Adherence Issues Add Weight To Digital Trials Push
Technology advancement has brought a wave of change in healthcare, with an increasing number of key pharma players now recognizing the potential of digital – particularly in clinical trials.
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One day in the future, clinical studies may routinely be carried out in the virtual world, with patients mostly staying put at home instead of traveling to trial sites. For now, sponsors are experimenting with new models for drug development and taking it one step at a time.
Otsuka plans a slow, measured launch of Abilify MyCite, developed with Proteus Health. The product includes an ingested sensor that sends a signal to a wearable patch and an app that tracks ingestion, activity and mood to potentially improve management of psychiatric care.
"In the computer industry 20/25 years ago, computers were designed for customers just like their makers. You were a computer worker, a hobbyist or knew someone who was. Computers were sold based on what speed their clocks ran at or how big a hard disk drive was – things that most people didn't really care about. That changed with the smart phone, when designers started to work on products that were meaningful to everyone, including people who didn't like computers.
"I think we need to get there with healthcare (and we are going to get there) in the same way.
"Right now drugs are designed by doctors for doctors and if a patient is in hospital that works well. That is the story of 20th century medicine, you have doctors and nurses who give you your medicines, measure effect and adjust the therapy. If everything goes according to plan, you can go home. With chronic disease, we have no user interface for a person who has to fit this therapy into their daily lives. It all has to work for the doctor and patient. We need to build in features that work for regular people in their daily lives and I think that is the biggest opportunity right now to affect world health for the better." - George Savage, co-founder and chief medical officer of Proteus Digital Health.
Founded in 2001 by CEO Andrew Thompson, Mark J. Zdeblick and George Savage himself, Proteus Digital Health is a company aiming to merge the digital world with traditional medicine. Back in 2004, the company raised capital that enabled it to hire employees with the aim of building information into medicine. Proteus has created an ingestible sensor that can be taken with medication to assess a patient's adherence and reaction to a drug. The company is working towards building these sensors directly into prescribed pharmaceuticals with the hope of not only enabling patients to get a better idea of their health, based on their decisions and patterns, but also giving physicians and health systems the opportunity to manage risks more effectively. It is exploring the transplant area with partner Novartis and in Sept. 2015 filed for US approval of a digital drug combination of Proteus' ingestible sensor and partner Otsuka Pharmaceutical's Abilify (aripiprazole). Abilify is an atypical antipsychotic for schizophrenia and other serious mental illness, an area which FDA suggested the digital health company begin in. Savage spoke to Scrip's Lubna Ahmed about the future of medicine, a future which Proteus is determined to have a hand in shaping.
Lubna Ahmed: What is the idea behind Proteus?
George Savage: We realized that implantable devices, like pacemakers for the heart, were becoming more sophisticated. They went from being timed devices to sophisticated computers with memory allowing physicians to observe a patient's heart activity, what the device had done to help and then tune the device for that individual. With the rise of cellular mobile technology, there is an opportunity to do something like this for people around the world who have to take medicines, particularly on a chronic basis, where it is unknown exactly how well they're working, how well they're being taken or whether it's the right dose.
This is the most significant opportunity to affect public healthcare around the world ever. If you look at the 2003 World Health Organization (WHO) report, the estimated rate of adherence to medicine around the world (without regard to culture or diagnosis) averages 50% or less. This is a global problem. No matter what I come up with, a better cure or treatment, no matter how brilliant my development team or clinical work is, half of everyone that we might help is completely out of the equation from the get-go. If you could deliver an information platform, which is what we're aiming to do to get at this problem, you have an opportunity to do something about that.
LA: How does Proteus' technology work?
GS: This technology has potential to deliver an accurate picture of how you are taking medication and how your body is responding and therefore ensure you're on the right dose or medicine. What distinguishes Proteus is the ingestible sensor, a microscale device, which is the world's smallest medical device, composed of ingredients in your diet. This device can be incorporated into a placebo pill, which is how it's approved as a medical device right now, and also directly into pharmaceuticals, which is the subject of further FDA approvals: our partner Otsuka has a New Drug Application (NDA) on file on one such medicine now.
Sensors are programmed with a unique ID code and either side of this 'grain of sand' are essential minerals. On one side is a thin film of magnesium and the other a thin film of copper – when two dissimilar metals get wet, they form a battery. These films are sized so that they power the chip for a brief period of time, allowing it to send signals only within the body (not anything that can be picked up beyond the skin) to a digital band aid worn on the torso. This ingestible sensor monitors the pills being taken and records the body's angle, activity and heart rate and the temperature of the device. When near a phone, it will be updated with all the information since the last time the patient was nearby and this can be sent to a personal health record that can be shared with doctor.
For patients it can be difficult to interpret what is going on. They only have a few minutes with the doctor, who can be busy, and it can be stressful in between as it's hard for most people to figure out how they're doing and how to get better. This technology will provide healthcare teams and patients the ability to know what is going on.
Basis of Proteus' technology: The band aid and microscale sensor (Source: Proteus)
LA: What Proteus is doing is different. Do you have any competitors?
GS: We really don't, not in terms of the ingestible sensor arena, and if you're talking about digitizing drugs we're the only game in town. Other digital companies are doing interesting things like those in precision medicine trying to analyse the genome and predict things, we view that as complementary. The real competition we face is the existing way of doing things. It's sort of provider and payer: even if everyone agrees we're the future there is this notion of 'just not yet!' From that perspective we link arms with our brethren in the digital space to point out that they may be part of the solution too – this isn't just Proteus and not the other guys – it's embracing the mobile platform to move forward to a better value healthcare model.
LA: How would regulatory processes work with this?
GS: Currently the commercial route that can be used is through co-ingestion: the medical device can be taken separately alongside the medicine being prescribed and used to get data, and the pharmacist may compound the medicines together with the sensor tablets within a capsule, creating a unified dosage form on a named patient basis. Four years ago we reached an agreement with the FDA and EMA for NDA approval of already established medicines, which is that provided we are simply merging labels, taking existing medicines and adding the device, there is no need to re-demonstrate safety or effectiveness of either component. Review at the regulatory agency will focus on the CMC concerns, for example whether the new formulation is stable when the chip is compressed inside; whether the drug goes bad; whether the device works; as well as basic usability: can the target population use the product and interpret the results on their phones?
This technology will provide healthcare teams and patients the ability to know what is going on (Source: Proteus)
LA: Serious mental illness is one area, are there any other areas Proteus is interested in?
Opportunities are limitless, actually. We have investigator-initiated studies in various areas but are focused on the high-value medicine and cardiometabolic arena, referred to as comorbid hypertension, which is the combination of high blood pressure, high blood sugar and often high lipid levels. The advantage for Proteus is that drugs used to treat these conditions are primarily generic, meaning we can initiate the process with FDA of digitizing those therapies directly.
High-value medicines are drugs that are either very expensive themselves or represent a gateway to expensive therapy. For example the new hepatitis C agents, which are expensive but where adherence is important, or antiretroviral drugs. We have some investigators receiving grants to study the technology with antiretrovirals for the prevention of HIV transmission. We also have a trial underway in using technology to try and replace directly observed therapy with wireless therapy to help in tuberculosis management.
LA: How do pharma companies react to Proteus?
It varies. Pro-side people understand that everything is becoming digital. Proteus' thesis is it's guaranteed to happen to healthcare. Whether you think Proteus is part of that answer – I hope and believe we are – pharma companies will need to accept that this is going to happen somehow so they need to be part of it. Where there's a range of reaction is the potential for new business models. In the long run this maybe a substantial opportunity for the industry, although it is difficult in the short term. Companies could have a more sustainable business model by moving to value. If they have digital technology they can see how well products are working, and by partnering with a health system they can offer a more sustainable, if maybe a more complicated and potentially risky, endeavor. Instead of charging for chemicals, they could focus on and participate in how much value is being added for the patient.
The advantage in this data-driven analytics outcomes model for pharma companies is their business model won't be as dependent on composition of matter patents.
LA: What is Proteus planning to do next?
GS: We have our own trials underway in cardiometabolic disease and you will be seeing some data in the New Year that show patients are not only able to treat themselves to goal but they also have a high favorability rating of the system. These are patients who are typically at risk of diabetes and hypertension. We are also moving forward with a Proteus-sponsored drug application with FDA for taking today's established medicine and adding in sensors to treat cardiometabolic issues. We're also rolling this out with some health systems, focusing on the US with existing device-related approaches, where a patient will co-ingest the device with the drug of interest that either the pharmacist has compounded or individually.