Interview: Behind the E-mmunotherapy Earbud That Could Treat Arthritis
Non-invasive stimulation company Nēsos recently announced that its “e-mmunotherapy” earbud has been granted breakthrough device designation by the US Food and Drug Administration (FDA) for patients with rheumatoid arthritis (RA) who have had an inadequate response or intolerance to disease-modifying anti-rheumatic drugs (DMARDs). We spoke to Konstantinos Alataris, president and CEO of Nēsos, to find out more about the company's device and its potential applications.
Ruairi Mackenzie (RM): What is e-mmunotherapy?
Konstantinos Alataris (KA): E-mmunotherapy explores the connection between the central nervous system and the immune system. Uses engineered electrical signals to modulate the immune response. It's becoming more and more clear that those two systems are in constant communication and interaction.
We're trying to explore the relationship between autonomic nervous system dysfunction, inflammation control and disease development in rheumatoid arthritis (RA). We are intervening to address the autonomic dysfunction in an effort to produce a therapeutic effect for RA patients. The data recently published in the Lancet was from our first-in-human proof-of-concept study. It was conducted in Europe and gave us a preliminary signal. That enables us to take the next step in clinical development, which will be larger-scale randomized control studies in order to further investigate the link between restoring autonomic nervous system dysfunction as a potential treatment for RA patients.
RM: How was the Nēsos earbud used in the proof-of-concept study and how does it bring about its effect?
KA: The earbud delivers the engineered neural signal that aims to restore autonomic dysfunction. We're using the branch of the vagus nerve in the ear as a wire to deliver the therapy. In simple terms, it is a sequence of electrical pulses that the user cannot feel.
In the first study, the users were wearing the earbuds daily. This study has enabled us to figure out the appropriate parameters and monitor patient compliance. Patients were willing to participate in the study and were disciplined to use the device every day. We had north of 90% compliance rate and that resulted in an impact in their clinical symptoms. The other important thing was that we saw a sustained effect through this short daily use, not something that just lasted a little bit after each stimulation period end. So that was encouraging to us that we were able to see a sustained effect for the duration of the study, which was three months.
RM: What kinds of treatments would people in your recent trial have undergone before enrolling?
KA: In this proof-of-concept study, the vast majority of patients have finished the first-line therapy, which is always methotrexate or other disease-modifying antirheumatic drugs (DMARDS), and they had an incomplete response to DMARDS. There were a few patients that had already shown an incomplete response to a biologic, but most patients were methotrexate incomplete response patients and that's the patient population that we're targeting going forward as well.
RM: Some of your trial participants saw an ACR70 reduction (corresponding to a 70% improvement in symptoms) while others experienced lesser changes. What factors do you think might govern the response variability that you saw?
KA: The simple answer is: we don't know. We just don't have enough data right now in order to make some kind of a priori assessment on the level of response in each patient. We haven't seen anything different than we would see with existing drugs where you always have a range of responses between ACR20, ACR 50, ACR 70. For us, it's just too early in the development to have enough data points to better understand who would be a super responder and who would not.
RM: What are the next steps for the Nēsos and how will the FDA's breakthrough designation help?
KA: The FDA breakthrough designation does two things. It allows us to have a more interactive discussion allows for expedited review and I think will help with patient access after an FDA approval. So now we're in the process of defining the next steps of clinical development, which includes randomized placebo-controlled studies where half of the patients are on placebo. That's the typical development process, so we're not doing anything new, we are just taking the next step, and we've already initiated the discussions with the FDA in order to see what it will take in order to get the product approved.
RM: What other immune conditions do you foresee e-mmunotherapies being deployed to treat?
KA: It all has to do with the reach you can achieve with your signal, what kind of pathways you can target and how effectively you can retune them. Clearly, we're targeting pathways that control inflammation or can potentially control inflammation, and we're looking at diseases that are inflammation-mediated. So, for us, the next step would be in mental health. And we've already initiated a proof-of-concept study in a depression subpopulation because, based on our advisors’ feedback, psychiatric diseases are inflammatory-mediated diseases as well.
Also, we have a study in migraine prevention because again, there is a strong neuroinflammatory component. So those are the other two areas. Migraine is much more explored with stimulation and there is a neurological pathway established by previous studies.
With mental health, you have approaches that are implantable – specifically for depression- but our approach in mental health with a non-invasive therapy, if that proves to be effective, could provide a very important alternative treatment option.
RM: When targeting different conditions, how specialized can the technology become?
KA: At my previous company, Nevro, we developed an implantable spinal cord stimulation that uses different electrical signals to treat chronic pain. We've learned quite a bit there and specifically the fact that different waveforms, different frequencies, different electrical characteristics of your signal can have vastly different effects. As a result, the Senza system from Nevro received superiority designation by the FDA. In that previous effort, we are tuning a neurological pathway that controls chronic pain. In this current effort, we use different parameters for the electrical sequences=d based on the research that we continue to do with intracortical recordings and with functional magnetic resonance imaging (fMRI) work. Working with the ear, we get the benefit of non-invasive access and consistent coupling to the nerve, an afferent nerve, to allow delivery of the signal where we want in the brain.
Konstantinos Alataris was speaking to Ruairi J Mackenzie, Senior Science Writer for Technology Networks