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Scientists comment on the FDA approving Cobenfy (KarXT) for schizophrenia.
Prof Oliver Howes, Professor of Molecular Psychiatry, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London (KCL), said:
“Schizophrenia is one of the top causes of disability in the world, partly because current treatments only address some aspects of the illness and don’t work well for many patients. The approval of KarXT means that for the first time in 70 years we have a treatment for schizophrenia that works in a new way. This could be a game changer for people with schizophrenia as it offers choice and the potential to treat aspects of the illness poorly treated by our current treatments. There is a lot of research that needs to be done now to understand who it will help most. That aside, it is the most exciting development in many years.”
Prof Matt Jones, Professor of Neuroscience at the University of Bristol, said:
“This new drug promises effective treatment but – crucially – with reduced side effects. Though not approved in the UK yet, it’s obviously great news for people living with schizophrenia, but it’s also great news for psychiatric drug discovery at large. We’ve not hit upon new drugs for decades, and discoveries like this are reinvigorating the field, driving investment and innovation.”
Dr Lynsey Bilsland, Head of Mental Health Translation, Wellcome, said:
“Cobenfy is the first new pharmacological approach for treating schizophrenia in over 50 years. It works in a completely different way from any other currently used schizophrenia drugs. It has the potential to change the lives of millions of people.
“Schizophrenia is commonly treated with antipsychotics. While these can be effective in managing symptoms like hallucinations and delusions, they do not address other life-limiting symptoms such as social withdrawal and memory problems. Cobenfy has the potential to address all of the above symptoms and also has fewer side effects such as sleepiness and weight gain and therefore could be game-changing, especially for those for whom other drugs do not work.
“Wellcome supports mental health research to drive transformation in early intervention for anxiety, depression and psychosis. Cobenfy is an outstanding example of how science can drive forward more effective mental health treatments in our lifetimes.”
Prof David Curtis, Honorary Professor, UCL, said:
“This treatment does represent a really novel approach for ameliorating the symptoms of schizophrenia, in that it specifically targets particular types of receptors in neurons called muscarinic receptors. No previously available medication has done this, although a very effective treatment called clozapine does affect a wide range of receptors including muscarinic receptors.
“Clinical trials show that this medication does on average improve symptoms in people with schizophrenia. What we would expect is that some people will respond better than others. Since we cannot predict who will respond to which medication, it seems that this would be a treatment well worth trying in anybody who is not doing well on their current medication.
“It is important to note that, like other treatments for schizophrenia, this novel medication is associated with a number of side effects. Some of these are potentially severe and so this medication will not be an option for people who have particular health conditions.
“Overall, I think this treatment does offer psychiatrists a completely new way of trying to help people with schizophrenia and I would expect that there will be some patients who will derive considerable benefit from it.”
Dr Sameer Jauhar, Senior Clinical Lecturer in Affective Disorders and Psychosis, Consultant Psychiatrist, King’s College, London and South London and Maudsley NHS Foundation Trust, said:
“Schizophrenia can be a devastating illness for people and their families, and the effects on society are significant.
“We do have effective treatments, and the pharmacological treatments are a foundation for holistic care (which includes psychosocial interventions).
“Unfortunately currently available antipsychotics have significant side-effects, which include weight gain and movement effects, and this can affect peoples’ concordance with treatment.
“All currently licensed antipsychotics exert effects on the dopamine system, and this has been the case for at least 50 years.
“We have had false dawns before, despite significant efforts in the field (with significant financial investment) phase three trials of newer compounds have so far been disappointing.
“This novel treatment is the first of its kind, which does not act directly on the dopamine system, with good phase three trial data.
“The side effect profile from Phase three trials suggests it has less of the side effects noted with current treatments.
“It is acknowledged that these trials are short in duration, and we will need longer-term trials, to inform clinical care.
“In my opinion, as a clinician and researcher, this is possibly one of the most exciting developments in our field, and I am very excited about this.”
Dr Robert McCutcheon, Wellcome Clinical Research Career Development Fellow, Department of Psychiatry, University of Oxford, said:
Just how significant is this approval in the mental health/ schizophrenia treatment field?
“This is a major advance – it is the first treatment for schizophrenia with a novel target for 70 years.
Why do we need other drug treatments in schizophrenia?
“Current treatments are ineffective for many of the symptoms of schizophrenia, we need compounds with novel mechanisms of action.
What is different about this drug to previous drugs for schizophrenia?
“All other treatments work by targeting dopamine receptors. This is the first treatment that has a different target. We hope this may mean it can help people who don’t respond to standard treatments and maybe help the symptoms that aren’t helped by existing treatments.
What does this mean for patients in the UK who may be excited about this news?
“We will be running the first UK trial of this compound in Oxford, starting in 2025.”
Dr Paul Keedwell, Consultant Psychiatrist and Fellow of the Royal College of Psychiatrists, said:
“New candidates for the treatment of this frequently debilitating condition are always welcome. However, the clinical effectiveness needs to be tested in real clinical settings. We also need to know how well it is tolerated given its tendency to cause gastro-intestinal problems in some patients.”
Declared interests
Prof Oliver Howes: Dr Howes has received investigator-initiated research funding from and/or participated in advisory/ speaker meetings organised by Abbvie, Alkermes, Angellini, Autifony, Biogen, Boehringer-Ingelheim, Delix, Eli Lilly, Elysium, Heptares, Global Medical Education, Invicro, Jansenn, Karuna, Lundbeck, Merck, Neumora, Neurocrine, Ontrack/ Pangea, Otsuka, Sunovion, Teva, Recordati, Roche, Rovi and Viatris/ Mylan. He was previously a part-time employee of Lundbeck A/v. Dr Howes has a patent for the use of dopaminergic imaging.
Prof Matt Jones: No declarations of interest
Dr Lynsey Bilsland:
For more information about Cobenfy and Wellcome’s connection: https://wellcome.org/news/new-treatment-for-schizophrenia-Cobenfy
Dr Sameer Jauhar: SJ has given educational talks on psychosis for Behringer=Ingelheim, Sunovian, Janssen, and Lundbeck. He has consulted for LB Pharmaceuticals on antipsychotics. He is a co-investigator of a Wellcome funded grant examining the mechanisms of action of Kar-XT, and has received no funding from the drug company. He has sat on a Wellcome Funding Panel, and NICE Technology appraisal panel for treatment of antipsychotic induced movement disorder. He is a Council Member of the British Association for Psychopharmacology (unpaid) and Academic Faculty of the Royal College of Psychiatrists (unpaid).
Dr Robert McCutcheon: RAM has received speaker/consultancy fees from Boehringer Ingelheim, Janssen, Karuna, Lundbeck, Newron, Otsuka, and Viatris, and co-directs a company that designs digital resources to support treatment of mental ill health. I am leading a Wellcome trust funded RCT of the compound in early psychosis.
Dr Paul Keedwell: No conflict of interest.