In September, the FDA approved the first new treatment for schizophrenia in decades.¹ Cobenfy (xanomeline and trospium chloride) has a novel mechanism of action and this drug shows great potential in treating patients with schizophrenia, said Megan Ehret, PharmD, MS, BCPP, professor and co-director of the Mental Health Program. of the University. of Maryland, School of Pharmacy.

Ehret discussed strategies for managing schizophrenia during a session last week at the Academy of Managed Care Pharmacy (AMCP) Nexus, held October 14-17 in Las Vegas, Nevada.

This transcript has been lightly edited for clarity.

Transcription

The FDA recently approved Cobenfy. What does this treatment do for patients with schizophrenia?

Cobenfy is the newest drug, our first truly new mechanism. In the past, we have had agents that may have different binding profiles or affinities for dopamine or serotonin. It is the first drug that acts on muscarinic receptors. This particular medication is a combination of xanomeline and trospium.

Xanomeline is definitely believed to help with psychosis. It is an agonist of the M1 and M4 receptors on these two receptors, it crosses the blood-brain barrier and acts on both the M1 and M4 receptors. Now, because of the way that this acts on these particular receptors, it lends itself to a lot of unwanted effects in our periphery. So the addition of trospium, which does not cross the blood-brain barrier, is an antagonist of M1 to M5 receptors, and it is an antimuscarinic. So it’s really about controlling the side effects of the drug, so it doesn’t help at all in the treatment of schizophrenia. It’s really there to alleviate some of the side effects that we get from xanomeline.

I’m very excited about the potential new mechanism of this drug, and I think we still have a lot to learn about how we use this drug in the treatment of schizophrenia, but it’s groundbreaking work to have this brand new mechanism. for our patients.

Are there any other emerging therapies that you are monitoring?

Besides Cobenfy, which is the first in this particular class, several other muscarinic agents are currently being tested. We have other agents in this framework, and some of them will be different. They are not all M1 and M4 receptor agonists. We’re really going to learn a lot about muscarinic receptors and specifically the differences between M1 and M4 as we move forward.

We have seen some failures. More recently, some of the TAAR1 partial agonists we had high hopes for.^2.3 Some of them failed in their phase 3 trials. But we are also studying some glycine transporters and some dead amino acid oxidase drugs. I believe there are other classes of drugs and I am hopeful that we will have potential new mechanisms for the treatment of schizophrenia.

I think what will be interesting as we move forward is whether these drugs are used in combination because we now have different mechanisms or whether patients respond better to one class over another.

References

1. Grossi G. The first treatment for schizophrenia approved in decades targets cholinergic receptors. AJMC®. September 27, 2024. Accessed October 14, 2024. https://www.ajmc.com/view/first-schizophrenia-treatment-approved-in-decades-targets-cholinergic-receptors

2. Goodwin K. Sumitomo, Otsuka’s schizophrenic candidate fails phase III trials. BioSpace. July 31, 2023. Accessed October 14, 2024. https://www.biospace.com/sumitomo-otsuka-s-schizophrenia-candidate-fails-phase-iii-trials

3. Goodwin K. Roche terminates second phase II study in schizophrenia. BioSpace. May 23, 2023. Accessed October 14, 2024. https://www.biospace.com/roche-terminates-second-phase-ii-schizophrenia-trial