February 12th, 2019

Welcome to The Future Labs, a Podcast series talking to people building the future, today. We speak to experts around the globe about their role in changing the world for the better.

In this episode, we are exploring The Future of Digital Therapeutics and how we are moving towards a world where patients can be prescribed a digital product (such as a video game) instead of a drug. We are speaking to Eddie Martucci, Founder and CEO of Akili Interactive, a company developing digital neurological treatments in the form of video games, engineered to directly improve cognitive deficits.

What are Digital Therapeutics?

As with many rapidly growing and innovative areas in technology, the vocabulary around “Digital Therapeutics” and “Digital Medicine” is still evolving, but, at its core, is the idea that digital solutions (i.e., software and apps) can be used as part of the medical treatment and/or management of specific diseases and conditions.

Eddie summarises how Akili views the space: “We see digital medicine as meaning digital or software platforms that are having a direct impact in patients’ lives with clinical outcomes, so when we say digital therapeutics we’re talking about software that can somehow aid in the clinical management or treatment process, that is still a relatively wide net as you can imagine so there’s a few dozen companies that are doing different versions of that”.

Digital Therapeutics can be considered to be a subgroup within “Digital Health”, which comprises all digital solutions developed to help improve health, typically through behavioral modification or treatment management. The key distinction between Digital Therapeutics and other approaches is that they are developed to have a measurable and clinically-validated impact on a specific condition supported by peer-reviewed data. This is in stark contrast with direct to consumer products thatsimply aim to improve overall “wellness” (e.g., weight loss, activity tracking). Digital Therapeutics require regulation via the FDA (in the USA) are comparable to more traditional therapeutics (e.g., pills, tablets) that physicians are already accustomed to prescribing.

“We see digital medicine as meaning digital or software platforms that are having a direct impact in patients’ lives with clinical outcomes, so when we say digital therapeutics we’re talking about software that can somehow aid in the clinical management or treatment process, that is still a relatively wide net as you can imagine so there’s a few dozen companies that are doing different versions of that” - Eddie

Such therapeutics are mostly focused on the management or treatment of specific chronic conditions through improved monitoring, management, and behavioral optimization. There are two major categories within this definition of Digital Therapeutics: 1. Augmenting / Companion Solutions, which are intended to complement and enhance the effectiveness of existing therapies. These typically focus on optimising patient behavior associated with a specific medication, either through improving dose selection and frequency or by improving their “compliance” with a companion drug (i.e., ensuring they don’t forget or skip doses). Examples of this approach include:
  • Propeller Health has developed an integrated device and software solution that combines with inhalers such as GSK’s Ellipta inhaler (used for asthma and chronic obstructive pulmonary disorder) to improve patient behavior and compliance with their treatment.
  • Proteus Digital Health has developed a “digital pill” technology that comprises a sensor embedded in a pill that signals to a wearable device and a patient’s mobile phone to confirm that the pill has been taken correctly. The first medication incorporating this technology was approved by FDA in 2017 – Otsuka’s Abilify Mycite / aripiprazole tablets for schizophrenia and bipolar disorder.
2. Replacement Solutions, which are intended to be standalone therapies that can be prescribed for a specific condition in the same way a drug would be. Importantly, the therapeutic is not an “add-on” or “supporting tool” for a drug, instead, these products have intrinsic clinically validated value to patients
  • Pear Therapeutics has launched the first FDA-approved Digital Therapeutic with Sandoz (Novartis) – “reSET-O” is a 12-week cognitive behavioral therapy for the treatment of Opioid use disorder. This product supports existing opioid replacement therapy and is given in addition to traditional medical support.

Digital therapeutics have the potential to both work alongside traditional medicine as well as to become a brand new class of therapies in their own right . Eddie makes it clear that Akili fits squarely in this second category: I think where Akili is a little on the edge (and had a big bold vision a few years ago) was the belief that software could in and of itself could be the treatment, so when we say digital therapeutics that are made by Akili we’re talking about software that in and of itself could be prescribed by a doctor and directly treat a disease even without anything else, just standalone

Digital therapeutics have the potential to both work alongside traditional medicine as well as to become a brand new class of therapies in their own right. - The Future Labs

Where did the idea for Akili come from?

Akili was founded in 2011, around the time many large pharmaceutical companies such as Novartis, Pfizer, GSK and AstraZeneca were announcing cuts to their neuroscience and neuropsychiatry research and development efforts. This occurred against a backdrop of increasing clinical need for therapies, leaving patients with fewer prospects on the horizon. Eddie recalls that this was occurring just as consumer technology such as smartphones were becoming omnipresent and providing a new platform for interacting with potential patients:

So that was right around the time when you would see people on trains using Apps for everything, playing games, communication, managing their life in other ways, their finances… we now have this platform that is obviously directly interacting with a patient all the time

This also coincided with advances in scientists’ understanding of how to stimulate the brain in predictable ways through the use of sensory methodology, including via video games. Eddie and his co-founders were inspired to take advantage of the pharma exodus from neuroscience, the rapid spread of a platform that could be used to engage patients and the concurrent improvement in our understanding of the human brain to create a digital therapeutic approach for neurological diseases.

Early on they discussed the different approaches they could pursue and concluded that they could “
do something sort of minimal there, something simple like let’s connect the patient with a mental health service … or we could go crazy and say let’s put all three of those things together and try to find new technology that stimulates the brain in a new way that could look and feel like a game in your pocket, and add to that let’s try to get it through FDA so that doctors could prescribe it to help people

What is Akili doing?

Akili has positioned itself as a digital therapeutics player with a portfolio-based approach rather than a single technology approach. This is driven by a strong conviction in the value of digital therapeutics over the next 5-10 years and a desire to be one of the major companies in this space. Eddie sees Akili as a pioneer that can own the space through offering a number of different digital therapies all united through their focus on “the best in the world technologies that can stimulate really specific neural circuitry that’s important for different diseases through sensory and motor stimulation”. This means that they are looking to find and develop a platform technology that has applications across multiple diseases.

Although Akili has several different technologies in development, the only publically disclosed program is their “Selective Stimulus Management” technology, which was licensed from the University of California, San Francisco (UCSF) following years of research. This is a specific algorithm platform that combines sensory decisions with motor challenges in a specific way that activates the middle prefrontal cortex, the region of the brain responsible for maintaining attention function and inhibitory control, sometimes known as the “executive control center” of the brain. The idea is that by selectively stimulating this region one could improve attention control.

Akili has incorporated this technology into an interactive video game called “Project Evo” (AKA “EVO” or “NeuroRacer”). Project Evo was developed to look and feel like a high-end video game that has intrinsic entertainment value in its own right. Patients playing the game are bombarded with visual and audio stimuli determined by the adaptive algorithm, which is designed to find the “sweet spot” of difficulty for each user to stimulate the prefrontal cortex and to strengthen the neural networks there. With this, Akili demonstrated that playing the game had a measurable and statistically significant impact on attention control in children with attention disorders. To date they have collected data showing this effect in children with a range of attention disorders including: hyperactive disorder (ADHD) (Davis et al., 2018), sensory processing dysfunction (SPD) (Anguera et al., 2017), ADHD and autism spectrum disorder (ASD) (Anguera et al., 2016; Yerys et al., 2018). Further, Project Evo has been tested in people with late-life depression and found to improve cognitive control deficits (Anguera et al., 2017b).

Conducting multiple clinical studies has been an expensive endeavour for Akili, but Eddie believes that it was necessary to pursue FDA approval as a therapy and be used by doctors as such. Akili has been active in speaking to the FDA, starting in 2014-15, and Eddie notes that FDA has been very receptive to leading-edge ideas and that they have invested in bringing in expertise and providing support around trial design.

Akili is looking to develop therapies for other neurological conditions beyond attention disorders and Eddie notes that they have an interest in addressing specific needs in “depression … multiple sclerosis, Parkinson’s, lupus and a few other early conditions where we’re looking at being able to have a direct treatment for different types of cognitive dysfunction that’s limiting someone in their daily life”.

“So that was right around the time when you would see people on trains using Apps for everything, playing games, communication, managing their life in other ways, their finances… we now have this platform that is obviously directly interacting with a patient all the time” - Eddie

What does the Akili team look like?

Prior to co-founding Akili, Eddie worked at PureTech, a healthcare investor based in Boston, where he focused on traditional biopharma (i.e., drug development) opportunities, drawing on his Ph.D. in Biochemistry and Biophysics at Yale. Eddie notes that although Akili is developing software, a lot of the founders and executive team “comes from a more traditional scientific background and even a traditional drug or pharmaceutical background”. Eddie sees the drug development experience his team brings to the table as valuable, not least when it comes to thinking about how to develop their product through rigorous clinical testing. This is in contrast to the other approaches in development back in 2010 where “you were seeing a lot of things on the consumer market that were going in a very non-scientific path and delivering things to consumers that were totally unvalidated”.

Eddie describes the spectrum of people at Akili as “crazy and diverse, and probably the most diverse group of people I’ve ever worked with”. The team is comprised of people with experience developing drugs, devices, finance software, games, people who have run clinical trials as well as artists and user experience experts “who sit with children and adults and try to figure out which buttons are easiest to use”. This diversity has allowed Akili to think creatively about treating tough neuropsychiatric diseases and he describes the variety in experience as “one of the secret sauces of Akili”.

Although interest in digital solutions for healthcare has increased hugely in recent years, Eddie notes that many companies have expertise in either technology or in healthcare and try to move into the other space. Akili’s multidisciplinary team may give them an advantage in this space, but it also brings with it challenges around managing teams of people with very different backgrounds. In some cases, there may be a lack of shared vocabulary that hinders communication or simply differences in base levels of understanding around how certain processes work.

How will Akili’s technology be used in the real world?

Akili could see commercial launch of Project Evo as early as late 2019, and they have conducted significant research into how patients, doctors, and payers (e.g., insurers) feel about the product. Physicians that treat behavioral and cognitive disorders may be more open-minded about such novel therapies than those in other specialties, in part because they have a long experience of limited success with traditional therapies such as drugs. Eddie notes that some patients are managed well with existing drugs but “a lot of patients are not able to tolerate the medication, they have a lot of side effects, also a lot of patients and families just opt not to take pills for their conditions”. Physicians will need to see evidence that the technology works to get comfortable using Akili’s technology, and data collected in clinical studies should address this. Eddie has found that once physicians review Akili’s data they are quite receptive to the idea, albeit with a number of follow up questions such as “am I going to have to tech support for this person?”.

Another consideration that patients and families need to consider is that using a digital therapeutic such as Project Evo requires more engagement and time than simply taking medication. Patients in Akili’s Phase 3 study, which finished in December 2018, played for 20 minutes per day, 5 days a week, for a month. Efficacy was measured at one month and showed a clear benefit, but the effect is not immediate and does require longer-term commitment to the therapy. Eddie thinks digital therapeutics companies that will be most successful in this space “will not just get the medicine part right, but they will get the user experience part right, because you’re going to need incredible user experience to have patients using this for extended periods of time”.

“I get asked this a lot … “I’m not sure” is the honest answer, it’s like asking “How important are department stores going to be for the growth of the online retail industry?” 15 years ago”. - Eddie

What role are traditional pharmaceutical companies playing in digital therapeutics?

Pharma companies have demonstrated significant interest in digital therapeutics, in some cases have partnered with developers (e.g., Novartis / Sandoz with Pear Therapeutics) as well as building some internal capabilities in this space. Eddie believes it is too early to answer “What role Pharma will play in bringing digital therapeutics to patients?” “I get asked this a lot … I’m not sure” is the honest answer, it’s like asking “How important are department stores going to be for the growth of the online retail industry?” 15 years ago”.

What’s the Future of Digital Therapeutics?

Eddie has high hopes for the role of such therapies in medicine in 20 years time: “It’s going to sound trite but I honestly think in 20 years we’re going to look back and say “remember that silly time when we only treated people with drugs?” … I think pharmacology will still be a pillar [of medicine], but I think this could be a new pillar in medicine and it will feel like this is how it’s always been”.

 

What about you? What are your thoughts on this new space?