BioCentury This Week

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

• BioCentury • Season 6 • Episode 332

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With ObesityWeek yielding eye-catching amylin data and a bidding war that ran to $10 billion for Metsera, weight loss companies were center stage in biotech last week. On the latest edition of the BioCentury This Week podcast, BioCentury’s analysts explained why Pfizer's victory for the start-up over European rival Novo Nordisk doesn’t necessarily mean a broader U.S. policy shift against foreign acquisitions of domestic biotechs.
Turning to ObesityWeek readouts, they discuss Eli Lilly's data for amylin monotherapy eloralintide, arguing that just as Lilly did with GLP-1 agonists, the company is again setting the benchmark by which all other molecules in the class will be measured.
BioCentury's analysts also discuss takeaways from Washington Editor Steve Usdin's Commentary, which finds FDA in a crisis of politicized decisions, plummeting morale, and a hollowed workforce, and highlights from BioCentury's interview with gene therapy pioneer Jim Wilson as he rethinks the funding model for ultrarare disease therapies to keep his mission on track. This episode of the BioCentury This Week podcast is brought to you by Voyager Therapeutics.

View full story: https://www.biocentury.com/article/657545

#ObesityWeek #Amylin #GLP1 #Eloralintide #DrugMechanism #FDA #RareDisease #GeneTherapy

00:01 - Sponsor Message: Voyager Therapeutics 
01:53 - Pfizer Wins Metsera
08:48 - Lilly's Amylin Data
13:06 - Funding Ultrarare Therapies
20:51 - What's Next for FDA

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

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[AI-generated transcript.]

Eric Pierce:

BioCentury This Week is brought to you by Voyager Therapeutics. Voyager Therapeutics is dedicated to leveraging the power of human genetics to modify the course of – and ultimately cure– neurological diseases. Voyager addresses the challenge of delivering novel treatments to the brain through the company's innovative TRACER™ AAV capsid discovery platform, as well as Voyager's NeuroShuttle™, a non-viral delivery platform designed to transport multiple modalities of neurotherapeutics across the blood-brain barrier. The company's programs address diseases with substantial unmet needs, including Alzheimer's disease, Friedrich's ataxia, Parkinson's disease, ALS, and other diseases of the central nervous system.

Jeff Cranmer:

Pfizer has won the bidding war for Metsera. What can we learn from the week long wrangling between Pfizer and Novo for Metsera and what it means for cross-border M&A. Staying with obesity, a pair of amylin data sets made for an interesting ObesityWeek in Atlanta. Plus Jim Wilson, is rethinking the funding model for ultra rare therapies. P lus more leadership turmoil at FDA as Richard Pazdur declines the CDER job. But what's FDA going to look like moving forward? I'm Jeff Cranmer, and this is the BioCentury This Week podcast. Joining me are my colleagues.

Simone Fishburn:

Simon Fishburn, editor in chief.

Stephen Hansen:

Stephen Hansen, director of Biopharma Intelligence.

Lauren Martz:

Lauren Martz, executive Director of Biopharm Intelligence.

Steve Usdin:

And Steve Oden, Washington editor.

Jeff Cranmer:

All right, guys. Thanks for joining me. You all have quite different things to talk about, Stephen. I guess maybe you're glad that this, uh, week long, uh, bidding war is over. What, uh, where did the ball last bounce?

Stephen Hansen:

I think so it's been, uh, quite a wild week. 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. Then, on October 30th, Novo came in with a bid, arrival bid to acquire Metsera and sort of the bidding war started from there. in the intervening period we had Pfizer suing Novo and suing Metsera for breach of contract. there was, talk about, America first and these sorts of things. There's all this sort of drama that was happening in between, but kind of where it all landed was over the weekend. 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. So overall 10 billion, that basically equaled what Novo's final bid had been. then Novo announced over the weekend that it was, uh, basically pulling out that it was no longer gonna offer any, any new bids. 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. So, quite the sweetened deal from, where things stood.

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

Simone Fishburn:

So let me answer

Steve Usdin:

was that.

Simone Fishburn:

The answer's a ton. Okay, so Stephen and I have been talking about this. I think it is not possible to look at this course of events. 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. I believe this was done while the government shut down was still on. There's clearly a, a lot of FTC hand in this all I can say is, Lina Khan could have done this herself.

Steve Usdin:

So the, the, the question I guess that has going forward is, is, this one off? It seems, seems like these things are, are never one off. 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. going forward for the remainder of this administration.

Simone Fishburn:

think I, sorry, Steven, I know you wanna come into this, but I wanna add to that. I mean, there's that generally. But that's what you are calling the America first thing, Steve. But you know, you've got Bourla having cozied up to Trump. 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.

Stephen Hansen:

Yeah. So here's what I think I think there was a clear argument that this would've breached the antitrust. 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. And so why they went after this, you know, very unique structure that would put so much money up front. 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. 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. 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. And so I, I actually think Pfizer had a pretty good case to say that this wasn't gonna make it by. 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. I don't think Lilly could have gotten t his deal done with Metsera, with the same deal structure. 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. But I, I think just from an antitrust perspective, I think both Lilly

Simone Fishburn:

Stephen, what about the,

Stephen Hansen:

would've had a hard time

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? 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.

Stephen Hansen:

yeah, that's true. 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. But I think at this point in time. you know, few conversations I've had with some M&A lawyers as well. 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. Doesn't mean to say they can't do deals elsewhere. Like we've, we've seen the Lilly do and Novo obviously do due deal with obesity. Novo bought, you know, CB1, inhibitor. Which was, a different, molecule, different class. Lilly's done deals for bimagrumab you know, which is sort of the, activin antibody So there are deals to be done. I just think very narrowly in this GLP-1 class, this is one where it would be harder to forward from an antitrust position.

Simone Fishburn:

Okay. Last thing then. If they had this strong antitrust position, was sure of it and actually got that verified by Metsera in their announcement. Why did they have to up the bid? That's Pfizer. Why did Pfizer up the bid?

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. 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. I think if you try to go in with a lower offer, you make it much harder on Metsera to decide. And so I think, Pfizer's board was just finally like, you know what, whatever, just up the offer, make it an offer. They can, you know, this is like the, the Godfather offer, make'em an offer They can't refuse. And let's just move on with it.

Simone Fishburn:

Uh, all right. So I think that we can agree that basically they listened to our podcast last week and decided what's another billion between friends. And I also agree with you that from Metsera's point of view, it makes complete sense.

Stephen Hansen:

that's right.

Jeff Cranmer:

All righty. Thanks for that, Stephen. You were, uh, certainly on top of that. we didn't get you outta bed for anything, but, uh, you sort of waited to make your next story, make your next move. Okay. Well, Lilly sat on the sidelines of the Metsera madness, but it was making its mark in Hotlanta. For ObesityWeek, which wrapped up on Friday. SITC fans, we know you're out there, we'll get to you next week. but we're gonna stay with the obesity theme here. 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. Stephen, break this down for us.

Stephen Hansen:

Yeah, sure. Thanks Jeff. 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. and yeah, I mean, I guess the most impressive data out of the conference from my perspective, was the eloralintide, data from Lilly. It is an amylin receptor biased, agonist. and it was pretty impressive. So this was 48 week data. 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. and now the 48 week data showed nearly 20% placebo adjusted weight loss. I mean, that's pretty much on par with Lilly's Tirzepatide, so. Very impressive data. 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. 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. So it was a very promising sort of profile for, um, that program. 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. that was primarily because. 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. So I was always quite skeptical of the idea that you could get kind of GLP-1 like weight loss from an amylin monotherapy. 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. 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. There was a bit more weight loss from fat for Semaglutide than there was from the amylin arm of that study. And then on top of that, for the eloralintide data, they also had a body composition, subset of the data. 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. So. 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. 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. I mean, the rest of the data still looks great. It still is, GLP-1 like weight loss with better side effect profile. I think there's still a real role for amylin to play as a core obesity treatment. But, as of right now, I think we have to cut out the, uh, the muscle sparing mechanism.

Jeff Cranmer:

Well, thanks for the update, Stephen. What's next for you? What are you watching for?

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? I'm sure there's plenty of directions that, we can go from there. So,

Jeff Cranmer:

thanks for that, Stephen. I'm looking forward to that piece for sure. All right. Enjoy your evening, suspect it's dinner time for you right now. Well, let's turn to Lauren. 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. largely uninterested in the space. 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. Little more than a year in, uh, the hurdles he encountered, prompted him to, rethink the funding model to keep his mission alive. Lauren, what did you learn?

Lauren Martz:

Yeah, thanks Jeff. 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. So ultra rare diseases, were really at the center of the mission of Gemma, which launched a year ago when he left Penn. 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. There was a lack of interest from the VCs that, he approached in funding the ultra orphan, programs that he was trying to develop. 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. You know, this did require some VC funding, especially at the beginning. And, interest from VC simply wasn't there. 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. Um. 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. 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. And then the ultra rare programs were spun out into this new company, Rare Therapeutics.

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?

Lauren Martz:

So that was a core part of the original model. you know, there is this expectation that those programs when approved would get Priority Review Vouchers that was just built into the funding model. And so without that, I think that that is a big component to why this may not have worked. developing these ultra rare programs really does depend on the government, the FDA regulatory incentive. So there were the Priority Review Vouchers, which, you know, we still have vouchers. They're not as predictable. They're not gonna be or they may not be for these, these types of indications as we've seen

Steve Usdin:

they're, and they, they're, they call 'em vouchers. They're not vouchers because they can't be transferred, they can't be sold. 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. The key thing about that was that they were, um, you know, Willy Wonka's magic ticket. You, you could, transfer them or you could sell them, for, you know, north of a hundred million dollars usually. that's a powerful incentive for developing these kinds of drugs. 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.

Lauren Martz:

Exactly. I think this is a demonstration of that. And I think there are sort of other incentives that this was depending on. So there's also this platform technology designation, which we have been seeing rollouts. You know, there have been two companies at this point that have received this designation, but. Again, that's something that's unpredictable. 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. 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. 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. When I spoke with Jim Wilson, he also cited some potentially more reliable incentives. 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. 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.

Steve Usdin:

And we're also gonna be seeing the plausible mechanism pathway, at least that's what it's been called to date. Some kind of a, a new pathway that FDA is creating for ultra. Rare diseases that's gonna be announced, I think, uh, probably this week, but if not this week, then next week.

Jeff Cranmer:

Okay, thanks for that, Lauren. 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. And speaking of. The show notes while you're, uh, checking those out. Uh, don't forget to like and subscribe BioCentury This W eek and check out our sister podcast, The BioCentury Show. Steve, you, uh, are looking very dapper today. You've got a green screen behind you. What's, what's on your agenda?

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. 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.

Jeff Cranmer:

Alright. I'm looking forward to that. Yes, Simone did, uh, announce a new editorial policy where one of us has to wear a suit. every day. So, uh,

Simone Fishburn:

to see how this plays out, you know?

Jeff Cranmer:

yeah, me, me too. I mean, today, Eagles attire. Big, big Monday night game. But, uh, hey, we're gonna get back to Steve and what's happening in Washington, right after this.

Alanna Farro:

BioCentury This Week is brought to you by The 5th East-West Biopharma Summit in South Korea. An arc of innovation is emerging across Asia, and Western biopharma leaders are taking note-from cross-border deals to newcos. In March, 2026, The 5th BioCentury-BayHelix East-West BioPharma Summit visits South Korea for the first time. Meet the biopharma leaders putting Korea innovation on the global map. Learn why Korea has become a clinical trial in manufacturing hub. Discover if Korea is the next hotspot for NewCo formation. Plus, meet biopharma innovators from India to Singapore, to China and Japan. Register now at BioCenturyEastWest.com.

Jeff Cranmer:

And I have already begun recruiting, presenting companies for the East-West Summit. You can register now, to be a delegate. take advantage of that early bird rate. You'll wanna lock in your schedule once JP Morgan happens. we know how that is. it's, uh, hold onto your hats. 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. What is going on with leadership at FDA right now?

Steve Usdin:

Well, so here's what we know when we're talking about CDER. Um. We know, and you know, as I mentioned last week of George Tidmarsh is not coming back. Yeah, FDA Commissioner Makary asked Oncology Center of Excellence Director Richard HHS Secretary Robert F. Kennedy Jr., interviewed Pazdur. And I think it's important to point out that this is unprecedented. It's unprecedented for an HHS secretary to vet an FDA center director. But here's what I think, I think the job of the center director has become politicized. In the best of times, it's a really difficult job, and in the current administration it has become much more difficult. Whoever takes the position will have to be aligned with Kennedy's MAHA movement. 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. Previous CDER directors and CBER directors have had the confidence that since they're civil servants, that they will. stay in the position for, a lengthy period of time. 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. 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. And you can't really emphasize how important for the biopharm industry and for patients, the CDER director role is. in many ways it's more important than the FDA Commissioner

Simone Fishburn:

So Steve, Obviously there was Janet Woodcock for a very long time. Then Patrizia Cavazzoni Janet was there for so long, Dr. 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. 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? I'm really gonna do, you know, big things. think that's one of my concerns is the risk aversion that people at FDA will have, despite many things that. Makary is talking about in terms of making drug development easier, there seems to be a concern about sticking your head out.

Steve Usdin:

Yeah. 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. 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. There's gonna be more and more of those things. So whoever comes into the position is gonna have to be. Comfortable dealing with, that environment? What does that mean? Yeah. 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. we're going to see less predictability, and we're gonna see more erratic decision making. And by erratic decision making, I mean decisions that are made. Then there's political blowback and FDA changing its mind. There have been several instances of that already in this administration, and I think, we're going to see more. There's quite a bit of concern about some of the complete response letters that have been issued in recent weeks and months. 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. So I think that's the kind of thing that we're gonna see. 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. 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. in many cases, people who have been there for a decade or more who are going to do their utmost to keep the ship. You know, going to keep the ship afloat and, and, and going in the right direction. 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. The problem, I think, among other problems is that it's unpredictable when things will, blow off course. You know, everything. It's gonna be going along just as you expect. And then for some reason, things aren't going along the way that you expect anymore. that's gotta be in the back of, everybody's mind.

Jeff Cranmer:

Alright, thanks for that update, Steve. yeah, definitely, uh, much gratitude to those people. keeping the light on moving, applications, giving companies advice. we need it. for those of you doing that, hang in there. Okay. Well, don't forget to turn into The BioCentury Show this week. we'll also have another special pod for you, Simone and Josh. we're up in Boston at the Venture Café Cambridge last week, a really good podcast focused on, all things Korea. one can only hope that Josh has finally seen, K-pop demon hunters. I know Simone, uh, lives it basically. So. on my to-do list. It is on my to-do list. I have to tell you, my husband cannot believe it is on my to-do list, but it is. Just as soon as I finish Shogun, I gotta finish Shogun, first. Oh, yeah. Yeah. I

Simone Fishburn:

Yeah. Yeah.

Jeff Cranmer:

Yeah. All right. All right. Well, you got some plane rides ahead of you, so hopefully you can make some, uh, some headway on both fronts. Okay. thanks for tuning in. We will catch you for our regular pod, next week. Kendall Square Orchestra provides the music for BioCentury's Podcasts. Tickets are now on sale for the Group's eighth season. 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.

Eric Pierce:

BioCentury would like to thank Voyager Therapeutics for supporting the BioCentury This Week podcast. To learn more about Voyager's programs advancing transformative medicines for neurological diseases, visit voyagertherapeutics.com.

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