Brexpiprazole

Johan Luthman has been running R&D at Lundbeck since 2019, and part of the neuroscience leader’s remit is helping steer development of a promising but still-experimental seizure medication that the company acquired last year in its $2.6 billion buyout of Longboard Pharmaceuticals. Endpoints News sat down last week over Zoom with Luthman as researchers descended on San Diego last weekend for the American Academy of Neurology’s annual meeting to discuss the latest data and advances in the field. The conversation touched on neuroscience’s evolution, the dichotomy between psychiatry and neurology, and what’s next for Cobenfy, the schizophrenia drug at the center of Bristol Myers Squibb’s acquisition of Karuna Therapeutics. This conversation has been edited substantially for length and clarity. Max Gelman: Thanks so much for taking the time to chat. How has neuroscience R&D changed in the last few years, particularly after the pandemic and recent Cobenfy approval? Johan Luthman: I can go on for two hours on this one. I often get the question from people: “Why do you stay in an area that is so hard?” And I usually say it’s not that hard if you do it right. Neuroscience is actually a good space to be if you do it right, and you do it from a biologically solid platform. “Let the biology speak,” as I call it, and you sort it out in early development. Take your risk early. And some people often miss this. If you look at a drug’s chance to go to the market, it’s actually a lower chance for an oncology drug than a neuroscience drug. Gelman: Historically, what’s made neuroscience so challenging? Luthman: We’ve had our shares of Phase 3 negative readouts, for sure, and that is part of the perception. I worked for years in Alzheimer’s disease, and the problem is because of the self-reported outcome measures that we often have or are caregiver-reported. It’s seldom death. It’s seldom physiological measures. But we’re getting there more and more today. We’re rewriting a little bit of the textbook, particularly on neurology. Psychiatry is still a symptom-defined diagnosis. Gelman: What are the main differences between neurology and psychiatry? Luthman: In psychiatry, you go to your doctor and say, “I have some bad days, and I had those bad days for six months.” Yes, you have maybe a depressive disorder. So we’re still quite primitive in psychiatry. But in neurology, we’re moving fast, and we also work in neuroendocrinology, and that’s really where you have very solid endpoints. So there you have to pick your battles where you can sort it out. Gelman: You’re talking about biomarkers here, right? Why has biomarker research been more prominent in neurology research versus in psychiatry? Luthman: Psychiatry, we don’t know what’s going on in the brain. You ask someone how they feel, and you put that together in some measure, like the DSM-5 diagnostic manual, and you bundle all these symptoms together, and then you diagnose someone. That’s very soft science. Self-reporting is unreliable, and it’s based on symptoms that may occur because of underlying biological changes. We have many more possibilities for biomarkers in neurology. Space imaging, PET imaging, MRI imaging, fluid biomarkers — there’s a pretty rapid progression of new tools to look at treatment effects directly on pathophysiology. Gelman: How do you translate this understanding of biology and physiology into drugs that work? Luthman: There are some attempts to do more [of] what we call “personalized medicine” in psychiatry. But if the starting point is still a symptomatic one, or maybe something at the system level, it’s much harder. We really need to go beyond that. Are we there? No. Absolutely not. This will take a long time. Gelman: Are there any recent examples of companies trying to do these personalized medicine approaches? Luthman: We took a classical psychiatry drug into Alzheimer’s disease recently, together with Otsuka, for agitation and aggression in Alzheimer’s disease, which, by the way, is a much more problematic symptom than cognitive deficits. [Editor’s note: The FDA approved Lundbeck and Otsuka’s drug Rexulti in 2023 in this indication.] You mentioned the Karuna drug Cobenfy, and the big acquisition there, right? They are also bringing drugs into that space now. The pioneers here were Acadia, who took a drug into psychosis in Parkinson’s. But we’re following that trend, and I think there’s lots to be done between psychiatry and neurology, in both directions. Gelman: How do researchers bridge this gap? Luthman: This division about psychiatry and neurology is a very artificial one. It’s not particularly useful. But, clinically, they are so separated, and the mindsets are so separated. We need to have great psychiatrists helping move psychiatry drugs into neurology, because neurologists are not particularly well-trained to handle those drugs. The other one is to go the other way around. We really need psychiatrists to think like neurologists. They need to look at the brain. We need to get beyond Freud and Jung, and we need to get back to biology. Gelman: What has to happen in order to get a broader industry-wide buy-in and not just a select number of companies? Luthman: That’s a big question. I cannot pretend that I have the wisdom. I’m just a humble servant of this. I’ve done it for many years, and I’ve seen a lot of things not working out. So you learn through your scars. I think generally in neurology and psychiatry, we can learn a lot from how people do it in other fields. The cardiovascular guys brought a lot of value to stroke prevention. A lot of the good drugs that came into MS came from oncology and from immunology. So we have to be very open-minded. Gelman: Johan, I really appreciate the time, thanks so much. Luthman: Thank you.