Josh Sackman: Immersive Pain Treatment & FDA Approval

Faaizah Arshad and Jessica Hagen speak with Josh Sackman, cofounder and president of AppliedVR, regarding AppliedVR’s FDA-approved RelieVRx platform for chronic lower back pain treatment and the steps to attaining FDA approval.

BIO

A decade of building businesses at the intersection of health and technology has culminated in Josh’s role as President and Cofounder of AppliedVR, a digital therapeutics company enabling remote pain care through prescription virtual reality therapeutics (VRx). It was Josh’s own experience with pain, anxiety and isolation as a pediatric patient that inspired him to make chronic pain more manageable for others.

The following is a transcript of the episode:

Faaizah Arshad

Hello and welcome back to Psychiatry XR, we aim to inspire worldwide conversations around the use of extended reality in psychiatric care. I'm your host for this episode Faaizah Arshad. I'm an undergraduate student at UCLA studying psychology and as an aspiring physician, I'm interested in understanding the ways in which we can leverage technology to improve health outcomes. I'm very excited to be joined by Psychiatry XR’s co-founder Jessica Hagen.

Jessica Hagen

Hi Faaizah happy to be here.

Faaizah Arshad

Same. Dr. Kim Bullock, Jessica and I created Psychiatry XR, a monthly podcast for all XR and behavioral health stakeholders, including clinicians, researchers, allied professionals, developers, investors, patients and anyone else fascinated by how evidence based mental health and technology intersect. In each episode, we invite a new guest to provide insight into the potential benefits, challenges and questions around immersive technologies in mental health care. Today, we're delighted to welcome Josh Sackman, AppliedVR’s Co-Founder and President. AppliedVR is a digital therapeutics company enabling remote pain care through prescription Virtual Reality therapeutics. It was Josh's own experience with pain, anxiety and isolation as a pediatric patient that inspired him to make chronic pain more manageable for others. After graduating with a business degree from USC, Sackman earned a bilingual MBA at IAE business school in Buenos Aires, Argentina. He then built a career in digital marketing with a focus on the fitness industry, eventually taking the role of CEO at cycle house, a boutique fitness firm. He's often a featured speaker at international conferences. Josh has a decade's worth of experience in building businesses at the intersection of health and technology. Thank you so much for joining us, Josh.

Josh Sackman

Thanks for having me.

Faaizah Arshad

AppliedVR recently released a product called RelieVRx. Tell us about RelieVRx? What is it? How does it work? And why is it particularly effective for chronic lower back pain treatment as opposed to other pain treatments.

Josh Sackman

So, RelieVRx was the first FDA authorized immersive therapeutic product for the treatment of at home chronic low back pain. We've been developing this product with Dr. Beth Darnall at Stanford, since about 2018. Though we initially started the business in 2015. We've been developing a program that really focuses on self-regulatory skills. And so this isn't just about helping patients mitigate symptoms while in a headset, but rather, teaching skills and education and things that equip patients to have more tools in order to manage their pain outside of the headset. And so over an eight week program, patients go through about seven minutes a day of different modules based in evidence based treatments rooted in diaphragmatic breathing, relaxation, mindfulness, distraction, attention control, and pain, neuroscience education. And the goal is when the headset comes off, patients are able to leverage these skills in order to not just reduce their pain, but improve their quality of life. And so over our pivotal trial, which we used to submit to FDA, which had 188 patients with chronic low back pain, patients on the average, over those eight weeks at the end of treatment, experienced 42% less pain, and improvements of up to 57% improvements in pain interference with things like mood, stress, sleep and activity. And what's most exciting about what we're doing is after we look six months post treatment, so that six months after returning the headset, patients are still maintaining a clinically meaningful reduction in pain and pain interference, which is a 30% improvement from baseline. And so it isn't just one year experience in VR that you're getting benefits. Six months after returning the headset, you're acquiring and retaining skills that continue to be applied to improve the quality of life. And so what's exciting about VR is we're delivering methods that can be delivered outside of VR: mindfulness training, diaphragmatic breathing and biofeedback, pain, neuroscience education, are all skills and approaches used for the treatment of chronic pain. But what we really enable patients to do is be able to do this in the comfort of their own home, on demand in a way that's more fun and effortless than going to traditional therapy or using the more traditional device. VR really taps into some really unique properties to allow, allow the technology to be able to tap into more nonconscious and emotional forms of learning that could lead to better retention, faster learning, and a more enjoyable process for doing things that are typically pretty hard to do. Behavior change is incredibly difficult. And so VR has unique properties that make learning and behavior change a little more attainable for a lot of people.

Jessica Hagen

RelieVRx, formerly known as EaseVRx is the first and only FDA authorized at home immersive VR pain treatment at this point. So FDA authorization just to give our listeners a little background, FDA authorization differs from FDA approval. Many people know a lot about FDA authorization because of the pandemic. For example, the COVID vaccines were provided emergency use authorization. For our listeners looking to obtain FDA authorization for a therapeutic, a VR therapeutic in particular, can you tell us what steps applied VR took to obtain that authorization and how the process works?

Josh Sackman

Sure, and when I say FDA authorized, what I'm speaking to is we took a de novo pathway with FDA. De novo means it's a first of its kind product without a predicate, meaning there existing products on the market. And so when you hear the word FDA cleared, you're typically submitting a product that's like another product that exists out there. And so if you're a neurostimulator device, you look at other neurostimulated devices, and you show comparable efficacy or equivalents to existing products out there. And so for us, we had to not only demonstrate the value of RelieVRx and its ability to reduce pain and pain interference, we also had to work with FDA to help establish this new category of device which didn't exist before. And so, for us, there was a lot of additional documentation process and conversations with the agency to help them understand this new category of delivery, immersive therapeutics, and not only how AppliedVR is approaching it, but how other companies will proceed in the same pathway moving forward. And so we took an approach to regulate our device as a SiMD, that Software in a medical device, which means the hardware and software were regulated. We thought that was particularly important, because a huge question is, how safe is this hardware in the context of medical care in the home, in which case, in our use case, it's unsupervised by clinician, so patients are self-administering the therapy in the home. And these patients have a chronic illness, chronic low back pain. And these patients may have pacemakers, other medical equipment in the home, and things that we had to make sure that we contemplate as we thought about the safety and the regulatory position the device. And so our device had to go through the same IEC certification and test in the same way any other medical device to show that it met the medical device in-home standards. And so I just wanted to clarify because often there's a question of, you know, is it the software, is the hardware, and in this case, it was a combination. And over time, the software may be more of the focus of regulation. But in this beginning stage, we've taken a very conservative approach to make the rebate to make sure we're very thoughtful in terms of the whole experience of bringing a new type of medical device into the home for self-directed care. When you think about FDA, the two things that they're focused on are the safety and efficacy. And largely, FDA relies on randomized controlled trials as a way of the gold standard of evaluating both of those things: the safety and efficacy. When we met prior to our submission with FDA, one of the key questions they had is, how much is your therapeutic program versus the benefits of VR, because putting on a headset in an immersive setting has inherent therapeutic qualities. You're blindfolded and earmuffed from the outside world. You're taking a break in this really novel experience that has a visceral impact and reaction from the patients or participants using the VR headset. And so the FDA asked us to include a sham control as a way for counting for the ritual, putting on a VR headset, and accounting for how much is the benefit of any VR versus a specially designed therapeutic program. And so our trial used a Sham, which was the same headset as you put it on and you enter the 3D interface. Instead of launching an immersive therapeutic module, we had a 2D plane, think of like a big screen TV with nature contact and so an eagle building a nest, a fox on a prairie, things that would be engaging and distracting enough to motivate a patient for doing this for eight weeks straight of daily use. But that removes some of the immersive qualities and a lot of the therapeutic kind of nature of the content to really create something that was a sham— that had no therapeutic benefits outside of the placebo benefits, and whatever benefits you get on from putting on a headset. And so I wanted to call that out because I think that's particularly important when thinking about companies that are trying to really demonstrate the clinical value of their product. There's a natural amount of skepticism, with anything new, but especially in the medical device and in this digital therapeutic realm. And so you have to contemplate these questions of how can you demonstrate superiority over something that can be cheaper and easier and better understood. And that could be an app downloaded on a phone, it could be downloading an app from the Meta application library, and other things like that. And so that was a really important part of our process, is running a really robust trial that used a really rigorous control. And then as we have the data to support what we're doing, FDA looks at the safety as measured by adverse events and the trial, the testing of the hardware to show the electrical safety and magnetic interference, and that we have a risk management plan to understand all the risks associated with the device and what we do associated with those risks, as well as being able to articulate the benefits as evidenced in the clinical trial. And so you package up a summary of this benefit risk story of showing what benefits are there, how much uncertainty exists because there's never 100% confidence in any data or, you know, definitive conclusions from a study, and then what are the risks and what uncertainty is there around how you manage those risks. And in total, it was about a nine month review process that was highly interactive, a lot of back and forth with FDA, which ultimately supported the authorization of RelieVRx, as well as the establishment of a new category of virtual reality behavioral devices for pain.

Jessica Hagen

Do you plan on seeking FDA approval for RelieVRx in the future?

Josh Sackman

So it's really confusing for a lot of people not familiar with the regulatory process as what FDA registered, FDA cleared, FDA authorized, FDA approved means. So FDA approved pertains to the class III pathway. So that's the highest risk of medical devices. Those are things like a pacemaker, or an implant in the body, which require a different level of rigor testing, to make sure that those are safe and effective when they could be responsible for sustaining life of a patient or implanted and propose a lot of risk. And so we don't see virtual reality therapeutics as rising to the risk level or classification of class III, at least as it stands now. Who knows what the future looks like, and what the application is . It largely depends on the intended risk and the claims you're making. But we expect to continue seeking indications as a class II device, in which case, if it's a de novo application like ours, it's FDA authorized, or if we're building off or existing predicate would be FDA cleared. And the last category would be FDA registered, which is a class I device. And those are things that could be a tongue depressor, a band aid, or other devices that are really minimal risk. There isn't actually a review process associated with class one FDA registered devices. There is a registration process where you submit documentation, and the company still is responsible of having the quality management system to make sure that they're factoring in the safety and compliance of being a medical device manufacturer. But we'll continue down this class II pathway with our future applications and applications.

Jessica Hagen

Thank you so much for clarifying that.

Faaizah Arshad

So Josh, you talked a little bit about the importance of ensuring safety and effectiveness for clinical products that the general population would be using. And I'm curious to know more about the adverse events and risk factors that AppliedVR studied for RelieVRx? What were the randomized controlled trial findings? And were there any limitations? Can you just talk more about what research supports the effectiveness of RelieVRx?

Josh Sackman

Well immersive therapeutics are fairly low risk and safe. I think it is important to call out there's obviously risk associated with any medical intervention. And as we look at our trial results, and literature at large, um, first and foremost, certain patients tolerate virtual reality better than others. And so we did notice some transient symptoms which could be headache, facial discomfort, motion sickness, dizziness, with up to 20% of participants at one time over eight weeks over the trial, that didn't lead any of the participants to discontinue the study. And partly it is because we design our intervention to be roughly seven minutes on average per day. And so we're really developing the modules to be the minimal exposure to VR that maximizes the effectiveness and benefits that patients get. And we clearly articulate the protocol that if the patient is experiencing any dizziness, motion sickness, discomfort, to take off the headset and take a break, and that tends to resolve the symptoms, we also tend to take a conservative approach, at least with our clinical trials. And as it gets prescribed on a commercial basis, it'll be under medical supervision of a doctor to factor in the right, risk-appropriate decisions for how this gets prescribed. In our clinical trials, we had exclusionary criteria around patients that have vertigo, and high susceptibility to motion sickness and nausea, to make sure that we're setting up the right patient to use the product. And that also includes patients with cervical pain and facial pain or things that could preclude them from using a VR headset. And so I'd say there are factors that would prevent patients from being a good candidate for VR. But for patients who can tolerate VR as a whole, they tend to tolerate our therapeutic very well. And we design our content also to minimize movement and to minimize the range of motion needed to look around within the scenes. And to be done seated. And to be approachable for a novice, particularly patients in our trial who are up to 84 years old, as you think about who may be buying a VR or Meta headset. And so we really take those factors in to our program design or clinical trial design, and to make sure that we're setting up people to succeed in using our medical device. And as it relates to the benefits, I'll highlight the results that we saw and kind of the methodology we took. And so our five primary endpoints were pain intensity, and so that's a pain score on a scale from zero to 10. As well as pain interference with stress, mood, activity, and sleep. Those were also evaluated on a zero to 10 point scale of how much has pain interfered with stress, mood sleep and activity. We had a baseline period prior to actually get an enrolled in the trial, where patients completed a series of different questionnaires that included those endpoints, and a lot of other patient-reported outcomes. And then we collected pain scores twice a week over eight weeks, and collected a post treatment measure at that eight week threshold. And then we continue to follow the patient one-, two-, three-, and six-months post treatment, after they return the device to see how durable the results are. That is to say, what’s their improvement from baseline, even after returning the headset, even after completing RelieVRx. And so what we saw at the end of treatment was a 42% reduction in pain intensity. And we also and to benchmark that a 30% improvement is considered clinically meaningful. And all of our results were both clinically meaningful, and statistically significant relative to the performance to the sham. And then we saw improvements that were higher than that in terms of the pain interference that we saw. And six months post treatment, patients retained the clinically meaningful results, meaning was a 31% reduction in pain from baseline, six months after returning the device and significant improvements with pain interference. And so we're very pleased that not only patients were getting benefit when they had a headset, but they also got benefits after returning the headset as they continue to practice and retain the skills that they've learned.

Faaizah Arshad

And so many psychiatrists and clinicians really do value digital health and they want to integrate it into their own practices. How can providers use RelieVRx to see if they're interested in investing?

Josh Sackman

Right now, we’re at a really interesting inflection point for our business. We're moving from R&D Stage medical device, really focused on product development validation and regulatory approvals, to now looking at commercialization, and how this actually gets used in the real world outside of clinical studies. And so right now, we're in preparations for our first stage of market launch later this year. So the second half of this year, our product will be commercially available, starting out in some limited markets. This is a doctor prescribed payer reimbursement model. And so many people think having an FDA authorization or clearance is all you really need and then it's off to the races. But the reality is our health care system in the US is far more complicated than that. So in addition to developing the clinical evidence that we've been developing, we're also looking at developing the health economic data to support what value this creates in the healthcare system. So ultimately, while reducing pain and pain interference is very important, especially in light of the opioid epidemic and pain crisis that we're in right now, ultimately, in order for health insurance providers to the payers to adopt this, and to be able to assign a price, they need to understand how this fits into the patient journey, and the pain care paradigm. They need to understand how using a product like RelieVRx can impact healthcare resource utilization. Does this offset the use of high-risk drugs? Does this delay or prevent procedures? How does this impact other types of treatment patients are getting, which can be far more costly and risky than using something like an immersive therapeutic? And so we're in the process of finalizing recruitment for 1000 person health economic outcome research trial, where not only are we collecting patient reported outcomes, and looking at the clinical impact of RelieVRx, but we're actually partnered with Komodo Health to bring claims datasets, and allows us to match a certain amount of our participants to claims data and look both pre, during, and post treatment to see the impact we're making in terms of cost, as well as health resource utilization. And so it's going to take some time over the next 12 and 18 months to complete that study, and read out the data to understand that. So we're working on that prospective trial, as well as we're working with a number of payers across the country to perform pilots within their beneficiaries to see how this fits in and is this a part of frontline treatment? Is this part of pre surgical treatment? Is this part of, you know, a different part in the patient care paradigm, as I kind of spoke to before, and we're in the process now figuring out from a commercial side, who are the right patient candidates for this? What's the patient's selection criteria? And how do we assign value and price to this in the market? And so we're actively working with payers. At the same time, we're working with physicians, who are actively looking for solutions for their patients.

Jessica Hagen

And so on that note, I know that you had mentioned that it's, it's hard to find a lot of different positions that are like really interested in using the technology at this point, right, is that something like Faaizah had mentioned to kind of circle back to that does AppliedVR, does it actually offer RelieVRx to physicians free of charge to be able to have them tested at this point? Or is that something that's more providers need to purchase the product to be able to sample it for their patients?

Josh Sackman

Yeah, prescribers don't need to purchase the devices. So it's much like prescribing a pharmaceutical product, where they're writing a prescription. And then we're working with the health plan to work on the reimbursement and the disbursement of the device to the patient. And so we are working to develop an early adopter program with physicians providing samples and education to work with the HCPs to figure out how this is currently active in a number of markets and have an overwhelming amount of demand from the physician who are looking to actively prescribe this. So if physicians are interested, they can reach out on AppliedVR’s website and we're happy to open conversations demo the product and figure out if they're the right type of physician for early adopter program before this gets scaled and opened up to wider scope of prescribers and patients. So we do offer sampling programs, we are developing an early adopter program, the physician does not need to buy the hardware. It's not designed for in-clinic use. It's designed to be prescribed, sent into the home, and for the patient to use on a self-directed basis.

Jessica Hagen

And so there's a handful, if not more companies that have signed with large entities like huge pharma companies that have a plethora of resources, and they're really working to expand their portfolio and commercializing their XR offerings. I do know that your company has grown substantially over the past five years, and has its own valuable set of resources. Is one of the end goals of AppliedVR to commercialize its products. And it sounds like it is, how do you distinguish your offerings from other big players in the medical XR industry?

Josh Sackman

Yeah, we plan on commercializing our own product. It's not to say we don't value partnerships. We absolutely do. And we're actively looking to create partnerships with large health systems, different industry players, and we're very open to collaboration. At the same time, this is a fundamentally new modality of treatment that's highly nuanced. And ultimately, we think we need to be in control of how this gets shaped in the market, meaning how physicians and patients and payers get educated, how ultimately gets presented and pitched. And one of the biggest challenges that we've seen by relying on another sales force, like a pharmaceutical company commercializing their blockbuster drugs and products. But this is one, fundamentally different and very different than the prescription of a drug, or traditional devices. And two, the finance, the financial interests are so strong for these blockbuster drugs, how prioritized is RelieVRx going to be relative to the other products being presented to the same doctor? And so in this early stage, where we want to learn a lot about how to present RelieVRx into the market, how this gets used, who are the right patients, how do we communicate the right value, and how does this get implemented, what does infrastructure look like at scale, we get so many learnings from actually rolling this out ourselves. And it's not to say we might have a hybrid model or partnerships in the future. But the learnings at launch are so critical that we want to maximize the control and learnings from launching a new product like RelieVRx.

Faaizah Arshad

Thank you so much, Josh. I'd like to also thank you for sharing information about AppliedVR and its offerings to our listeners. Is there anything else that you'd like to share with our listeners?

Josh Sackman

I'd love to share how excited I am about the prospect of immersive therapeutics. And we really are looking for other companies, payers, physicians, policymakers to look at entering the space and considering the value of XR. And if AppliedVR can be a resource and helping evaluate that. We can't be doing this alone. And it takes a village to bring something as new and as complex as XR for health treatment to life. And so we're big believers, but we can't be the only ones. And ultimately, the success of this category relies a lot on reimbursement, because that's just how our, our health system operates in the US. And so we need to focus on evidence, we need to focus on demonstrating value. We can't sell the hype or novelty of VR if we can't demonstrate the clinical impact and the cost effectiveness and value of VR and our health system. And so we're really focused on developing the comprehensive, comprehensive evidence that all those stakeholders I mentioned need to see. And so others, as others are thinking about the space, it's really important to think about: what evidence are you developing, are you talking about your product in a credible way. Or are you over inflating the value? All I know after eight years in the space is VR isn't the best solution for solving all problems. If you don't need VR, it adds complexity, cost, friction, and a lot of other challenges. However, VR really has some unique properties. And so if you can tap into where VR is useful and better than other alternatives, better than if you could deliver this in a mobile app, but depending on the type of patient and use case, mobile apps fall short and a lot of ways and so really think about the unique value of XR and making sure that you're focusing on the evidence to support that and because there's nothing that will kill XR more than bad execution of XR, overinflated hype around XR, you know, lack of evidence that makes it easy to dismiss. And so we want to bring the serious credibility that this deserves when operating in a space like healthcare.

Faaizah Arshad

Thank you again, Josh. Your insight and time is so appreciated. And that's it for this episode of Psychiatry XR. We hope you gained a new perspective on extended reality use in healthcare and thanks for listening. This episode was brought to you by Psychiatry XR, the psychiatry podcast about immersive technology and mental health. For more information about Psychiatry XR, visit our website at www.psychiatryxr.com. Be sure to subscribe to the podcast and tune in again next month to hear from another guest about XR’s use in psychiatric care. You can join us monthly on Apple Podcasts, Twitter, Spotify, or wherever you get your podcast. Psychiatry XR was produced by Dr. Kim Bullock, Faaizah Arshad and Jessica Hagen. Please note this podcast is distinct from Dr. Bullock's clinical, teaching, and research roles at Stanford University. The information provided is not medical advice and should not be considered or taken as a replacement for medical advice. We credit and are grateful to Austin Hagen for music and audio production. See you next time.