Ep. 332 - Obesity in Focus. Plus: What’s Next for FDA

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<v Eric Pierce>BioCentury This Week is brought to you by Voyager Therapeutics.

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<v Jeff Cranmer>Pfizer has won the bidding war for Metsera.

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<v Jeff Cranmer>What can we learn from the week long wrangling between Pfizer and Novo for Metsera and what it means for cross-border M&A.

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<v Jeff Cranmer>Staying with obesity, a pair of amylin data sets made for an interesting ObesityWeek in Atlanta.

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<v Jeff Cranmer>Plus Jim Wilson, is rethinking the funding model for ultra rare therapies.

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<v Jeff Cranmer>P lus more leadership turmoil at FDA as Richard Pazdur declines the CDER job.

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<v Jeff Cranmer>But what's FDA going to look like moving forward?

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<v Jeff Cranmer>I'm Jeff Cranmer, and this is the BioCentury This Week podcast.

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<v Jeff Cranmer>Joining me are my colleagues.

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<v Simone Fishburn>Simon Fishburn, editor in chief.

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<v Stephen Hansen>Stephen Hansen, director of Biopharma Intelligence.

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<v Lauren Martz>Lauren Martz, executive Director of Biopharm Intelligence.

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<v Steve Usdin>And Steve Oden, Washington editor.

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<v Jeff Cranmer>All right, guys.

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<v Jeff Cranmer>Thanks for joining me.

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<v Jeff Cranmer>You all have quite different things to talk about, Stephen.

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<v Jeff Cranmer>I guess maybe you're glad that this, uh, week long, uh, bidding war is over.

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<v Jeff Cranmer>What, uh, where did the ball last bounce?

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<v Stephen Hansen>I think so it's been, uh, quite a wild week.

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<v Stephen Hansen>So just, I mean, if you heard last week's podcast, we talked about this fairly extensively, but, um, if you recall, Pfizer,  was set to acquire, Metsera in a deal they announced in late September.

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<v Stephen Hansen>Then, on October 30th, Novo came in with a bid, arrival bid to acquire Metsera and sort of the bidding war started from there.

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<v Stephen Hansen>in the intervening period we had Pfizer suing Novo and suing Metsera for breach of contract.

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<v Stephen Hansen>there was, talk about, America first and these sorts of things.

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<v Stephen Hansen>There's all this sort of drama that was happening in between, but kind of where it all landed was over the weekend.

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<v Stephen Hansen>Pfizer announced that it had, again, increased its bid for Metsera, to what amounted to,  7.6, billion dollars upfront, plus a CVR worth up to 2.4 billion.

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<v Stephen Hansen>So overall 10 billion, that basically equaled what Novo's final bid had been.

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<v Stephen Hansen>then Novo announced over the weekend that it was, uh, basically pulling out that it was no longer gonna offer any,  any new bids.

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<v Stephen Hansen>So kind of where things stand is now Pfizer Metsera are, now looking to go forward  for a$10 billion overall, acquisition price on Metsera rather than the roughly seven and a half is kind of where it stood, before Novo got involved.

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<v Stephen Hansen>So, quite the sweetened deal from, where things stood.

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<v Steve Usdin>I'm wondering how much you mentioned the America first thing, you know, I'm really curious, how much do you think that played into it?

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<v Steve Usdin>How much did the FTCs intervention in making it seem like the Novo bid was gonna be disadvantaged compared to Pfizer?

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<v Simone Fishburn>So let me answer

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<v Steve Usdin>was that.

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<v Simone Fishburn>The answer's a ton.

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<v Simone Fishburn>Okay, so Stephen and I have been talking about this.

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<v Simone Fishburn>I think it is not possible to look at this course of events.

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<v Simone Fishburn>We know they said that FTC basically called up Metsera and said this offer is questionable, Novo, even the offer of money upfront might get reversed.

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<v Simone Fishburn>I believe this was done while the government shut down was still on.

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<v Simone Fishburn>There's clearly a, a lot of FTC hand in this all I can say is, Lina Khan could have done this herself.

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<v Steve Usdin>So the, the, the question I guess that has going forward is, is, this one off?

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<v Steve Usdin>It seems, seems like these things are, are never one off.

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<v Steve Usdin>People always say they're gonna be one off, but I think that people are gonna have to think about this when you're talking about these kinds of deals.

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<v Steve Usdin>going forward for the remainder of this administration.

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<v Simone Fishburn>think I, sorry, Steven, I know you wanna come into this, but I wanna add to that.

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<v Simone Fishburn>I mean, there's that generally.

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<v Simone Fishburn>But that's what you are calling the America first thing, Steve.

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<v Simone Fishburn>But you know, you've got Bourla having cozied up to Trump.

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<v Simone Fishburn>But there's another part of this, which Steven maybe you can talk about, which is whether other obesity companies should be thinking, I'm not gonna be able to partner with Lilly or Novo.

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<v Stephen Hansen>Yeah.

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<v Stephen Hansen>So here's what I think  I think there was a clear argument that this would've breached the antitrust.

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<v Stephen Hansen>laws in the U.S. I mean, I think for one sense, I think that's exactly why Novo chose to pursue such a unique deal structure was because they probably knew this was gonna be hard, very hard to get through.

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<v Stephen Hansen>And so why they went after this, you know, very unique structure that would put so much money up front.

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<v Stephen Hansen>secondly, I mean, Novo itself reports that they, hold 48% of the market share for the GLP-1 market in the U.S. in diabetes.

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<v Stephen Hansen>And based on sales of Lilly's drugs, I'm pretty confident that we can say that Lilly probably holds another 48% in the U.S. And so when you look at,  definitions of dominant market position in antitrust, you know, legislation, I think this clearly fits.

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<v Stephen Hansen>You know, when you're talking about GLP-1s, I think Metsera and Novo kind of clearly fit into that dominant market position a rgument.

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<v Stephen Hansen>And so I, I actually think Pfizer had a pretty good case to say that this wasn't gonna make it by.

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<v Stephen Hansen>And so while I think it's very convenient that Novo was a Danish company, for Bourla, in terms of using that America first argument, I would argue that if you took Novo out and you inserted Lilly, I think the FTC would've had a similar approach here.

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<v Stephen Hansen>I don't think Lilly could have gotten t his deal done with Metsera, with the same deal structure.

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<v Stephen Hansen>I think the America first helped just from a optics kind of being able to like lean on them and maybe to get it done a little bit quicker.

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<v Stephen Hansen>But I, I think just from an antitrust perspective, I think both Lilly

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<v Simone Fishburn>Stephen, what about the,

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<v Stephen Hansen>would've had a hard time

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<v Simone Fishburn>What about the argument that I've read in the Journal and in my own Slack messages to you, about the number of other pharmas with activity in this space?

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<v Simone Fishburn>You've got Amgen and you can name them, and this is a molecule that's not yet on the market, so you know, it's.

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<v Stephen Hansen>yeah, that's true.

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<v Stephen Hansen>And, you know what, I think in five years time, you probably could easily make the argument that Novo could buy, a next gen GLP-1 and probably be in a position to do that because there would be four or five other GLP-1s out there and they wouldn't have as dominant a position.

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<v Stephen Hansen>But I think at this point in time.

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<v Stephen Hansen>you know, few conversations I've had with some M&A lawyers as well.

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<v Stephen Hansen>they think there's a pretty strong argument to say that as of right now, Novo has that dominant position, and therefore, when you're talking about GLP-1s, this would be a hard one to push forward with.

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<v Stephen Hansen>Doesn't mean to say they can't do deals elsewhere.

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<v Stephen Hansen>Like we've, we've seen the Lilly do and Novo obviously do due deal with obesity.

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<v Stephen Hansen>Novo bought, you know, CB1, inhibitor.

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<v Stephen Hansen>Which was, a different, molecule, different class.

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<v Stephen Hansen>Lilly's done deals for bimagrumab you know, which is sort of the, activin antibody So there are deals to be done.

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<v Stephen Hansen>I just think very narrowly in this GLP-1 class, this is one where it would be harder to forward from an antitrust position.

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<v Simone Fishburn>Okay.

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<v Simone Fishburn>Last thing then.

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<v Simone Fishburn>If they had this strong antitrust position, was sure of it and actually got that verified by Metsera in their announcement.

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<v Simone Fishburn>Why did they have to up the bid?

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<v Simone Fishburn>That's Pfizer.

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<v Simone Fishburn>Why did Pfizer up the bid?

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<v Stephen Hansen>I've been thinking about this since you originally put this to me earlier, I think the reason you upped the bid is because you take the decision out of Metsera's hands.

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<v Stephen Hansen>When you match Novo's offer and you have the clear runway from a regulatory perspective, there's no decision to be made by Metsera's board, it's clearly the better offer to take.

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<v Stephen Hansen>I think if you try to go in with a lower offer, you make it much harder on Metsera to decide.

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<v Stephen Hansen>And so I think, Pfizer's board was just finally like, you know what, whatever, just up the offer, make it an offer.

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<v Stephen Hansen>They can, you know, this is like the, the Godfather offer, make'em an offer They can't refuse.

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<v Stephen Hansen>And let's just move on with it.

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<v Simone Fishburn>Uh, all right.

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<v Simone Fishburn>So I think that we can agree that basically they listened to our podcast last week and decided what's another billion between friends.

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<v Simone Fishburn>And I also agree with you that from Metsera's point of view, it makes complete sense.

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<v Stephen Hansen>that's right.

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<v Jeff Cranmer>All righty.

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<v Jeff Cranmer>Thanks for that, Stephen.

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<v Jeff Cranmer>You were, uh, certainly on top of that.

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<v Jeff Cranmer>we didn't get you outta bed for anything, but, uh, you sort of waited to make your next story, make your next move.

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<v Jeff Cranmer>Okay.

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<v Jeff Cranmer>Well, Lilly sat on the sidelines of the Metsera madness, but it was making its mark in Hotlanta.

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<v Jeff Cranmer>For ObesityWeek, which wrapped up on Friday.

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<v Jeff Cranmer>SITC fans, we know you're out there, we'll get to you next week.

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<v Jeff Cranmer>but we're gonna stay with the obesity theme here.

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<v Jeff Cranmer>Lilly, set the bar for amylin with weight loss data, but we also saw two data sets that called into question the quality of weight loss, and how folks were thinking about it for amylin.

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<v Jeff Cranmer>Stephen, break this down for us.

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<v Stephen Hansen>Yeah, sure.

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<v Stephen Hansen>Thanks Jeff.

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<v Stephen Hansen>So the, as you mentioned, so this past week was ObesityWeek and for those that aren't, I guess, big on nightclubs and things in Atlanta, Georgia.

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<v Stephen Hansen>and yeah, I mean, I guess the most impressive data out of the conference from my perspective, was the eloralintide, data from Lilly.

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<v Stephen Hansen>It is an amylin receptor biased, agonist.

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<v Stephen Hansen>and it was pretty impressive.

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<v Stephen Hansen>So this was 48 week data.

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<v Stephen Hansen>we already kind of knew this, that this molecule was pretty good because at ADA earlier this year, we saw 12 week data that showed 11.5% weight loss.

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<v Stephen Hansen>and now the 48 week data showed nearly 20% placebo adjusted weight loss.

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<v Stephen Hansen>I mean, that's pretty much on par with Lilly's Tirzepatide, so.

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<v Stephen Hansen>Very impressive data.

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<v Stephen Hansen>and then on, on the safety side, I mean, across all the doses, it looked better than what we would typically see with an incretin.

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<v Stephen Hansen>But then when they had a, um, a titration cohort that showed weight loss of it to 16%, I mean, the, the, the GI side effects were very mild, just, A few percentage points above what they were seeing with placebo.

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<v Stephen Hansen>So it was a very promising sort of profile for, um, that program.

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<v Stephen Hansen>To get what you were saying, Jeff, about the weight loss quality, so people had previously, you know, been telling me that amylin monotherapy could reach kind of the high teens in terms of weight loss, but I was always kind of skeptical of that.

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<v Stephen Hansen>that was primarily because.

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<v Stephen Hansen>Everyone had been talking about this preclinical data that they'd seen for amylin and how that, weight loss was predominantly driven by fat mass loss and that it was a muscle sparing mechanism and all these things, and sort of by definition, if you're only losing weight from fat and not other parts of lean mass, well it is just harder to lose more than what you would typically see with the GLP-1.

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<v Stephen Hansen>So I was always quite skeptical of the idea that you could get kind of GLP-1 like weight loss from an amylin monotherapy.

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<v Stephen Hansen>Now we know why we can see the size of weight loss is because, we got data for CagriSema from their, REDEFINE 1 Phase III study where they also have Cagrilintide and Semaglutide, monotherapy arms.

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<v Stephen Hansen>And when they looked at body composition, essentially there was no difference in weight loss between the amylin and the GLP-1 actually in that trial.

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<v Stephen Hansen>There was a bit more weight loss from fat for Semaglutide than there was from the amylin arm of that study.

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<v Stephen Hansen>And then on top of that, for the eloralintide data, they also had a body composition, subset of the data.

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<v Stephen Hansen>And that also showed basically weight loss where you get 60 to 70% weight loss from fat, and then around 30 to 40% from lean mass, which again, is basically what we would expect to see from an incretin based therapy.

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<v Stephen Hansen>So.

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<v Stephen Hansen>It's essentially two fairly, sizable knocks against amylin being a muscle sparing, mechanism, which was one of the potential benefits of this class in terms of it being able to, you know, be a core, obesity therapy going forward.

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<v Stephen Hansen>So right now, the way I would think about it is, unless we see data, otherwise, I'm sort of, in my mind, I'm kind of removing that muscle sparing benefit from amylin.

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<v Stephen Hansen>I mean, the rest of the data still looks great.

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<v Stephen Hansen>It still is, GLP-1 like weight loss with better side effect profile.

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<v Stephen Hansen>I think there's still a real role for amylin to play as a core obesity treatment.

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<v Stephen Hansen>But, as of right now, I think we have to cut out the, uh, the muscle sparing mechanism.

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<v Jeff Cranmer>Well, thanks for the update, Stephen.

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<v Jeff Cranmer>What's next for you?

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<v Jeff Cranmer>What are you watching for?

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<v Stephen Hansen>Well, we're gonna have a look at, uh, there was some NLRP3 data in obesity recently, so I'm gonna have a take a bit of a deeper dive into that and kind of where things stand and then, uh, who knows?

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<v Stephen Hansen>I'm sure there's plenty of directions that, we can go from there.

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<v Stephen Hansen>So,

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<v Jeff Cranmer>thanks for that, Stephen.

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<v Jeff Cranmer>I'm looking forward to that piece for sure.

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<v Jeff Cranmer>All right.

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<v Jeff Cranmer>Enjoy your evening, suspect it's dinner time for you right now.

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<v Jeff Cranmer>Well, let's turn to Lauren.

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<v Jeff Cranmer>Lauren, had the pleasure of speaking to Jim Wilson recently, and,  she wrote, about what he has been up to since he left Penn. And, you know, she found FDA, has been trying to find ways to ease the regulatory path for ultra rare disease drugs, VCs, uh, not, not really taking the bait just yet.

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<v Jeff Cranmer>largely uninterested in the space.

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<v Jeff Cranmer>And so that sort of set the stage for,  Jim Wilson as he set out to develop and fund gene therapies for ultra orphan indications.

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<v Jeff Cranmer>Little more than a year in, uh, the hurdles he encountered, prompted him to,  rethink the funding model to keep his mission alive.

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<v Jeff Cranmer>Lauren, what did you learn?

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<v Lauren Martz>Yeah, thanks Jeff.

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<v Lauren Martz>So a few weeks ago we learned that Jim Wilson, who left his longstanding position at Penn to found Gemma Therapeutics, was launching a new company focused on AAV gene therapies for ultra rare diseases called Rare Therapeutics.

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<v Lauren Martz>So ultra rare diseases, were really at the center of the mission of Gemma, which launched a year ago when he left Penn.

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<v Lauren Martz>I spoke with Jim Wilson about, you know, why he was launching this new company that was focused on what I thought the original company was focused on, and he was very transparent, as you said.

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<v Lauren Martz>There was a lack of interest from the VCs that,  he approached in funding the ultra orphan, programs that he was trying to develop.

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<v Lauren Martz>So the whole idea behind Gemma was that the company would license later stage gene therapies for ultra orphan diseases that wouldn't require very much investment to get to the first approvals, then The company would use the Priority Review Vouchers and whatever sales were generated to fund future programs.

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<v Lauren Martz>You know, this did require some VC funding, especially at the beginning.

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<v Lauren Martz>And, interest from VC simply wasn't there.

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<v Lauren Martz>that's, of course something that we've been observing when we've been talking about gene therapy development over the course of this year and many years before that, you know, interest in gene therapy in general is declining for various reasons.

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<v Lauren Martz>Um.

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<v Lauren Martz>There just isn't really a line of sight to how to make these types of therapies for the rarest diseases, something that, that people think can be very profitable.

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<v Lauren Martz>The outcome is that Gemma Therapeutics is sticking with its earlier stage programs for the less rare, rare diseases in order to get VC backing.

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<v Lauren Martz>And then the ultra rare programs were spun out into this new company, Rare Therapeutics.

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<v Steve Usdin>How much of this is a consequence of the of sun setting, of the Priority Review Voucher, and how important would it be if the Priority Review Voucher came back?

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<v Lauren Martz>So that was a core part of the original model.

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<v Lauren Martz>you know, there is this expectation that those programs when approved would get Priority Review Vouchers that was just built into the funding model.

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<v Lauren Martz>And so without that, I think that that is a big component to why this may not have worked.

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<v Lauren Martz>developing these ultra rare programs really does depend on the government, the FDA regulatory incentive.

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<v Lauren Martz>So there were the Priority Review Vouchers, which, you know, we still have vouchers.

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<v Lauren Martz>They're not as predictable.

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<v Lauren Martz>They're not gonna be or they may not be for these, these types of indications as we've seen

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<v Steve Usdin>they're, and they, they're, they call 'em vouchers.

00:16:25.985 --> 00:16:29.554
<v Steve Usdin>They're not vouchers because they can't be transferred, they can't be sold.

00:16:29.587 --> 00:16:38.263
<v Steve Usdin>The, the key thing about the Priority Review Voucher wasn't that it sped up the development program, which is what the new Commissioner National Priority Voucher is supposed to do.

00:16:38.263 --> 00:16:42.735
<v Steve Usdin>The key thing about that was that they were, um, you know, Willy Wonka's magic ticket.

00:16:42.735 --> 00:16:48.340
<v Steve Usdin>You, you could, transfer them or you could sell them, for, you know, north of a hundred million dollars usually.

00:16:48.740 --> 00:16:51.610
<v Steve Usdin>that's a powerful incentive for developing these kinds of drugs.

00:16:51.909 --> 00:16:57.548
<v Steve Usdin>In the absence of that, it's gonna be a struggle to see how companies are gonna be able to come up with the investment to do it.

00:16:58.350 --> 00:16:58.817
<v Lauren Martz>Exactly.

00:16:58.817 --> 00:17:00.686
<v Lauren Martz>I think this is a demonstration of that.

00:17:00.952 --> 00:17:05.557
<v Lauren Martz>And I think there are sort of other incentives that this was depending on.

00:17:05.557 --> 00:17:13.298
<v Lauren Martz>So there's also this platform technology designation, which we have been seeing rollouts.

00:17:13.298 --> 00:17:17.970
<v Lauren Martz>You know, there have been two companies at this point that have received this designation, but.

00:17:18.770 --> 00:17:20.305
<v Lauren Martz>Again, that's something that's unpredictable.

00:17:20.305 --> 00:17:28.881
<v Lauren Martz>So the idea there is that if you have a therapy approved based on an underlying platform technology here, it would be the same AAV vector.

00:17:29.213 --> 00:17:35.953
<v Lauren Martz>There would be fewer requirements, fewer, as you know, you don't have to repeat some of the requirements, and that would streamline development and cut the costs.

00:17:35.953 --> 00:17:42.394
<v Lauren Martz>And so again, that's something, there's not a ton of certainty around when that can be available and if it will be available.

00:17:42.728 --> 00:17:50.402
<v Lauren Martz>When I spoke with Jim Wilson, he also cited some potentially more reliable incentives.

00:17:50.402 --> 00:17:58.576
<v Lauren Martz>There's the Rare Disease Evidence Principles Program, which is focused specifically on the ultra rare diseases, and that's where Rare Therapeutics is focused.

00:17:58.576 --> 00:18:10.823
<v Lauren Martz>So I think this is a story that we'll continue to follow as an example of how regulatory incentives can impact development of gene therapies for rare and ultra rare diseases.

00:18:11.656 --> 00:18:17.996
<v Steve Usdin>And we're also gonna be seeing the plausible mechanism pathway, at least that's what it's been called to date.

00:18:18.029 --> 00:18:22.701
<v Steve Usdin>Some kind of a, a new pathway that FDA is creating for ultra.

00:18:22.701 --> 00:18:27.873
<v Steve Usdin>Rare diseases that's gonna be announced, I think, uh, probably this week, but if not this week, then next week.

00:18:28.773 --> 00:18:30.541
<v Jeff Cranmer>Okay, thanks for that, Lauren.

00:18:30.709 --> 00:18:46.657
<v Jeff Cranmer>Lauren, specializes in covering, gene therapy new modalities, and she'll stay on top of this space for us, and you can read her piece at biocenturypodcast.com and I'll drop a link to the show notes.

00:18:46.657 --> 00:18:47.925
<v Jeff Cranmer>And speaking of.

00:18:48.527 --> 00:18:51.596
<v Jeff Cranmer>The show notes while you're, uh, checking those out.

00:18:51.596 --> 00:18:59.137
<v Jeff Cranmer>Uh, don't forget to like and subscribe BioCentury This W eek and check out our sister podcast, The BioCentury Show.

00:18:59.137 --> 00:19:01.906
<v Jeff Cranmer>Steve, you, uh, are looking very dapper today.

00:19:01.906 --> 00:19:03.674
<v Jeff Cranmer>You've got a green screen behind you.

00:19:03.674 --> 00:19:05.344
<v Jeff Cranmer>What's, what's on your agenda?

00:19:05.943 --> 00:19:10.781
<v Steve Usdin>yeah, I, I dressed up just for the podcast so people can hear me, uh, what I I sound like in a suit.

00:19:11.048 --> 00:19:19.223
<v Steve Usdin>No, I, I'm going to be doing an interview later this afternoon with, former NIH director and former Head of R&D at Sanofi, Elias Zerhouni.

00:19:19.724 --> 00:19:20.125
<v Jeff Cranmer>Alright.

00:19:20.125 --> 00:19:20.992
<v Jeff Cranmer>I'm looking forward to that.

00:19:20.992 --> 00:19:27.098
<v Jeff Cranmer>Yes, Simone did, uh, announce a new editorial policy where one of us has to wear a suit.

00:19:27.465 --> 00:19:28.099
<v Jeff Cranmer>every day.

00:19:28.200 --> 00:19:28.866
<v Jeff Cranmer>So, uh,

00:19:29.067 --> 00:19:30.568
<v Simone Fishburn>to see how this plays out, you know?

00:19:31.236 --> 00:19:32.136
<v Jeff Cranmer>yeah, me, me too.

00:19:32.136 --> 00:19:34.306
<v Jeff Cranmer>I mean, today, Eagles attire.

00:19:34.338 --> 00:19:36.174
<v Jeff Cranmer>Big, big Monday night game.

00:19:36.240 --> 00:19:42.346
<v Jeff Cranmer>But, uh, hey, we're gonna get back to Steve and what's happening in Washington, right after this.

00:19:42.980 --> 00:19:47.653
<v Alanna Farro>BioCentury This Week is brought to you by The 5th East-West Biopharma Summit in South Korea.

00:19:51.056 --> 00:19:58.497
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00:20:31.028 --> 00:20:37.102
<v Jeff Cranmer>And I have already begun recruiting, presenting companies for the East-West Summit.

00:20:37.102 --> 00:20:40.005
<v Jeff Cranmer>You can register now, to be a delegate.

00:20:40.204 --> 00:20:42.540
<v Jeff Cranmer>take advantage of that early bird rate.

00:20:42.540 --> 00:20:46.944
<v Jeff Cranmer>You'll wanna lock in your schedule once JP Morgan happens.

00:20:47.346 --> 00:20:48.512
<v Jeff Cranmer>we know how that is.

00:20:48.846 --> 00:20:50.414
<v Jeff Cranmer>it's, uh, hold onto your hats.

00:20:50.414 --> 00:21:11.269
<v Jeff Cranmer>Alright, uh, Steve, FDA Commissioner, Marty Makary, as you reported last week, had asked Richard Pazdur to serve as CDER director in the wake of George Tidmarsh's we talked about on that on last week's pod, so we won't need to dwell on the things around that, but you can check out last week's pod, get caught up.

00:21:11.435 --> 00:21:14.006
<v Jeff Cranmer>What is going on with leadership at FDA right now?

00:21:15.207 --> 00:21:17.675
<v Steve Usdin>Well, so here's what we know when we're talking about CDER.

00:21:17.976 --> 00:21:18.143
<v Steve Usdin>Um.

00:21:18.143 --> 00:21:22.013
<v Steve Usdin>We know, and you know, as I mentioned last week of George Tidmarsh is not coming back.

00:21:22.314 --> 00:21:31.256
<v Steve Usdin>Yeah, FDA Commissioner Makary asked Oncology Center of Excellence Director Richard HHS Secretary Robert F. Kennedy Jr., interviewed Pazdur.

00:21:31.556 --> 00:21:34.826
<v Steve Usdin>And I think it's important to point out that this is unprecedented.

00:21:34.826 --> 00:21:39.364
<v Steve Usdin>It's unprecedented for an HHS secretary to vet an FDA center director.

00:21:39.631 --> 00:21:43.868
<v Steve Usdin>But here's what I think, I think the job of the center director has become politicized.

00:21:44.201 --> 00:21:50.107
<v Steve Usdin>In the best of times, it's a really difficult job, and in the current administration it has become much more difficult.

00:21:50.107 --> 00:21:54.313
<v Steve Usdin>Whoever takes the position will have to be aligned with Kennedy's MAHA movement.

00:21:54.680 --> 00:22:02.753
<v Steve Usdin>They're gonna have to be willing to accept political interference and routine regulatory decisions, and they're gonna have to understand that they may not last longer than the current administration.

00:22:03.020 --> 00:22:09.493
<v Steve Usdin>Previous CDER directors and CBER directors have had the confidence that since they're civil servants, that they will.

00:22:09.760 --> 00:22:12.130
<v Steve Usdin>stay in the position for, a lengthy period of time.

00:22:12.396 --> 00:22:22.340
<v Steve Usdin>I'm not convinced that that's the case now, and whoever comes into the job is gonna have to deal with plummeting morale, depleted staffing, and kind of toxic pandemic politics.

00:22:22.340 --> 00:22:34.086
<v Steve Usdin>So it's gonna be tough to find somebody, to do the job who will do it with the same kind of, expertise and same kind of excellence as, previous CDER e directors have done it.

00:22:34.419 --> 00:22:42.059
<v Steve Usdin>And you can't really emphasize how important for the biopharm industry and for patients, the CDER director role is.

00:22:42.227 --> 00:22:45.497
<v Steve Usdin>in many ways it's more important than the FDA Commissioner

00:22:46.230 --> 00:22:50.634
<v Simone Fishburn>So Steve, Obviously there was Janet Woodcock for a very long time.

00:22:50.868 --> 00:22:55.173
<v Simone Fishburn>Then Patrizia Cavazzoni Janet was there for so long, Dr.

00:22:55.173 --> 00:23:01.846
<v Simone Fishburn>Woodcock, that I'm not actually sure to be honest, Steve, I don't remember who was before her, I'm sort of wondering whether there isn't scope.

00:23:01.846 --> 00:23:17.863
<v Simone Fishburn>I mean, if there were somebody good and competent, is there not scope for somebody to think, I, I have to survive one year, two year, three years, and this, how, how much does somebody think about just survival in a role like that versus walking in with an agenda?

00:23:17.863 --> 00:23:20.265
<v Simone Fishburn>I'm really gonna do, you know, big things.

00:23:20.499 --> 00:23:27.672
<v Simone Fishburn>think that's one of my concerns is the risk aversion that people at FDA will have, despite many things that.

00:23:27.939 --> 00:23:36.515
<v Simone Fishburn>Makary is talking about in terms of making drug development easier, there seems to be a concern about sticking your head out.

00:23:37.281 --> 00:23:37.481
<v Steve Usdin>Yeah.

00:23:37.481 --> 00:23:48.259
<v Steve Usdin>So look, I think that whoever comes into this position is gonna have to come into the position realizing, all the things that I mentioned earlier and, um, they're gonna have to be comfortable with that.

00:23:48.259 --> 00:24:10.281
<v Steve Usdin>They're gonna have to be, it's gonna have to be somebody who's comfortable in a more politicized environment, in an environment where the HHS secretary can decide that Tylenol, is no longer safe for, pregnant women or for, children, without any kind of process around it that is, is normal or that leucovorin is, uh, is an effective treatment for, autism.

00:24:10.749 --> 00:24:12.349
<v Steve Usdin>There's gonna be more and more of those things.

00:24:12.349 --> 00:24:14.486
<v Steve Usdin>So whoever comes into the position is gonna have to be.

00:24:15.119 --> 00:24:17.455
<v Steve Usdin>Comfortable dealing with, that environment?

00:24:17.823 --> 00:24:18.522
<v Steve Usdin>What does that mean?

00:24:18.522 --> 00:24:18.957
<v Steve Usdin>Yeah.

00:24:19.057 --> 00:24:28.133
<v Steve Usdin>One of the things that we're going to see, regardless of who's the CDER director going forward is, we're gonna see, more risk aversion.

00:24:28.432 --> 00:24:34.573
<v Steve Usdin>we're going to see less predictability, and we're gonna see more erratic decision making.

00:24:34.940 --> 00:24:38.442
<v Steve Usdin>And by erratic decision making, I mean decisions that are made.

00:24:38.844 --> 00:24:43.548
<v Steve Usdin>Then there's political blowback and FDA changing its mind.

00:24:43.548 --> 00:24:48.953
<v Steve Usdin>There have been several instances of that already in this administration, and I think, we're going to see more.

00:24:48.953 --> 00:24:54.659
<v Steve Usdin>There's quite a bit of concern about some of the complete response letters that have been issued in recent weeks and months.

00:24:55.160 --> 00:25:11.409
<v Steve Usdin>The patient groups and the companies and the investors are organizing political responses to try to pressure, FDA to reverse the complete responses or to define paths forward, to get those, some of those drugs out to patients.

00:25:11.710 --> 00:25:14.112
<v Steve Usdin>So I think that's the kind of thing that we're gonna see.

00:25:14.112 --> 00:25:20.684
<v Steve Usdin>And you know, as I, I wrote this big piece last week, kind of trying to look forward at what FDA is going to be like in the future.

00:25:21.118 --> 00:25:31.829
<v Steve Usdin>And those were some of the themes, you know, risk aversion, erratic decision making, less predictability at the same time, There's, a really, dedicated staff there.

00:25:32.063 --> 00:25:39.069
<v Steve Usdin>in many cases, people who have been there for a decade or more who are going to do their utmost to keep the ship.

00:25:39.770 --> 00:25:43.040
<v Steve Usdin>You know, going to keep the ship afloat and, and, and going in the right direction.

00:25:43.375 --> 00:25:57.923
<v Steve Usdin>So there are gonna be a lot of things that are gonna happen, um, relationships and, um, interactions, engagements between companies, sponsors and FDA that are going to move forward just as they should and as they have in the past.

00:25:58.123 --> 00:26:04.663
<v Steve Usdin>The problem, I think, among other problems is that it's unpredictable when things will, blow off course.

00:26:04.663 --> 00:26:05.329
<v Steve Usdin>You know, everything.

00:26:05.497 --> 00:26:08.599
<v Steve Usdin>It's gonna be going along just as you expect.

00:26:08.967 --> 00:26:13.471
<v Steve Usdin>And then for some reason, things aren't going along the way that you expect anymore.

00:26:13.704 --> 00:26:15.472
<v Steve Usdin>that's gotta be in the back of, everybody's mind.

00:26:16.907 --> 00:26:18.910
<v Jeff Cranmer>Alright, thanks for that update, Steve.

00:26:18.977 --> 00:26:22.012
<v Jeff Cranmer>yeah, definitely, uh, much gratitude to those people.

00:26:22.146 --> 00:26:27.852
<v Jeff Cranmer>keeping the light on moving, applications, giving companies advice.

00:26:28.086 --> 00:26:28.553
<v Jeff Cranmer>we need it.

00:26:28.819 --> 00:26:30.622
<v Jeff Cranmer>for those of you doing that, hang in there.

00:26:31.256 --> 00:26:31.823
<v Jeff Cranmer>Okay.

00:26:31.823 --> 00:26:37.729
<v Jeff Cranmer>Well, don't forget to turn into The BioCentury Show this week.

00:26:37.929 --> 00:26:42.500
<v Jeff Cranmer>we'll also have another special pod for you, Simone and Josh.

00:26:43.201 --> 00:26:51.509
<v Jeff Cranmer>we're up in Boston at the Venture Café Cambridge last week, a really good podcast focused on, all things Korea.

00:26:51.776 --> 00:26:56.013
<v Jeff Cranmer>one can only hope that Josh has finally seen, K-pop demon hunters.

00:26:56.013 --> 00:26:59.351
<v Jeff Cranmer>I know Simone, uh, lives it basically.

00:26:59.483 --> 00:26:59.884
<v Jeff Cranmer>So.

00:27:00.317 --> 00:27:01.385
<v Jeff Cranmer>on my to-do list.

00:27:01.419 --> 00:27:02.554
<v Jeff Cranmer>It is on my to-do list.

00:27:02.586 --> 00:27:06.958
<v Jeff Cranmer>I have to tell you, my husband cannot believe it is on my to-do list, but it is.

00:27:07.759 --> 00:27:10.561
<v Jeff Cranmer>Just as soon as I finish Shogun, I gotta finish Shogun, first.

00:27:10.694 --> 00:27:11.596
<v Jeff Cranmer>Oh, yeah.

00:27:11.596 --> 00:27:11.829
<v Jeff Cranmer>Yeah.

00:27:11.829 --> 00:27:11.895
<v Jeff Cranmer>I

00:27:11.930 --> 00:27:12.230
<v Simone Fishburn>Yeah.

00:27:12.663 --> 00:27:12.931
<v Simone Fishburn>Yeah.

00:27:13.597 --> 00:27:13.964
<v Jeff Cranmer>Yeah.

00:27:13.999 --> 00:27:14.531
<v Jeff Cranmer>All right.

00:27:15.133 --> 00:27:15.532
<v Jeff Cranmer>All right.

00:27:15.532 --> 00:27:20.939
<v Jeff Cranmer>Well, you got some plane rides ahead of you, so hopefully you can make some, uh, some headway on both fronts.

00:27:21.205 --> 00:27:21.839
<v Jeff Cranmer>Okay.

00:27:22.007 --> 00:27:23.008
<v Jeff Cranmer>thanks for tuning in.

00:27:23.008 --> 00:27:26.744
<v Jeff Cranmer>We will catch you for our regular pod, next week.

00:27:26.978 --> 00:27:32.017
<v Jeff Cranmer>Kendall Square Orchestra provides the music for BioCentury's Podcasts.

00:27:32.217 --> 00:27:35.920
<v Jeff Cranmer>Tickets are now on sale for the Group's eighth season.

00:27:35.920 --> 00:27:47.198
<v Jeff Cranmer>The group connects science and technology professionals and other members of the Greater Boston community to collaborate innovate and Inspire through music, while supporting causes related to healthcare and education.

00:27:48.732 --> 00:27:54.038
<v Eric Pierce>BioCentury would like to thank Voyager Therapeutics for supporting the BioCentury This Week podcast.

00:27:54.372 --> 00:28:02.279
<v Eric Pierce>To learn more about Voyager's programs advancing transformative medicines for neurological diseases, visit voyagertherapeutics.com.