A new schizophrenia medication with a different way of working has been approved by the US Food and Drug Administration (FDA). Cobenfy, formerly known as KarXT, is a new type of antipsychotic showing promising results for people with schizophrenia and the treatment of their symptoms. Although it is waiting approval in Australia, it is hoped it will be available for patients within months.

We sat down with NeuRA Senior Research Scientist and Head of Preclinical NeuroPsychiatry, Dr Tertia Purves-Tyson, to find out how this new medication works and what it might mean for people with schizophrenia.

Can you explain how Cobenfy (formerly KarXT) works for schizophrenia?

Cobenfy is the first new pharmacological treatment with a new mechanism of action for schizophrenia in 70 years. This drug really could be a game changer for people with this debilitating illness. Cobenfy acts via activating receptors in the brain called muscarinic receptors. These receptors are reduced in the brains of people with schizophrenia, so Cobenfy works to increase the activity of these receptors.

What makes Cobenfy different to other treatments available for schizophrenia?

Cobenfy acts via a different neurobiological mechanism to currently available treatments. All current antipsychotic medications for schizophrenia block dopamine D2 receptors. Cobenfy is the first drug to be given approval for the treatment of schizophrenia that targets a different class of receptor, muscarinic receptors. Cobenfy works, not by blocking these receptors, but by activating them.

What have the trials found in terms of benefits for people using this new treatment?

In the clinical trials, Cobenfy reduced positive symptoms, such as psychosis, and negative symptoms, such as lack of motivation, decreased experience of pleasure, decreased desire for social contact.

In contrast to the general understanding of ​‘positive’ and ​‘negative’ as meaning good and bad, in schizophrenia research, ​‘positive symptoms’ actually refer to the addition of abnormal behaviours or experiences, like hallucinations and delusions, while ​‘negative symptoms’ refer to the absence or reduction of normal functions, such as lack of motivation or social withdrawal.

This is significant, as current D2 receptor-blocking antipsychotics essentially only reduce psychosis, but also have severe side effects. They are also only effective in about 60% of people with schizophrenia.

It’s also worth noting that secondary analyses in the clinical trials of Cobenfy (KarXT) also showed evidence that this new medication may improve cognitive problems in people with schizophrenia, although further evidence is needed to confirm this.

What are the potential side effects of Cobenfy?

Cobenfy was determined in the clinical trials to be generally well tolerated, but the most common side effects of Cobenfy in the trials were constipation, indigestion, nausea and vomiting. This is because the muscarinic system is involved in gut function and activating muscarinic receptors can cause gastrointenstinal side effects.

However, Cobenfy is a clever combination of two drugs — a muscarinic activator that enters the brain and improves schizophrenia symptoms, and a muscarinic blocker that does not enter the brain, but only acts in the body to prevent or reduce gastrointestinal side effects. So, although there can still be some gastrointestinal side effects from Codenfy, they are minimised by the combination of these two drugs.

Who will be the best candidates for Cobenfy treatment?

It is likely that some people will respond better than others to Cobenfy, but there is no way to predict this – research is needed to understand who will get the most benefit. However, there are some people with schizophrenia who do not get benefit from currently available antipsychotics, and Cobenfy is now an alternative option for these patients to try.

It is gratifying as a neuroscientist and researcher in schizophrenia to see a new drug come to market. From my perspective, it highlights the importance of basic research to understand molecular mechanisms that can lead to clinical benefit. It is a great reminder that new knowledge generated in the laboratory will eventually lead to better health outcomes for patients.