When the Next Big Thing Falls Short

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

Dr. Allan M. Block

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.