Evaluating a Prescription Digital Therapeutic for Pediatric Patients With ADHD

In this interview with First Report Managed Care, Dr Lisa Palko shares an analysis of data from the STARS-Adjunct study, which tested the efficacy of a prescription digital therapeutic among pediatric participants with attention-deficit/hyperactivity disorder (ADHD).

What unmet need inspired your research into children with ADHD?

Akili Therapeutics was founded more than 10 years ago to change the world’s perception of medicine, and we are pioneering the development of cognitive treatments through game-changing technologies. Our approach of leveraging technologies designed to directly target the brain establishes a new category of medicine—medicine that is validated through clinical trials like a drug or medical device but experienced like entertainment. Akili’s platform is powered by proprietary therapeutic engines designed to target cognitive impairment at its source in the brain, informed by decades of research and validated through rigorous clinical programs.

There’s a cognitive crisis in our society, in children and adults, and a lot of people are looking for help. We think the need is vast, and there is tremendous potential for safe and effective treatments that are validated and designed with patients in mind. 

For ADHD, there is a large and growing opportunity for innovative non-drug treatments, specifically to address inattention. Research has shown that individuals aged 6 years and above mainly fall into the inattentive or combined presentation of the disorder, leading to detrimental effects on school performance.  

Most children with ADHD are treated with pharmaceuticals, which lack precision and are designed to treat overt symptoms rather than underlying cognitive impairments. With the lack of options to address inattention specifically, there is a very high unmet need for this population.

Lastly, we often hear from families who are unsatisfied with current treatments and looking for new, non-drug options before putting their kids on stimulants. All these factors led us to explore the data further.

Can you describe your study’s methods and any key findings?

The aim of our exploratory analysis was to evaluate the association between improvements in objective measures of attention and in academic performance.  

We measured attention with the Test of Variables of Attention, Attention Comparison Score (TOVA ACS); arithmetic with the Mathematics Fluency and Calculation Tests (MFaCTs); and reading skills with the Test of Silent Reading Efficiency and Comprehension (TOSREC). The MFaCTs measures arithmetic calculation skills in elementary and secondary school students. The TOSREC is a reliable and valid measure of silent reading efficiency (ie speed and accuracy) and comprehension.

This exploratory analysis was derived from the STARS-Adjunct study, which was an open-label, multisite study in children and adolescents with inattentive or combined type ADHD, stable with or without any ADHD medication. In brief, the study included children aged 8 to 14 years and adolescents with a diagnosis of primarily inattentive or combined type ADHD, confirmed using the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) and the Mini-international Neuropsychiatric Interview for Children and Adolescents (MINI-KID) assessments.  

The study enrolled 206 children and adolescents with ADHD at 15 sites. Participants were instructed to play the AKL-T01 treatment, also known as EndeavorRx, for 4 weeks (baseline to day 28), followed by a 4-week treatment pause and an additional 4-week intervention. Participants completed the TOVA ACS, TOSREC, and MFaCTs at baseline and day 28 as exploratory outcomes. This analysis included both the full cohort (n = 206) and the subgroup of participants who met criteria for attentional impairment (TOVA ACS <-1.8 at baseline; n = 80).

The results suggested that the change in TOVA ACS scores from baseline after 4 weeks of AKL-T01 treatment was positively correlated with change in MFaCTs scores, both in the overall cohort and in the attentional impairment subgroup. We found similar but weaker correlations between change in TOSREC scores in the overall cohort and TOSREC scores in the attentional impairment subgroup. 

How can these findings be used to inform real-world treatment for this patient population?  

We found that changes in attention were positively associated with changes in academic performance (arithmetic and reading scores), providing preliminary evidence of the role attention plays in functional impairments among patients with ADHD in general and academic skills specifically.  

Where do you see the future of care headed as the number of approved digital therapeutics increases?

While digital therapeutics are not yet covered by most insurers, we are seeing that many patients and their families are looking for non-drug treatment options. We believe that safe and effective digital therapeutics will become part of routine clinical care, alongside pharmaceuticals. As the number of approved digital therapeutics increases, there is an opportunity to increase the reach and frequency to patients that may not have otherwise have access to treatments. The future of care within digital therapeutics may help further address health inequities and health disparities.

Is there anything else you would like to add?

On the topic of informing real-world treatment for our patients, we recently launched the EndeavorRx product registry. This aims to get feedback from patients and caregivers using EndeavorRx in real-world settings. We are looking forward to iterating our product based on the feedback we receive, and expanding the real-world evidence base for physicians, payers, and caregivers alike.

We have also shared information about our equitable benefit framework. We are passionate about ensuring that anyone able to benefit from our product not only has equal access, but are able to benefit equally as well. We’re excited to connect with other companies who are inspired by this mission.

About Dr Palko

Lisa Palko, PharmD, is the vice president of medical affairs for Akili, a prescription digital medicine company dedicated to reinventing how medicine is delivered. As a demonstrated leader in medical affairs, she is responsible for leading the overall medical affairs strategy and serves as a trusted scientific advisor in the neuroscience space.  

Dr Palko holds a PharmD from the University of Pittsburgh with a specialization in psychiatry. With almost 2 decades of experience in the pharma industry, she has held various leadership roles within medical affairs, managed markets/HEOR and digital health/medicine.