Ep. 374 - Parkinson's deep dive & FDA trial reforms

New Parkinson’s disease programs aim to move beyond the historical norm of symptom management, branching into targeted therapeutics and cell therapies. On the latest BioCentury This Week podcast, BioCentury’s analysts review the most promising targets and trends shaping the Parkinson’s treatment landscape.
The team then turns to AstraZeneca’s build-out of its obesity portfolio, followed by FDA’s Operation TrialBlazer and what the reforms mean for reducing the time to launch a clinical trial in the U.S. — and whether they can help close the gap with China.
Finally, the analysts review recent FDA reversals of controversial regulatory decisions made under former Commissioner Marty Makary’s leadership and whether companies and investors can expect this reversion to the mean to carry forward.

View full story: https://www.biocentury.com/article/659958

#ParkinsonsDisease #ObesityDrugDevelopment #FDA #ClinicalTrials #DrugDevelopment

00:00 - Introduction
01:40 - Parkinson's New Targets
11:43 - AstraZeneca's Obesity Pipeline
18:37 - FDA's Operation TrialBlazer
27:33 - FDA Leadership Outlook

To submit a question to BioCentury’s editors, email the BioCentury This Week team at podcasts@biocentury.com.

Transcript

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[Auto-generated Transcript]

Stephen Hansen: 0:02

A deep dive analysis shows new targets and cell therapies for Parkinson's disease that go beyond symptom control. Plus, AstraZeneca's build-out in obesity, and FDA is hoping that a package of reforms can cut the time required to launch a clinical trial in the US. But will it meaningfully close the gap with China? The agency also appears to be unwinding regulatory barriers established under former Commissioner Marty Makary's leadership. I'm Stephen Hansen, co-host of the BioCentury This Week podcast, and joining me today is our Washington editor, Steve Usdin, our VP and editor-in-chief, Simone Fishburn, and, our biopharma analyst, Lindsay Martin. As you'll clearly recognize, our normal host, Jeff Cranmer, is not here this week. I believe he's off on a beach somewhere uh sipping on, what I'm guessing are probably mai tais maybe. I don't know. Simone, what do you think Jeff's preferred cocktail is for getting sunburned?

Simone Fishburn: 0:57

I think Jeff just drinks whiskey all times of day actually.

Stephen Hansen: 1:02

Regardless of location? You think even on a beach he'll, uh…

Simone Fishburn: 1:05

Yeah, you know, truth isn't subject to geography, so, you know

Stephen Hansen: 1:09

I think maybe that should be the trivia question for next week. We can, we can all guess what is, what is Jeff's favorite beach cocktail? well at least there I've already, already generated a bit of content for Jeff in a, in a teaser for him when he returns. But um you know, in the meantime… sorry, did you have a guess, Steve? Did you wanna guess what you think Jeff's uh preferred beach cocktail is?

Steve Usdin: 1:28

No, I think I, I, I've seen him drink a lot of different cocktails

Stephen Hansen: 1:35

All right.

Simone Fishburn: 1:35

Could be a paper plane, actually. I know he likes that. Anyway, let's get going

Stephen Hansen: 1:38

There we go. Let's get going. So we're gonna start off, Lindsay. welcome back to the podcast. Uh, great to have you joining us again.

Lindsay Martin: 1:45

Thanks, Stephen

Stephen Hansen: 1:46

you've dug deep into an analysis of the landscape of therapies and development for Parkinson's and kinda how they're moving beyond this historical focus on symptom control. but before we did dive in, you know, I did wanna ask you whether you came across a favorite new target or genetic variant while putting this together. Was there, is there one name that really, you know, stuck out to you as being your favorite?

Lindsay Martin: 2:06

Yeah, I, I think I do have a favorite. maybe, maybe I'm biased, but, there are like over forty new targets or potential first-in-class targets in the clinic right now. A handful of these are genetic targets, targeting factors that are rooted in genetic variants that may cause overactivation of kinases and, and things like that that lead to accumulation or aggregation of alpha-synuclein, which is really the key driver of Parkinson's disease, is having these excess misfolded toxic proteins. But I think the one that really stood out to me was LRRK2. And this kinase has had a bit of a, a troubled past, I guess you could say, in that this month it has seen another failure in May, Biogen and Denali announced a Phase IIb miss for LRRK2 in their LUMA study. But this study included Parkinson's all-comers, so not just patients with the genetic variant. And I think the target still holds out hope in that there are still patients that this target could really work for potentially. and some of the other companies that are pursuing this target are pursuing ways to enrich the target population or the patient population to better achieve sufficient targeting. And I think that some of those strategies might play out

Simone Fishburn: 3:30

So Lindsay um break this down a little bit because LRRK2, also a good name, L-R-R-K-2, has been around in Parkinson's for a while, and you know, obviously because we've got clinical data coming out. So just sort of for those who are not in the field or refreshers maybe for those who are peripheral in the field, explain how this kinase works and how that relates to the pathology. I think it's still not clear to me why it's taken until now. Like, what's gone wrong and what's different now? Is it like a segmenting of the population that is the reason you're still bullish? You're, you're still buying LRRK2, as it were, in terms of your, your target stock picks

Lindsay Martin: 4:11

Yeah, yeah. I think so the t-the target itself is a kinase. well, it really has three functions, but the main function of the protein is its kinase function, and that leads to… or patients that have LRRK2 genetic variants end up having overactive kinase signaling. And this leads to excess phosphorylation of the kinase's downstream target, which is Rab GTPases. And then this impairs the brain's ability to clear waste, and, and that itself can lead to accumulation of the alpha-synuclein and, like, toxic aggregation. So having this genetic variant really just predisposes the patients to having an inability to clear waste in the brain, and that leads to the downstream effects. Really the thing now is having patient stratification will be a key in order to see a difference, right? So, like, previous trials that have looked at all comers had patients with and without the genetic variant. And then other strategies that I'm more optimistic about are enriching for patients that have the genetic variant or go one step further identifying patients that maybe don't have the genetic variant but have a similar genetic profile to those that do have the genetic variant. So for example, is using SNPs or small regions within the genome to identify patients that look like those LRRK2 patients, even if they're not necessarily genetically having that variant. in doing so, they can identify a broader population, so about thirty percent of the population with Parkinson's rather than the small percentage less than, you know, five percent that have the true genetic variant. And so I think now being able to um enrich for patients that maybe, you know, don't necessarily have the genetic variant but could still be treated well by this type of therapy is a more powerful move. And so that's why I'm more optimistic about the target now

Simone Fishburn: 6:20

You know, one more quick question on this. So you know, with this particular mutation, first of all, do you see early onset Parkinson's or is it something that accumulates, you know, the damage accumulates over time, which is, is there sort of an age component to this? And then the SNPs, you know, you talk about the profile even in patients who don't have LRRK mutations. So maybe You could talk a little bit about how that pathology looks and if that's being used to segregate patients or um stratify, it's a better word, the patients

Lindsay Martin: 6:54

Yeah. So, okay, so your first question, can this be used in early-onset Parkinson's?

Simone Fishburn: 7:00

No, that's not actually… I'm sort of saying why, you know, you have the mutation from birth, right? It's a congenital mutation rather than one that's acquired, I assume. Right? And so is it that the accumulation of toxins sort of, you know, happens over decades and it sort of in your later years, or are there other factors that sort of trigger this as, as people get older?

Lindsay Martin: 7:24

I see. Okay. Yeah, so in patients that do have the genetic variant, the genetic variant and then overactivity of the kinase itself is what starts to trigger Parkinson's disease. So these patients have like genetic variant-driven Parkinson's. In patients that are, say, idiopathic, so not necessarily they have a specific genetic variant it could be a variety of factors that eventually lead to them having Parkinson's. And the thought is that patients that don't have the specific genetic variant but have SNPs that give them a similar genetic profile are still experiencing Parkinson's in a similar way to those that do have the genetic variant. So the cause is still the, overactivity of the kinase and the misfolding of the protein in the same manner, but they don't have that one-- like specific seven genetic variants that are traditionally thought to be the cause

Stephen Hansen: 8:19

Lindsay, I, I took a little sneak peek into your deck there, and obviously there was, there was quite a broad array of stuff you're digging into there. M-maybe give us a little bit of an overview as to what are the other sort of areas in, in the disease and, and, and sort of new findings that you've come across that you can maybe highlight. You know, maybe just pull out some of the highlights from there

Lindsay Martin: 8:36

Yeah. So we've talked a bit about the genetic targets um specifically LRRK2. There's other genetic targets that are being pursued in the clinic right now, like GABA or GCase and then alpha-synuclein, which is the top target in the clinic. And alpha-synuclein obviously is, the accumulation drives Parkinson's disease and Lewy bodies um having these toxic misfolded proteins. So the biological basis for targeting alpha-synuclein is strong. and so I think that we'll see a big advancement in targeting alpha-synuclein as well. We have a couple of targets that are more advanced in the clinic, two that are in Phase III right now, one in an open label extension, buntanetap from Annovis, and then prasinezumab from Prothena and Roche. and so those are gonna be some exciting readouts in the next few years. But really, I'm most excited, I think, about the cell therapies that are in the clinic right now. And so in March, Japan granted conditional authorization to the allogeneic cell therapy, Amchepry(raguneprocel) from Sumitomo. And this is the first cell therapy that has been approved for Parkinson's disease, the program is currently in Phase I and II testing in the US. There's a similar regenerative cell therapy from BlueRock, bemdaneprocel, that's also in Phase III testing in the US right now. And so I think we're going to see regenerative cell therapies as an emerging option to modify the root cause of Parkinson's disease. So the idea is that you're replacing the lost dopaminergic neurons rather than just treating the symptoms or addressing a specific protein or kinase

Simone Fishburn: 10:30

Well, we probably don't have time to get into that, but we'll follow that in the future because again, that has been on the list of, the to-do list for Parkinson's for a very long time 'cause it, the idea was you could just implant the neurons 'cause it's very really known which ones undergo degeneration. So it'd be interesting to see what's different now and why, why that might be shaping up

Lindsay Martin: 10:50

Yeah, I'll just add a quick bit on that. I think, like these really stand out from previous fetal cell therapies in that these are more homogenous cells that are being input into the patient's brain. And so they can know exactly what stage of proliferation or differentiation the cells are at. And so there's a, a safety advantage in using this newer next gen therapy as opposed to the previous fetal cell grafts. And I think that also lends to efficacy as well in having the, the graft survive and be a durable treatment for the patient

Stephen Hansen: 11:24

Great. Well, thanks Lindsay. Yeah, really looking forward to uh reading this through. I believe it's gonna be coming out sometime this week so everyone can check out that deck when it's available

Lindsay Martin: 11:34

Thanks, Stephen

Simone Fishburn: 11:36

Stephen um let's actually turn to another thing. I'm taking over your role for a nanosecond here um because I want to ask you a question now. So AZ has, you know, transformed itself in the last, I would say, decade as a major force in cancer. in parallel with that, obviously the biggest story at least from a science point of view or a, a drug development point of view, is obesity in the last few years. Now those two forces are combining. So what's, what's going on with AZ and building, building a footprint in obesity? Talk us through that

Stephen Hansen: 12:10

Yeah, happy to. So as you say, AZ's been sort of on this huge growth trajectory from, from a lot of other programs. But while a lot of that has come from deals outside of, of this area, they are, you know, they've been using sort of a combination of internal development and deal-making to bring together, you know, what's not by no means the deepest obesity pipeline in the industry. It, it-- They basically are getting a footprint in kind of each of the major sort of trending areas there. One thing people might not remember is that AZ is actually no stranger to GLP-1s, as they actually had the world's first once-weekly GLP-1 agonist uh Bydureon, if you remember that from years ago. That used to be originally an Amylin program. but it was only in type two diabetes. It really didn't have the efficacy to, to kind of be pursued in, in obesity. They still have that sort of history there. And basically they've kind of picked up that mantle again and kind of are, are now carrying it forward with, you know, a clinical pipeline that you know, is led by elecoglipron, which is their small molecule GLP-1 agonist that had phase 2B data presented at ADA uh this past month. That's one they licensed in from Eccogene, a Chinese company uh several years ago. So that's now moving into Phase III uh later this year. And behind that they have four other clinical programs. So these span from AZD6234 their amylin receptor program AZD9550, which is a GLP-1 glucagon dual agonist. AZ also spent, I think, around $1.2 billion earlier this year to get rights to a GLP-1 GIP receptor dual agonist. But the one that I'm really kind of, I think, most excited to see data for is a activin inhibitor program that they acquired via their takeout of SixPeaks couple years ago. So this is a subcutaneous antibody targeting the activin pathway. And just from a sort of quality weight loss perspective, this is one of those targets that potentially ideally is suited for not only delivering weight loss, but this high-quality weight loss because you have both hitting ALK7, which is reducing lipolysis and taking down sort of fat selective weight loss. But then at the same time, you're activating the myostatin pathway, so you're building muscle in the same way. So you know in talking to AZ, I think this was one of the programs that they were most excited about, and they were kind of outlining how they think they could potentially hit 10% weight loss as monotherapy with this, where if you think about 10% weight loss as a standalone monotherapy, that's pretty much in line with what we're seeing with most of the small molecule GLP-1s. It's in line with some of the amylin programs as well. And so while the activin's pathway had really kind of been thought about as really something that would be added on top of a GLP-1 to try and make the quality of the weight loss better, just wondering whether there's the potential for this just as a monotherapy as well. I mean

Simone Fishburn: 15:19

Stephen, is it a, is it a different patient population or a s- I mean, is it still obese patients or is it a, a subset? As you say, the population is so huge. Certainly if you get 1%, let alone 10%, you know, you can do some significant business there

Stephen Hansen: 15:35

Yeah, yeah. It's a great point, and, and I think that's what-- if you look at AZ's sort of decision-making around how they've selected their pipeline, I think it really reflects that, you know, what I think is that coming segmentation of the obesity market. So you have the oral therapy for patients that just want an oral, that don't want to do the injectable. You have sort of the, you know, they're gonna be testing their, dual agonists in combination with their amylin program, which could potentially drive, you know, much higher weight loss, so that's for the, the highly obese patient segment population. And then you have something like the activin, you know, pathway program uh AZD-1043, where that's probably really targeted at a more elderly frail population that might be more might have more risk of, of sarcopenia or these sorts of things. And, and each of these are, are on their own still huge markets. But you know, I think what we're seeing now is, you know, as these different targets can be segmented out towards different subpopulations of the-- of obesity patients, and I think AZ's really sort of trying to identify what those are and then, and then develop therapies that can go after each of them. So lots of data that should be coming in the next sort of year or so from this pipeline. And uh you know, I think they're very much gonna be trying to compete. As I said, they, they don't have the same depth that a Lilly or Novo does, but you know, they obviously have the commercial where-wherewithal to compete with them. And from the sounds of it, you know, they're, they're spending on manufacturing as well. So I think they're hoping that they'll be able to scale up and compete commercially there too

Simone Fishburn: 17:04

Yeah, I mean, it's looks like it's still gonna be an area that has a lot to give us in the next few years, certainly in terms of coverage

Stephen Hansen: 17:12

I think that's right. I think that's right. Yeah. keep everyone posted, but that story should be coming out later this week as well. So you can check it out at biocentury.com. Let's go to a break, and we'll be right back

Voice Talent: 17:23

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Stephen Hansen: 18:34

Welcome back to BioCentury This Week I think we need to uh maybe go to Washington and Steve. maybe we can start by talking about your three-part analysis of FDA's Operation TrialBlazer, which is the agency's attempt to reform and accelerate the conduct of clinical trials in the US So Steve, can you fill us in on uh what is Operation TrialBlazer and how it compares to getting a trial up and running in China?

Steve Usdin: 19:01

Yeah. So first, Operation TrialBlazer is not just FDA, it's an all of HHS plan. Um, but the most salient and certainly the most well-articulated parts of it are at FDA. basically it's a package of incremental reforms that taken together will slash the time required to launch a clinical trial in the United States if everything is executed according to plan. The timeline in the best case scenario in the United States to launch a, a Phase I trial would decrease to about fifteen months. Good news is that's less than half of what it takes now. the bad news, if you're benchmarking against China, is it's still about seven months longer than it takes in China. And then the question is what happens once you've got the trial started because another advantage that China has over the United States is the ability to very rapidly enroll once a trial is started. There are elements of Operation TrialBlazer that are intended to address that issue, but they're really not as robust or, or worked out as the other issues. The thing that I, I talk about in my story, if you're benchmarking against China, and it's relevant to benchmark against China because the Operation TrialBlazer report, it's about twenty pages long, and in that twenty pages it mentions China a dozen times, you know. So it, frames this initiative as a response to China. What they don't do in the report is actually compare what the United States does with China. They don't compare what the timelines are in the United States versus China. so I did it for them, and that's what, my story is all about, one of my stories. The most important thing, I think, if you're comparing the United States and China and TrialBlazer to what the reality in China is now, is that they take a different approach. What they're doing in China basically is they're doing a lot of the things that are being done in the United States sequentially, they're doing them in parallel. You know, it's really-- there's, there's a limit to how much you can compress the time to do certain things. The US approach is only gonna get you so far, right? And they've kind of maxed out again, if they implement what they've talked about, they've kind of maxed out on, on that part of it, at least until we have new technologies that dramatically reduce the need for um animal studies and things like that. But what the United States isn't doing is taking a more parallel approach like is being done in China, and honestly, it's also being done in other countries, in Australia and the UK to some extent. They're also looking at these parallel approaches. There's pluses and minuses to doing that. The main kind of negative in doing the kind of parallel approach that is being done in China is that it's higher risk, right? Because if you're doing a lot of, for example, the, preclinical uh toxicology, and you're doing other things in parallel with the ethics review and with the regulatory review, it's possible that you'll hit a snag or even a roadblock on one aspect of it, and you'll have done a bunch of other work you know, that won't be used. it'll, it'll be thrown out. And I've heard it described, the Chinese approach as kind of a, a brute force approach, right? And the United States is taking, takes a more you could say more elegant or more phased approach to the whole thing. But anyway, I think that, that's a summary of the US versus China aspect of it. If you want, we can spend a little bit of time talking about the

Simone Fishburn: 22:19

So Steve, yeah, I

Steve Usdin: 22:20

what they're doing.

Simone Fishburn: 22:21

I wanted to dig in because you started this with saying that, you know, the US is slashing timelines, right? And then you qualified that by saying it's half, but still longer than China. So one of the things that I find is that a lot of the conversation really is about China and about Australia, but there are plenty of other places in the world that we've been writing about that are also changing at the same time you know, trying to attract people to do clinical trials. And I sort of… I'm, I'm wondering, you know, this is gonna be a big focus for us going forward, but to what degree do you think this is all in sort of FDA policy hands versus the hands of other players like academic medical centers and, and pharma companies' decision-making and so on?

Steve Usdin: 23:07

Well, so, that's actually a good segue because the most interesting part of FDA's plan is to establish a network of what they're calling qualified research institutions, QRIs that include academic medical centers, CROs, regulatory advisors, and these are third parties that are gonna partner with sponsors to review IND components before their formal submission. That it's kind of an echo of or it's, it's reminiscent of what's done in Australia, but it's fundamentally different in o- in one important way, which is that in Australia, you have third party ethics committees that for low risk INDs have the authority to give the approvals or the okays for them to go ahead. In the United States, FDA is still gonna maintain that final say so on whether an IND can go ahead. But you're gonna see third parties playing a bigger role in the IND review process in the United States than they have in the past. But the big issues are things like contracting with hospitals, ethics reviews, trying to get single IRBs for multi-site clinical trials. And those are, those are in the plan, but they're things where the United States government has less leverage over it than some other countries do. It's a less centralized system. It's a more decentralized system in the United States than in other places. And, and one of the other things that I think that's structurally that's the most interesting is in China and in some other countries, hospitals themselves play a bigger role in the regulatory system than they do in the United States, and they have more authority, and they have more accountability for regulating clinical trials and in some cases you know, even early commercial access than in the United States. So it's, so it's a different model. I think it's really fascinating. We're seeing these different experiments, these different approaches tried around the world. What really needs to happen um ultimately, what's gonna be the best for patients and what's gonna be best for the biopharma industry is to kind of step back and say, you know, w-what are these different countries doing around the world that are the most effective, that's the most efficient, and then everybody around the world kind of trying to recalibrate all the um regulatory agencies and, and governments around the world trying to recalibrate to incorporate the best aspects of learnings from arou-ar-around the world. And this… Yeah.

Lindsay Martin: 25:28

Oh, I was just gonna touch on you, you mentioned uh hospitals having, I guess, obligation for trials and more of a responsibility. And I think one of the things that stood out to me in, in reading your TrialBlazer story was the planned components for trial access and enrollment, and how FDA can encourage clinicians to increase enrollment in the US. Can you speak a little bit more about, like, the details behind that?

Steve Usdin: 25:54

Well, it-- and I can't really give the details about it because the details aren't in the plan. That's part of the problem. That's kind of vague, and there's a little bit of, of-- I'd say a little bit of hand-waving in the, TrialBlazer report about that. But that really is one of the key things that has to happen in the United States. There has to be a more efficient system and a much broader scope for bringing patients into clinical trials. The percentage of patients who have cancers that can't be effectively cured in the United States who participate in clinical research is very small. it should be very, very large. Most, most cancer patients, I think, who who have a cancer that can't be readily controlled using an approved therapy should be on a clinical trial, and that's for their benefit, and it's also for the benefit of the system because it's gonna lead to faster innovation

Lindsay Martin: 26:44

Yeah, that was definitely something that came up at the Seattle Grand Rounds Conference too in discussing what are some of the actionable steps that, that we can do to increase trial enrollment. And, and yeah, I think having better patient education and clinician engagement will help with that

Steve Usdin: 27:00

Yeah. So one of the things that's in the plan, the, the TrialBlazer plan, is an idea to link electronic health records to clinicaltrials.gov so you can identify patients who would be good candidates for clinical trials. That's something that's gonna take long time to do. If it's done right and if it's done relatively fast, which will probably mean, you know, in, in the scope of a year or two or three to get going, that's something that potentially could increase clinical trial enr- enrollment in the United States if it's done along with other things in the package

Stephen Hansen: 27:33

So Steve, I wanted to uh to ask you about another one of your, your, the topics. Um, so you know, while FDA is moving forward on clinical trial reforms the agency's also taking a new look at therapies that were derailed under Martry Makary and Vinny Prasad's uh regime. I think we've counted up to 11 reversals so far in kind of what appears to be a, you might call a reversion to the mean. So can you maybe fill us in

Steve Usdin: 27:57

to the mean.

Stephen Hansen: 27:58

what you did call a reversion to the mean. So y- can you fill us in maybe on what the latest one of those was? And, you know, what I'm curious about is whether this signals to investors and companies a return to business as usual at FDA or, or not.

Steve Usdin: 28:12

so yeah, so, so I had a story last week. I, I totted up 11 products. They're not all products that have received approvals, but they're all products that either had a, a complete response letter or some other kind of setback that the company announced from advice from, from the path that they were on prior to uh Makary, Prasad, and now they seem to be back onto a more normal path. It's unlikely that every single one of them is gonna get approved, but probably a lot of them are going to be. The most recent one was Regenxbio's therapy for an MPS, for MPS II. That's a, a very rare neurodegenerative disease. FDA had i- issued a, a CRL and they basically had, They'd questioned or they'd, they'd said that they'd changed their mind about the kind of fundamental aspects, the endpoint, the clinical trial design, the patient population. And it really disheartened MPS II families. I spoke with some of the, the, the parents, and they were um they were devastated by this. They felt that FDA was completely off base in its assertions, and that they're really not only yanking the rug out from underneath kids who have MPS II who might benefit from this therapy, but more broadly from uh neurodegenerative diseases because investors would shy away from investing in any companies in the space as a result of what FDA had done. So now FDA has reversed its position according to a statement from the company. they're allowing the submission to proceed along the, the lines that it had been prior to Ma- Makary and Prasad. So you know, we'll, we'll see what happens, but this is something that the parents and other companies are watching really closely because it'll say a lot about whether, for example FDA is willing to accept external natural history controls in these very rare diseases. it's gonna say whether it's gonna go back on track, to honor the commitments that it had made earlier in the development program. And um you know, it seems like all that's gonna, gonna happen. You know, as we talked uh about, there's, 10 other programs that are also uh, getting back on track

Stephen Hansen: 30:24

Right. So, I mean, all this is happening under a sort of an interim leadership, correct, at FDA. And so I guess it raises, you know, the question it raises to me is, does this-- is there any risk that once new FDA leadership does step in, the permanent new leadership steps in, is there, is there any concern that, these, this kind of, this reversion to the mean could, could revert back to an outlier stance? You know, is this, is this the end of the political influence over FDA decision-making, or is it, is, is there still a risk that that could, that could rear its ugly head again?

Steve Usdin: 30:58

Look, this, this has been a rollercoaster ride under um in the second uh Trump administration, and uh anybody who predicts uh with, with real confidence where things are going is either extraordinarily uh knowledgeable or extraordinarily foolish. Uh, and I … So I'm not gonna, I'm not gonna try to do that. But I, I agree, yeah, look, it's really important who the next commissioner is. It's also gonna be important who's gonna take on the CDER and CBER directorship roles in a, a permanent basis. The rumors that are going around Washington are that uh we're gonna see a nomination for an FDA commissioner pretty soon. there are, you know, some names that are uh that are being talked about.

Stephen Hansen: 31:36

I was gonna say, do you have any, do you have any names?

Steve Usdin: 31:38

So, well, look, I've been holding off on, on naming the names. I've been hearing the same names that other reporters have been hearing for about a month. they, they're getting, they're getting named uh you know, more frequently now, so, so I'll bring them up. Look, so one of them is Heidi Overton. another one is uh Jeffrey Vacirca, and another one is Stephen Ferrara. Those are the three that seem to be in the lead. Overton is uh deputy director of the White House Domestic Policy Council. Before that, she was uh at the America First Policy Institute. She's closely aligned with the uh MAHA movement and, and with Makary. Vacirca is CEO of the Board of New York Cancer and Blood Specialists, and is past president of the Community Oncology Alliance. And Ferrara he's been chief medical officer for the Navy. He served in the CIA, and he's in a job at the, at the Pentagon now. None of the three of them are traditional candidates for the job. They're not, they don't

Stephen Hansen: 32:32

I'm gonna say it didn't, didn't sound like they have the same resumes of maybe past commissioners,

Steve Usdin: 32:37

No, no, they, they don't. So it's not really clear what they would do. I think that a- any one of them, if they get um confirmed, is likely to be under more control from downtown, from HHS, particularly from Chris Klomp who's effectively running HHS now, than Makary was. I think that the Trump 2 administration has kind of learned its lesson. It doesn't really want to see bold um you know, media, especially um high-profile media moves from um the FDA commissioner going forward. But we don't know what any one of these three really would do, what their attitudes would be. And a- again, I think that the critical thing, since none of them have deep experience at FDA, none of them have deep experience with the regulatory system, if any one of the three of these is nominated and confirmed, the, the really critical thing is going to be who's running CBER and CDER. And, and I think we're gonna find out all at once because the slate is gonna be announced all at once, and it, it could be as soon as this week

Stephen Hansen: 33:36

Yeah. Interesting. Well, I'm sure you'll be keeping abreast of the rumor mill, Steve, as uh as the week progresses, so you can look out for that. Otherwise you know, really fascinating. Thanks, Steve. Uh, you can find all of those stories on FDA reforms and renewed regulatory decisions at biocentury.com. I think that is all that we have time for today. Before you go don't miss our latest BioCentury Show in which my colleague Jeff Cranmer is in conversation with Hengrui's Frank Jiang, they go behind the curtain on deals and R&D at China's top biopharma company. Thanks for tuning in. we will see you next week