to achieve its primary or second endpoints in the Phase III RESOLVE-IT study; this drug has been touted as potentially the second in line – after Intercept’s OCA – to receive FDA approval.
The lack of any treatments leaves patients reliant purely on making drastic lifestyle and dietary changes with limited support or risk requiring a liver transplant as the disease progresses into more severe conditions, such as cirrhosis, liver failure and liver cancer. There is an urgent need for something to change for these patients, particularly as the incidence of NASH is on the rise.
Enter CureApp and digital therapeutics
Japanese health technology company CureApp wants to transform this dismal outlook for NASH patients using digital therapeutics. It was named as one of the World Economic Forum (WEF)’s 2020 technology pioneers for its work on using the power of digital technology to improve lifestyle interventions.
CureApp CEO and co-founder Kohta Satake explains that the company’s digital therapeutic app aims to overcome the challenges NASH patients face in making lifestyles changes and slowing liver disease progression.
“The current treatment guideline for NASH recommends 7% weight loss from lifestyle changes as the sole treatment,” Satake notes. “However, it takes a long period of time and effort for a patient to correct one’s lifestyle habits, which is difficult to achieve by themselves with minimal or no external support.”
This is where CureApp’s NASH digital therapeutic comes in. It aims to provide real-time, personalized lifestyle management guidance for each patient.
This support is based on “daily inputs from doctors and patients, which include individual progress and status updates, [as well as] their symptoms”. Satake explains that CureApp’s algorithm is used to adjust the treatment guidance to each individual patient and is further supported by specialist medical knowledge about this disease area.
Importantly, CureApp believes this means that the NASH patients can properly supported in their treatment all the time, rather than having feeling unsupported between appointments with physicians. Continuous treatment is seen to be the best way to achieve changes in behaviour around lifestyle and diet.
Therefore, the idea is a remote, digital therapeutic approach that can “prevent the transition to a more severe liver disease by supporting patients at home that could not have intervened with the current treatment”, explains Satake. ““We believe our NASH solution can be the primary solution to the NASH treatment.”
Need for clinically approved apps
To develop the NASH digital therapeutic and its underlying algorithms, CureApp is working with the two professors from the University of Tokyo – Kazuhiko Koike and Masaya Sato.
The partnership is currently undertaking a multi-centre Phase II trial; the study began in April 2018. Satake notes that Koike’s expertise in the NASH field has been instrumental to the development of the digital therapeutics’ proprietary algorithms.
For Satake, it is crucial that CureApp’s personalised digital therapeutics are backed by strong evidence. He sees this as the main differentiator of CureApp’s products from other wellness or healthcare apps on the market for various conditions.
In addition to being supported by clinical studies, Satake explains CureApp’s digital therapeutics “go through rigorous development and validation processes to meet regulatory requirements so they can be used in clinical settings”. Concrete, clinical evidence is also essential to these products being reimbursed by public healthcare systems.
This also allows CureApp to gain the trust of healthcare providers when they are prescribing these apps. “Firm evidence has been the basis of medical practice for a long time, and thus physicians who practice medicine put importance on it”, states Satake.
Beyond NASH: apps for smoking cessation and hypertension
CureApp is not only working on digital therapeutics for NASH. Satake noted in a statement about the WEF announcement: “With the evolution of technology, it is becoming clear that lifestyle interventions with mobile apps produce remarkable therapeutic effects for various disease groups that were difficult to approach with traditional interventions.”
To this end, CureApp is currently developing apps for two other lifestyle-related conditions the pharmaceutical industry has struggled to resolve: smoking cessation and hypertension.
“Smoking is a serious cause of death and a risk factor for various illnesses,” notes Satake. “We believe that tackling smoking cessation issues has great value in public health.” However, like with NASH, there is insufficient support for patients, particularly around treating “the psychological dependence, which is essential for successful smoking cessation.”
CureApp has completed a clinical trial with 600 patients for its smoking cessation digital therapeutic, which has been developed in collaboration with Keio University’s School of Medicine. The app is linked with a Carbon Monoxide monitor to help patients track their progress.
The company recently completed a Phase III study for this product and is now engaging in conversations with Japanese regulators about approval of the product. Satake is expecting the marketing authorisation to come through in the coming months.
The hope is that this would be followed by insurance reimbursement in Japan by the end of the year, which would make CureApp’s product the “first digital therapeutic case to reimbursed by the national medical insurance system in Japan.”
CureApp’s hypertension product also entered Phase III trials at the end of 2019. This digital therapeutic is being jointly developed with Jichi Medical University.
Similarly, to both NASH and smoking cessation, “Lifestyle improvement is essential for prevention and treatment [for hypertension]”, but meaningful change is hard for individuals to manage without proper support, Satake explains. “We believe that digital intervention for hypertension can help patients and reduce overall medical expenditure.”
Satake notes that CureApp is planning to expand its suite of lifestyle digital therapeutics over the coming years. Its next focus will be alcohol addiction, which it has been studying with the National Hospital Organization’s Kurihama Alcohol Center.