Navigating The FDA Playbook For Psychedelic Therapies

Let's start with FDA's current posture towards psychedelics.

Stepping back, how would you characterize FDA's current view towards psychedelic therapies as more programs move into this late stage of development, particularly in light of that new guidance from last week?

Sure.

Great, and, you know, really try to tackle this question in two different directions.

It's kind of the bottom-up view at FDA and maybe the top-down view from the president on down into FDA.

From the bottom-up view, I think it's important to recognize that, you know, the recent executive orders and other actions coming out of the White House are entering, you know, an agency that I think has already shown a degree of excitement and enthusiasm for at least the potential, the potential of breakthrough medicines that might have significant impacts on mental health disorders.

A lot of these therapies that are coming through the pipeline now have breakthrough designations awarded by FDA as a signal of their enthusiasm, and those designations predate the Trump administration, go back several years.

I think if you listen to what, uh, FDA folks have said publicly, like Tiffany Farchione, who's the head of the psychiatric division that will review these therapies, they've spent their careers doing reviews of antidepressants where if you can find a 20% improvement on a rating scale i-in, like, two out of five trials, you're happy.

And now you're seeing at least reports of much more dramatic efficacy results in some pretty tough-to-treat conditions.

So I think the excitement level of the potential to feel there is very real.

And then, of course, uh, I think you can also look at the, the review of a psychedelic medicine a couple years ago for MDMA that ended negatively.

Obviously, that product was rejected.

But if you look at how FDA approached that review and the communication they did around it, I think they were going out of their way to say, "You know, there's problems with this application, but that doesn't mean we aren't excited about the potential if these therapies can show it in a rigorous way, what they can do," and that they will absolutely be ready to approve them if the efficacy is there and, and, you know, demonstrated in rigorous trials.

There's this top-down piece coming from the White House, Joe Rogan on a podcast and [chuckles] coming into the White House and doing executive orders, former Commissioner McCary as well.

That's kind of a double-edged sword.

The good news is you know if you're at FDA and you're, you're inclined to approve one of these medicines, the White House isn't gonna give you a hard time about it, quite the opposite.

But there is, if anything, a little danger that that sense of top-down push causes some pushback within the agency.

If there wasn't already, in my view, this kind of organic bottom-up receptivity, I'd be more worried about that.

But it is a factor to weigh as we think about this process.

I remember that Lycos Ad Com, and I remember the FDA pushback, correct me if I'm wrong, being more about, like, conduct, like protocol conduct, missing data, really things outside the norm, rather than FDA pushing back on the magnitude of efficacy or the meaningfulness of the data.

They were just more concerned about if they could trust it given the reporting issues.

Was that-

Exactly.

And, and I think they also did, both at the advisory committee and some follow-up communications, to really, really try to educate other sponsors about where the, the pitfalls were.

And I think if you were looking at it, if, if there was a belief within the agency that this whole class of medicines was ridiculous and this is hype and hysteria, I don't think they'd have gone to that extra effort to say, "Here's where we think you can do things differently and, and, you know, have a chance at success."

Let's start with FDA's current posture towards psychedelics.

Stepping back, how would you characterize FDA's current view towards psychedelic therapies as more programs move into this late stage of development, particularly in light of that new guidance from last week?

Sure.

Great, and, you know, really try to tackle this question in two different directions.

It's kind of the bottom-up view at FDA and maybe the top-down view from the president on down into FDA.

From the bottom-up view, I think it's important to recognize that, you know, the recent executive orders and other actions coming out of the White House are entering, you know, an agency that I think has already shown a degree of excitement and enthusiasm for at least the potential, the potential of breakthrough medicines that might have significant impacts on mental health disorders.

A lot of these therapies that are coming through the pipeline now have breakthrough designations awarded by FDA as a signal of their enthusiasm, and those designations predate the Trump administration, go back several years.

I think if you listen to what, uh, FDA folks have said publicly, like Tiffany Farchione, who's the head of the psychiatric division that will review these therapies, they've spent their careers doing reviews of antidepressants where if you can find a 20% improvement on a rating scale i-in, like, two out of five trials, you're happy.

And now you're seeing at least reports of much more dramatic efficacy results in some pretty tough-to-treat conditions.

So I think the excitement level of the potential to feel there is very real.

And then, of course, uh, I think you can also look at the, the review of a psychedelic medicine a couple years ago for MDMA that ended negatively.

Obviously, that product was rejected.

But if you look at how FDA approached that review and the communication they did around it, I think they were going out of their way to say, "You know, there's problems with this application, but that doesn't mean we aren't excited about the potential if these therapies can show it in a rigorous way, what they can do," and that they will absolutely be ready to approve them if the efficacy is there and, and, you know, demonstrated in rigorous trials.

There's this top-down piece coming from the White House, Joe Rogan on a podcast and [chuckles] coming into the White House and doing executive orders, former Commissioner McCary as well.

That's kind of a double-edged sword.

The good news is you know if you're at FDA and you're, you're inclined to approve one of these medicines, the White House isn't gonna give you a hard time about it, quite the opposite.

But there is, if anything, a little danger that that sense of top-down push causes some pushback within the agency.

If there wasn't already, in my view, this kind of organic bottom-up receptivity, I'd be more worried about that.

But it is a factor to weigh as we think about this process.

I remember that Lycos Ad Com, and I remember the FDA pushback, correct me if I'm wrong, being more about, like, conduct, like protocol conduct, missing data, really things outside the norm, rather than FDA pushing back on the magnitude of efficacy or the meaningfulness of the data.

They were just more concerned about if they could trust it given the reporting issues.

Was that-

Exactly.

And, and I think they also did, both at the advisory committee and some follow-up communications, to really, really try to educate other sponsors about where the, the pitfalls were.

And I think if you were looking at it, if, if there was a belief within the agency that this whole class of medicines was ridiculous and this is hype and hysteria, I don't think they'd have gone to that extra effort to say, "Here's where we think you can do things differently and, and, you know, have a chance at success."