Bill Meury, president and CEO of Karuna Therapeutics, speaks with WebMD Chief Medical Officer John Whyte, MD, about the differences in drug development in psychiatry and the importance of innovation.
www.medscape.com/viewarticle/...
-- TRANSCRIPT --
John Whyte, MD, MPH: Bill, thanks for joining me today.
Bill Meury: Great to be here.
Whyte: I want to start off by asking you, how is drug development in the field of psychiatry different from in other fields and disease states such as oncology or cardiovascular disease?
Meury: If you think about the entire drug development process, the first place you start is in preclinical studies. The predictive value of preclinical studies in central nervous system (CNS) development is different from in other therapeutic areas. That's number one. Second, you have to deal with the blood-brain barrier, which is very different from when you're dealing with compounds that are being developed for non-CNS conditions.
The population and these conditions are very heterogeneous, and there's a lot of variability between patients if you're in oncology, hypertension, or diabetes. Last, the endpoints in CNS drug development are not physiologic endpoints; they're subjective endpoints that require physician and patient interaction. So it makes the process a little more unpredictable, whether you're in early stages or late stages of development. That being said, there have been a number of breakthrough treatments introduced over the past 20-30 years. These barriers have to be managed and understood.
Whyte: The innovation that we've seen in some other areas hasn't necessarily been matched in this area - in particular, in schizophrenia and psychosis associated with Alzheimer's. On your website, you note that your goal is "transformative medicines." I want to understand what that means. Let's take, for instance, schizophrenia, in which 30% of patients may not respond to the drug and 50% may have an inadequate response - 50%.
Meury: That's right.
Whyte: So you're saying you're going to change that; it's going to be transformative. So I have to push you.
Meury: Sure.
Whyte: What does that mean, in practical terms for listeners?
Meury: Let's talk about some transformative innovations in neuroscience over the past 30 years. Innovation, as you know, is cyclical. And it's true that in neuroscience we have not seen a lot in the past several decades. But when the atypical antipsychotics were introduced for people suffering from schizophrenia, they replaced the typicals. And they had a fundamentally different benefit-risk profile. That class of medication, which was introduced in 1993, had a profound impact on people suffering from schizophrenia. A few years later, selective serotonin reuptake inhibitors (SSRIs) were introduced and completely replaced the tricyclic antidepressants. Depression, as you know, affects millions and millions of people, and the SSRIs were better than the tricyclic antidepressants. Most recently in migraine, for example, after decades of use of drugs called the triptans, calcitonin gene-related peptide receptor (antagonists) - CGRPs - were introduced. And in 3 years, about 1 of 3 three people are receiving a CGRP instead of a triptan. That's transformational treatment. So here we are in schizophrenia, and there hasn't been a novel mechanism of action - something that wasn't a D2 antagonist, basically - in 30 years. We have a product (KarXT) that pharmacologically is treating schizophrenia very differently; it's acting on the M1/M4 receptors in the brain presynaptically, whereas the atypical antipsychotics act on the D2 receptor, antagonizing them postsynaptically. (KarXT is under review by the US Food and Drug Administration. It is not approved for therapeutic use by any regulatory authority.)
The potential benefits of KarXT are such that we could see a new class of medications in schizophrenia, just like the other classes I mentioned: the atypicals, the SSRIs, and the CGRPs. And that's how I would define innovation. Ultimately it will be measured by how many physicians, after they evaluate the data, use the product and how many patients are taking the product. But I think it could have a profound impact, just like the atypicals did back in 1993.
Whyte: I want to come back to your examples of migraine and depression, and for conditions like schizophrenia, there's still stigma associated with it. We're scared of those patients, or we don't really understand what it is. We've made amazing advances in the treatment of depression, and even the recognition of it - certainly of migraine. What role does stigma play in what you're doing here, and how are you meeting patients' needs?
Transcript in its entirety can be found by clicking here:
www.medscape.com/viewarticle/...
8 дек 2023
