Janssen Research & Development, LLC: The best of times and the worst of times for neurosciences




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Video title: Janssen Research & Development, LLC: The best of times and the worst of times for neurosciences
Released on: August 23, 2012. © PharmaTelevision Ltd
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In this episode of PharmaTelevision News Review, filmed at #BIO 2012 in Boston, Fintan Walton talks to Husseini Manji, Global Therapeutic Area Head, Neuroscience, Janssen Research & Development, LLC. This interview was filmed prior to the announcement of the results of the Janssen Alzheimer Immunotherapy led Phase 3 trials with bapineuzumab IV in mild-to-moderate AD.
Husseini K. Manji's perspective: Challenges in Neuroscience
Fintan Walton:
Hello and welcome to PharmaTelevision News Review here at BIO in Boston, in 2012. On this show I've got Husseini Manji, who Heads up Neuroscience Research and Development at Janssen Pharmaceuticals, welcome.
Husseini K. Manji:
Thank you. Pleasure to be here.
Fintan Walton:
The name Janssen is closely tied to Paul Janssen of course and he was a great founder of neuroscience and now you head up Neuroscience at Janssen Pharmaceuticals which is part of the Johnson & Johnson family of companies, what are the big challenges at the moment for neuroscience?
Husseini K. Manji:
So it's a real honor and a pleasure to walk in those footsteps as you said Paul Janssen the real giant in the field having discovered some of the most important drugs for neuropsychiatric disorders over 50-years ago and has a very long standing legacy, in fact that's one of the reasons I joined the Janssen I was at the National Institutes of Health for 15-years and joined Janssen about three and a half years ago primarily because of the legacy. I think it's in someway is the best of times and the worst of times for Neuroscience , in terms of the best of times there is just an unprecedented explosion in terms of our understanding about the fundamental molecular and cellular underpinnings of both normal and abnormal brain function ways to image it, ways to manipulate it, ways to come up with biomarkers, et cetera, so it's a terrific time for Neuroscience. The challenge is it's also the most complicated field there is so in terms of the complexity of the disorders there is nothing more complex than trying to understand the basis of the basically higher order brain function, thinking, emotion sensory those are things that are very difficult to just model in rodents also the brain tends to be relatively inaccessible so you can't just do a biopsy and see what's there. So I think that's been part of the challenge, a big another part of the challenge is that generally speaking we think these are heterogeneous groups of disorders where they calling it Alzheimer's, or Parkinson's, or schizophrenia that we lump together under one category we haven't had the real biologic way to sub-divide them so that we could say okay this is an Alzheimer's patient who is gonna respond to this, or a Parkinson's patient who is going to respond to that, so that adds to the challenges and I think at any time you are trying to do ground breaking work like slow down the progression of Alzheimer's disease or treat severe depression in hours rather than weeks, the territory hasn't been charted so everything is new and I think that adds to some of the challenges in terms of what we're trying to do.
Husseini K. Manji's views: Time spent on understanding fundamental disease biology vs drug development
Fintan Walton:
Because that comes right into the heart of pharmaceuticals in a way or even in the discovery of drugs, because if it is the ultimate challenge isn't it, in that respect because as you say it's the diagnosis, is the understanding, the fundamental understanding of the disease and to be able to find out about drugs that are in earlier stage rather than having to wait for the Phase III clinical trials to come through is really fundamentally important, so how do you divide the time that you need to spend on understanding the fundamentals to the various diseases that you've described versus the time that you spend taking a single molecule all the way through clinical trials?
Husseini K. Manji:
I think that's an excellent question and I'd like to believe we actually spend a 100% time on both and I will explain it how we are trying to do that is I really think the fundamental disease biology, I think that actually is better done outside the pharmaceutical industry so with academics, with the government like the NIH, the MRC, the Wellcome Trust I think that's what they do well, they don't do well targeting the biology for treatment. I think in someways the pressure is on the system, but perhaps particularly with Neuroscience is really fascinating formal collaborations so we are finding a much greater willingness for people to come together and to do a lot of the fundamental work together with academics, with different pharmaceutical companies, with different governments with the understanding that the knowledge will benefit everyone, once you get to a certain stage then the race can start we can try and develop our molecule, Pfizer there and so on, so I think we really do believe that the greatest advances comes from understanding the fundamental biology, but there is people who do that better than we do and lets try and partner with them, working with them to understand the biology and then helping them to interrogate if you really manipulate this pathway is your read out as desired. Another area is in the area of biomarkers and I think in the Alzheimer's space perhaps it's been one of the greatest success stories that something called ADNI which stands for Alzheimer's Disease Neuroimaging Initiative now something that's formed about five or six-years ago, the National Institute of Aging came up with a lot of resources and about 20 companies including ours joined it and the idea there was that almost certainly for something like Alzheimer's disease you gonna have a greater effect if you can get in early in the disease by the time a lot of neurons are dead even if your target is correct, the damage has been done. So that backs the question how do you identify people who are on their way and this ADNI initiative was able to follow people before they had Alzheimer's, follow them for years with different biomarkers and now we are at the point where with some of these biomarkers you can predict with very high confidence who's on their way and who isn't, it could not have happened with any one company or presenting it alone, but now we all reap the benefits, so we try to do both.
Janssen Pharmaceuticals's clinical program and Major breakthrough in Alzheimer's
Fintan Walton:
So I suppose the key thing you are bringing out there is this concept of personalized medicine or stratified medicines sometimes called, is really the subject for Neuroscience because in the end it's really getting down to the diagnosis, the very clear differentiate diagnosis you can get for even one single disease like Alzheimer's or schizophrenia and so forth, so in that journey that we are all embarked in our society or the world is embarked in, how close are we now? I mean are we still quite distant away from really fundamentally understanding the diseases and what time span do you think will be required to get really into the knowledge of that particular area?
Husseini K. Manji:
So I think we may be on the verge of some major breakthroughs and Alzheimer's disease is one of those examples, where since Alzheimer sort of the disease is named after Alois Alzheimer and over 100-years ago he noted that in the brains of individual Alzheimer's disease that these things called amyloid plaques and neurofibrillary tangles, for long time it wasn't know are these simply scares when brain tissue dies, or are they fundamentally causative and the lot of human genetic and other studies suggested that there is some how causally related that let to the study to look at well if we removed them from the brain would you have benefit and certainly in mouse models of Alzheimer's you were able to sort of remove them and see improvements in learning and memory so that led to large scale clinical trials, Janssen and Pfizer has one and again this is taking people with what's known as mild to moderate Alzheimer's disease treating them with an immunotherapy and monoclonal antibody designed to target amyloid and remove it from the brain and basically the patients are followed over 18 months to see if doing that slows down the decline and does it slow down basically neurodegeneration, by the end of the summer the results of the large Phase III studies from those trials will be available. Lilly has a similar program with another antibody called solanezumab once again by the end of the summer the results would be available.
Fintan Walton:
And these antibodies can cross the blood-brain barrier, so it's not a huge difficulty to use these into (indiscernable)?
Husseini K. Manji:
Correct, our thinking is that only a small amount needs to cross the blood-brain barrier, it sort of accumulates around the area of the amyloid plaques and in fact works in a catalytic function so certainly not massive amounts get in but we know that some amount does get in and we think it's sufficient and we have evidence in human beings using imaging that you are lowering amyloid, so you can take people and study amyloid in the brains at base line, treat them with the antibody and show that amyloid levels are low, the question that these studies read out is does that help at this stage of the illness.
Fintan Walton:
And what's the clinical endpoint there? What are you looking for?
Husseini K. Manji:
So there is couple of clinical endpoints, one is a cognizant score something called ADAS-Cog that with attempting to see if you can slow down the rate at which it declines. One of the challenges in the field coming back to your one of your other questions is that this was a scale that was developed for symptomatic treatments, things that help the memory a little bit, they weren't designed to show that you are slowing down progression of disease, so that's one of the challenges you still have to use the scales that are available FDA approved et cetera, but it may not be the best scale for this purpose nevertheless that's one of the scales we are using, another one is a disability scale, so the question is okay will you slow down someone's decline on the ADAS-Cog by 4 points a year so what, does that mean that they can live independently, can they drive, can look so there is also there is sort of functional scale to say okay if you slow down the decline what is it translate into functionally and then there is number of different biomarkers, one is to show that you are reducing amyloid in the brain, the other one is to show that unfortunately in Alzheimer's disease what tends to happens is that the neurons are shrink and die overtime, so with repeated MRI to show that the rate of shrinkage has slow down, and then there is another biomark you can measure in the spinal fluid something called phospho-tau it sort to represent a mark of neurodegeneration so to show that you are slowing down degeneration by measuring the biomarker, so it's a very intensive study.
Fintan Walton:
Right, so slowing down is one thing of course, is it ever possible to be reversed?
Husseini K. Manji:
Yes, again we think so, but you know baby steps.
Fintan Walton:
Early days?
Husseini K. Manji:
It's early days, so certainly I think we think if this works the next big thing will be to get in as early as possible. So we certainly think that you go from healthy neurons, to sick neurons, to dead neurons, but the time the neurons are dead then it's gonna be difficult to replace them, but at the sick neuron stage if you remove the toxin then can you restore these to health and we certainly believe so, but it's sort of starting with can we slow down and then move it earlier to early in the disease can we even prevent you are developing Alzheimer's and you've got prodromal but you don't actually develop Alzheimer's and then in the prodromal stage can we reverse it, that would be the ultimate goal. One of the other big areas for breakthrough is as I was just mentioning people often don't appreciate just how disabling severe depression is and more people die from suicide in the US every year that only three forms of cancer, so it's a number one cause of disability and a fatal illness and all our treatments currently take weeks to work and only work in about 30% of people et cetera, but when some tremendous breakthroughs that suggested if you hit the right target, you can treat severe depression within hours and again that could be sort of a completely novel breakthrough area. So I think there is a lot of positives, there is other areas where we still have a long way to go, but the hope is that if this Alzheimer's treatment if it works, if some of these rapid-acting antidepressants work et cetera that I'll think give the feel a little bit more confidence that this is not as much of a black box as we sometimes assumed.
Future products in Alzheimer's and schizophrenia
Fintan Walton:
So with the Janssen Pharmaceuticals your own products coming through, which ones should we look out for?
Husseini K. Manji:
Yes, so I think certainly the Alzheimer's drug is called bapineuzumab and as I said later this summer we will have the results and I hope if the results are good enough we will move forward and file, if the results are not good enough we will do more work. So I think that's one of the ones we're excited about. We are working on an antidepressant that will theoretically work in hours and again we would be we think that could be very transformational. We are working on something that is a formulation change but we think could be staggering, so with in schizophrenia the biggest cause of relapse is not being on medication, so people stop their medication they relapse and they get rehospitalised is because of that. The side effects and what's interesting is that it's fundamentally a disease that affects your brain and your inside, so sometimes you are not even convinced you are ill, so we are working on a formulation which is an injection that you could have four injections a year and have the coverage and that's not gonna cure schizophrenia, but we have lot of reason to believe that will have a huge impact on relapse and in condition like schizophrenia the relapse we think is not only so devastating for individual in a family some data to suggest that each episode is almost toxic to the brain. So each episode actually causes more and more (indiscernable) sort of have this downward course, if there was a way to prevent that and again it will be a formulation change, it could be as important as a brand new treatment and certainly worldwide, villages in China and places like that where you don't have the medical infrastructure if you got a four injections a year that would be very exciting. The last molecule I mentioned is our molecule and is called Fulranumab which is anti-nerve growth factor antibody that shows remarkable efficacy in pain, and both Pfizer and Janssen have these molecules that from an efficacy standpoint look quite a bit better than opioids, non steroidals et cetera and a completely novel target and again the idea that you could treat severe refractory pain without sedation, without some of the addiction concerns some of those other things that would be a game changer.
Fintan Walton:
S o another angle into pain obviously is always welcome?
Husseini K. Manji:
Absolutely, you know I think that's a thing that we have plenty of treatments but they are far from optimal and a lot of side effects and pain sort of can be very disabling as well.
Fintan Walton:
Husseini Manji, thank you very much indeed for coming on the show.
Husseini K. Manji:
My pleasure, thank you.
Fintan Walton
Dr Fintan Walton is the Founder and CEO of PharmaVentures . After completing his doctoral research on the genetics of cell proliferation at the University of Michigan(US)and Trinity College (Dublin, Ireland), Dr Walton gained broad commercial experience in biotechnology in management positions at Bass and Celltech plc (1982-1992).
Husseini K. Manji
Global Therapeutic Head
At the time of recording this PTV interview Husseini K. Manji serves as Global Therapeutic Area Head, Neuroscience, Janssen Research & Development LLC . In this role, Husseini has end-to-end responsibility in bringing science and medicine together with global world-class capabilities in research and drug discovery, biomarkers, translational medicine, and disease area clinical development expertise. In addition, he leads a global team focused on combining innovative internal and external approaches to discover and develop new solutions for neurologic, psychiatric, and pain related diseases with a high unmet need for effective treatments. He was previously Chief, Laboratory of Molecular Pathophysiology & Experimental Therapeutics, NIH, and director of the NIH Mood and Anxiety Disorders Program, the largest program of its kind in the world. He is also a visiting professor at Duke University. Dr. Manji received his B.S. (Biochemistry) and M.D. from the University of British Columbia. In addition to his neuroscience research, and biomarker and therapeutics development endeavors, Dr. Manji has also been actively involved in medical and neuroscience education undertakings, and has served as a member of the National Board of Medical Examiners (NMBE) Behavioral Science Test Committee, the Howard Hughes Medical Institute Research Scholars Program Selection and Advisory Committee, and numerous national curriculum committees.
PharmaVentures
PharmaVentures is a corporate finance and transactions advisory firm that has served hundreds of clients worldwide in relation to their strategic deal making in the pharmaceutical, life science and healthcare sectors. Our key offerings include: Transactions / deal negotiations; Product / technology valuations; Deal term advice; Due diligence & expert reports; Strategy formulation; Alliance management; and Expert opinion for litigation/arbitration cases. PharmaVentures provides the global expertise to ensure our clients generate the highest possible return on investment from all their deal making activities. We have experience of all therapeutic areas and can offer advice on both product and technology commercialisation.
Janssen Research & Development LLC
Janssen Research & Development LLC formerly known as Johnson & Johnson Pharmaceutical Research & Development (J&JPRD), provides research and development support for the pharmaceutical business units of parent company Johnson & Johnson. The company divides its main research processes into three franchises: central nervous system and internal medicine; biotech, immunology , and oncology (in concert with fellow J&J subsidiary Janssen Biotech); and virology (with another J&J unit, Tibotec). The subsidiary which represents the largest segment of J&J's pharmaceutical R&D also does research in collaboration with other pharmaceutical organizations and biotech researchers.