The Latest in New and Emerging Therapies in Schizophrenia: Dr Megan Ehret

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

Ehret discussed schizophrenia management strategies in 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.

Transcript

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

Cobenfy is the newest medication, which is our first true new mechanism. In the past, we've had agents that maybe have different binding profiles or affinities for dopamine or serotonin. This is the first medication that is working on the muscarinic receptors. This particular medication is a combination of xanomeline and trospium.

Xanomeline is really what is thought to help with the psychosis. It is an M1 and M4 receptor agonist at both of those receptors, and it crosses the blood-brain barrier and works on both the M1 and M4 receptors. Now, because of the way that it works on those particular receptors, it lends itself to a lot of adverse effects in our periphery. So, the addition of the trospium, which doesn't cross the blood-brain barrier, is an antagonist at the M1 through M5 receptors, and it's an antimuscarinic. So, it's really controlling the adverse effects of the medication, so it doesn't help in schizophrenia at all. It's really there to help with some of the side effects that we get from the xanomeline.

I'm very excited about the potential new mechanism of this medication, and I think we still have a lot to learn about how we utilize this medication in the treatment of schizophrenia, but it is some groundbreaking work to have this brand-new mechanism available for our patients.

Are there other emerging therapies you're keeping an eye on?

In addition to Cobenfy, which is the first in this particular class, there are several other muscarinic agents that are currently being trialed. We have some other agents within this, and some of them will be different. They're not all M1 and M4 receptor agonists. We're really going to be learning a lot about the muscarinic receptors and specifically the differences between M1 and M4 as we move forward.

We have seen some failures. Most recently some of the TAAR1 partial agonists that we had a lot of hopes for.^2,3 Some of those have failed in their phase 3 trials. But we're also looking at some glycine transporters and some dead amino acid oxidase medications. I think there are some other classes of medications that I am very hopeful that we'll have some new potential mechanisms for the treatment of schizophrenia.

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

References

1. Grossi G. First schizophrenia treatment 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 schizophrenia 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 schizophrenia trial. BioSpace. May 23, 2023. Accessed October 14, 2024. https://www.biospace.com/roche-terminates-second-phase-ii-schizophrenia-trial