Besides essentially being epidemics and costing increasingly exorbitant amounts, what do many cardiometabolic diseases have in common? They’re driven mainly by individual behavior. Between 70% and 90% of cases with these highly prevalent and interrelated set of conditions are directly attributed to modifiable behaviors.
Although there is promise in some therapeutic candidates that could be part of a program to reduce risk for cardiometabolic diseases—such as a gene-editing treatment from Verve Therapeutics that lowers bad cholesterol (VERVE-101) and an FDA-cleared biomimicry-based weight management aid by Gelesis (Plenity)—there isn’t so far a therapeutic to fix the root causes for this interrelated set of diseases, to fix poor diet, sedentary activity, smoking, excess alcohol intake, or the combination thereof. Nevertheless, to prevent the likes of cardiovascular diseases, such as coronary heart disease (CHD), stroke, and hypertension, as well as metabolic diseases, such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD), what’s needed is behavior change.
Better Therapeutics (NASDAQ: BTTX) is a prescription digital therapeutics company developing a novel form of cognitive behavioral therapy (CBT) to address the root causes of cardiometabolic diseases while lowering healthcare costs. The CBT delivered by the company’s prescription digital therapeutics is designed to enable changes in the brain’s neural pathways in order to effect lasting changes in behavior. The company has developed a proprietary platform for developing FDA-regulated, software-based solutions for type 2 diabetes, heart disease, and other conditions. Better Therapeutics’ clinically validated mobile applications are intended to be prescribed by physicians and reimbursed like traditional medicines.
GEN Edge met with co-founder and CEO Kevin Appelbaum to get up to speed with how being a digital prescription therapeutics company differs from traditional pharma and bioscience companies.
GEN Edge: What drove the idea behind Better Therapeutics?
Appelbaum: We’re about six-and-a-half years old and started based on several observations. First, the diseases that affect the most people and consume the most healthcare resources are largely caused by our own behaviors. Second, we currently treat those diseases, relying almost exclusively on medications that provide some symptomatic relief, but they do nothing about the underlying cause. The problem we observed early on was that diseases caused by our behaviors are consuming almost 90% of all healthcare dollars in cardiometabolic disease. We spend about half-a-trillion dollars on medications to treat symptoms and nearly nothing on causes, but we know there’s a solution.
We know from the medical literature that intensive cognitive behavioral therapy performed by proficient healthcare practitioners with patients one-on-one can result in behavioral changes that can last a lifetime. So, our hypothesis was based on whether we could create software that could deliver a new form of behavioral therapy done entirely digitally that could treat disease by changing behaviors. That was what we set out to do when we started the company.
What’s emerged over the last several years is the name for what we do. It’s called prescription digital therapeutics. These are software products that physicians prescribe in our world by primary care. They are used by patients on any smartphone. Those prescriptions are reimbursed by insurance, just like a traditional medication. Aside from the fact that we use digital technologies instead of chemistry or biology to create our therapeutics, everything else works largely the way healthcare works: a physician diagnoses and prescribes that prescription that flows through a pharmacy and lands on a patient’s smartphone. And when that prescription is filled, we get reimbursed just like a drug.
We’ve now developed the software platform, and we’ve run multiple clinical trials pertaining to diabetes and heart disease and seen consistent signals efficacy with almost no adverse side effects. We’ve also advanced our first product for treating type 2 diabetes into a pivotal trial. We’ll use the data from that trial as part of an FDA submission next year.
GEN Edge: Why did Better Therapeutics choose to address cardiometabolic diseases with digital prescription therapeutics?
Appelbaum: Our invention is in the form of CBT specifically designed to treat the causes of cardiometabolic diseases. Some companies, like Pear Therapeutics, focus on substance abuse and have products on the market now for substance and alcohol use disorders. Others have developed prescription digital therapeutics for mental health like adolescent ADHD. Any class where we know the causes to be behaviors, choices made by people each day will likely be a target for prescription digital therapeutics, if not ours, then somebody else’s.
We have a clinical development pipeline, and our lead product is for treating type 2 diabetes. We have several other products in development based on hypertension, high cholesterol, and fatty liver disease—indications that share common pathophysiology such that if our products are successful in one, like in treating type 2 diabetes, we have every reason to believe they’re going to be effective (with some minor modifications) in treating other conditions. We have the burden of designing and conducting high-quality clinical trials to show that our products are safe and effective in each of our target conditions. And we have to build the evidence based on real-world studies that give us the information we need to engage insurance payers in discussions around coverage and reimbursement.
So, like a traditional pharmaceutical company, we have a pipeline of products. They’re at different stages of development. Each of them has to go through the clinical and regulatory path before commercialization. We plan to commercialize with our own team to uniquely bring new digital prescription therapeutics to market in primary care.
GEN Edge: What is Better Therapeutics’ approach to research and development (R&D)?
Appelbaum: We call it product development. What’s unique, if you look under the hood, is instead of having PhDs in chemistry and biology, we have software engineers, user experience designers, and product managers. We look like a software company under the hood in the way we do R&D. That kind of traditional structure of engineering design and product manager management is married with a team of clinicians. The guidance and inputs for product development come from a clinical foundation software is developed, and then it’s tested just like a traditional medication.
We don’t have phase I, II, and III trials; instead, we have early clinical discovery, pilot studies, and digital studies. It’s a different modality, but the system kind of works the same way. We’ve got the same quality requirements even though we’re not manufacturing a physical good. We have to adapt things that were created for the manufacturing of physical products to the design and deployment of software technologies. But that’s more in the details than it is in concept. It works largely the same.
GEN Edge: What is the clinical testing journey like for digital therapeutics?
Appelbaum: We don’t have to worry about mice! Our therapeutic mechanism of action is based on a new form of behavioral therapy that’s principally focused on how we eat and live. We learn about how that mechanism works to treat disease in humans. We start with usability testing; we ask: is the software working in an intuitive way that patients can engage with and stay engaged with, and do those engagements result in outcomes? Then, we escalate the quality of those studies from single-arm, non-randomized, non-blinded to randomized, controlled, pivotal trials to generate FDA quality data.
It’s very free-thinking. This is a case where difference is good because what we’ve been doing for decades isn’t working; somebody has to blow the whistle and say, ‘Stop!’. We’ve seen several dozen diabetes medications in the last decade-and-a-half, costs are up two-and-a-half times in 10 years, but people aren’t getting any better — in fact, they’re getting worse. Less than half of people being treated for type 2 diabetes can achieve the goal of that treatment, which is the lowering of blood sugar to a certain level. More than half of the patients can never get their diabetes under control.
We will have to start looking at what we’re doing and ask why we keep doing it the same way if it’s not working and people are getting worse. Our proposition is, if you want to make a change, you better do something different. Let’s start focusing on the causes instead of the symptoms of the disease.
GEN Edge: Will Better Therapeutics enter the international digital prescription therapeutics market?
Appelbaum: Certainly, distribution is not the hard part for a digital product. Our focus internally is to build an organization that will commercialize our products directly in the United States. The therapeutic problems that we solve are global problems. The need for therapeutics that can address behavioral root causes is global. The opportunity is so big for us right now, just in the U.S., that it’s going to keep us occupied for a while. If we create a vehicle for commercialization outside of the U.S., it would likely be with partners.
The other part is this: our product is unlike a medication where one should work for anyone else who has a similar diagnosis. Regardless of borders, the behavioral therapeutic has some unique aspects. Our behaviors are primarily driven by how we were raised as children, the environment we live in, and the socioeconomic pressures we face. There would be, need to be some work around how does, how does a behavioral therapeutic translate across culture and geography that you wouldn’t have with a medication.
GEN Edge: What is the process for updating prescription digital therapeutics?
Appelbaum: It’s an evolving landscape. Our therapeutics and software are, by nature, continuously improving. We use artificial intelligence algorithms to tailor the treatment to each patient. So, unlike a drug, no two patients get the same medication. The parameters of treatment are adjusted for each individual. Think of it the way Google would think of a search algorithm. Every time an individual performs a search, the quality of that algorithm gets a little bit better. At some point, you have so many searches being done over and over again that you have an advantage that is just based on an algorithm that is highly trained.
We have that opportunity as well. Every patient we treat generates thousands of data points related to their engagement. Those data point our inputs into a treatment algorithm that allows us to become better and better over time. Our therapeutics are continuously improving. The FDA recognizes that unlike a drug, which is a fixed molecule, that’s going to stay fixed. We have the opportunity to make products better and better time without introducing safety considerations. So, there’s a methodology that we have in place to look at changes to evaluate whether those changes are substantial or not. And if they are, there’s a regulatory pathway for dealing with things that would represent substantial change or improvement. Still, if they aren’t, if they’re really around user experience and clarity and usability, then there’s a different way we treat those.
We’ve got a growing commercial team. The naming and branding of the prescribable therapeutics is an art and a science in itself. But there are external agencies that we work with to do some of that work. Like most things, particularly things commercially related, we have executives inside the company that run those initiatives. Then we have external experts that we partner with on things like naming and branding and design.
GEN Edge: What’s next for Better Therapeutics?
Appelbaum: Our near-term objective is to get our first product for treating uncontrolled type 2 diabetes through regulatory approval and a launch of that product in 2023. The success of that first product enables a lot of good stuff to happen. The company’s value will grow, give us access to capital, and let us advance and accelerate other products in our pipeline. But all of that work is going to be the outcome of a successful first launch in type 2 diabetes.
If we look farther forward, what we’re aiming towards may take us a decade to get there. But it’s hard to come up with a rational argument for not making a digital prescription upon diagnosing any cardiometabolic disease.
Why would a physician not start with a prescription that addresses the behaviors that are causing the disease in the first place? Ultimately, we think our products and others treating other conditions are on a pathway to be the first prescription ever written. If that’s the case, then there’s a unique opportunity to think about just transforming the whole system of care for cardiometabolic diseases. We are moving away from this one drug/one target myopic focus of pharmaceuticals. Let’s look at the entire system in its parts that starts with therapeutics and patient services and use patient-generated data to inform clinical decisions and insurance products. There’s the opportunity to do a fundamental rethink for how we treat the most common and costly diseases.
