Ep. 353 - Prasad Departure and Future of Fibrosis Therapies

WEBVTT

00:00:00.000 --> 00:00:02.134
[AI-generated transcript.]

00:00:02.134 --> 00:00:04.371
<v Stephen Hansen>It is deja vu all over again.

00:00:04.471 --> 00:00:12.412
<v Stephen Hansen>As for the second time in the past eight months, Vinay Prasad is out at FDA, what happened and what it means for the agency going forward.

00:00:12.846 --> 00:00:19.219
<v Stephen Hansen>Plus how the science has reached a tipping point in halting fibrosis, one of industry's most persistent challenges.

00:00:19.818 --> 00:00:23.757
<v Stephen Hansen>And the latest clinical updates on psychedelics and obesity therapies.

00:00:24.024 --> 00:00:29.728
<v Stephen Hansen>I'm Stephen Hansen, Co-host of the BioCentury This Week podcast, and joining me today are my colleagues.

00:00:30.730 --> 00:00:33.566
<v Lauren Martz>Lauren Martz, executive Director of Biopharma Intelligence.

00:00:34.234 --> 00:00:35.935
<v Selina Koch>Selina Koch, Executive Editor.

00:00:36.235 --> 00:00:37.804
<v Steve Usdin>And Steve Usdin, Washington Editor.

00:00:38.470 --> 00:00:48.048
<v Stephen Hansen>All right, well, before we dive into those topics, a few of our colleagues, Jeff, Simone, and a few others are over in Seoul for our 5th annual BioCentury BayHelix East-West Summit.

00:00:48.381 --> 00:00:49.381
<v Stephen Hansen>which is starting today.

00:00:49.649 --> 00:01:06.399
<v Stephen Hansen>And launching at the East-West Summit we are excited to introduce a new exclusive opportunity for BioCentury subscribers, step inside the BioCentury Lounge, a dedicated space designed to connect, recharge, and inspire conversation among industry leaders.

00:01:06.665 --> 00:01:12.971
<v Stephen Hansen>Experience unique networking moments, insider insights, and a place to unwind between sessions.

00:01:13.305 --> 00:01:13.906
<v Stephen Hansen>Don't wait.

00:01:13.972 --> 00:01:16.341
<v Stephen Hansen>Check out more at BioCenturylounge.com.

00:01:17.644 --> 00:01:19.813
<v Steve Usdin>Can, can we get one of those lounges in Washington?

00:01:21.246 --> 00:01:22.816
<v Stephen Hansen>I'm sure we can work something out for you, Steve.

00:01:22.816 --> 00:01:25.751
<v Stephen Hansen>I'm sure we can get you, uh, get you a little space to relax there.

00:01:25.819 --> 00:01:26.585
<v Stephen Hansen>You don't already have one?

00:01:27.087 --> 00:01:27.319
<v Steve Usdin>No.

00:01:27.319 --> 00:01:31.391
<v Steve Usdin>Well, I like the, you know, the unique, uh, networking and all that kinda stuff that, that sounded really fun.

00:01:33.692 --> 00:01:34.861
<v Stephen Hansen>Well, I'm sure we can figure something out.

00:01:34.861 --> 00:01:36.695
<v Stephen Hansen>I, you know, give, uh, give Josh a call.

00:01:36.695 --> 00:01:38.364
<v Stephen Hansen>I'm sure he can, uh, he can sort you out.

00:01:38.531 --> 00:01:49.409
<v Stephen Hansen>But in the meantime be before we get Steve, his, own personal BioCentury lounge, um, we're also looking ahead to this year's Bio€quity conference, which is happening in Prague at the beginning of May.

00:01:49.843 --> 00:01:55.948
<v Stephen Hansen>so if you have any companies that are interested in presenting this year, please do reach out, to Jeff, for more information on that.

00:01:56.316 --> 00:01:56.882
<v Stephen Hansen>Right.

00:01:56.950 --> 00:01:59.418
<v Stephen Hansen>So Steve, you're just getting back from what?

00:01:59.786 --> 00:02:08.161
<v Stephen Hansen>What I was hoping was, you know, a nice relaxing vacation from what you've told me before we started recording here, doesn't sound like it was as relaxing as you might've hoped it would've been.

00:02:08.527 --> 00:02:10.963
<v Stephen Hansen>Uh, you can de decide whether you wanna disclose that or not.

00:02:11.296 --> 00:02:21.407
<v Stephen Hansen>but you know, you come back to, um, Vinay Prasad out at FDA first off, is this gonna be our last conversation about Prasad at fda a or not?

00:02:21.407 --> 00:02:22.808
<v Steve Usdin>No, of course not.

00:02:22.908 --> 00:02:29.115
<v Steve Usdin>You know, he's been fired once we, you know, this is a second time, you know, is he gonna come back for a third round?

00:02:29.481 --> 00:02:30.182
<v Steve Usdin>I doubt it.

00:02:30.250 --> 00:02:33.887
<v Steve Usdin>but is he going to just, you know, uh, slink off into the sunset?

00:02:33.887 --> 00:02:34.086
<v Steve Usdin>No.

00:02:34.086 --> 00:02:41.728
<v Steve Usdin>I doubt that also he is going to, definitely be a character who's gonna be in the, in the ecosystem for some time, but.

00:02:41.995 --> 00:02:45.330
<v Steve Usdin>anticipating your question, you know, why, you know, and why now?

00:02:45.365 --> 00:02:46.832
<v Steve Usdin>Why, why, why was he fired now?

00:02:46.866 --> 00:02:48.800
<v Steve Usdin>I mean, uh, yeah, what happened?

00:02:48.800 --> 00:02:49.169
<v Steve Usdin>Okay.

00:02:49.568 --> 00:02:52.972
<v Steve Usdin>I, I think that it, it can be all summed up in a word, which is hubris.

00:02:53.372 --> 00:02:57.644
<v Steve Usdin>And, and it's the same thing that led to his ouster the first time.

00:02:58.110 --> 00:02:59.945
<v Steve Usdin>In a way, you know, in a big way.

00:02:59.945 --> 00:03:00.847
<v Steve Usdin>This was personal.

00:03:00.847 --> 00:03:05.185
<v Steve Usdin>It was about his personal behavior, but it, it's also institutional.

00:03:05.651 --> 00:03:08.921
<v Steve Usdin>And I think that the institutional part gets to what comes next.

00:03:08.921 --> 00:03:11.157
<v Steve Usdin>But first, you know the personal part.

00:03:11.524 --> 00:03:19.132
<v Steve Usdin>He treated patients, FDA staff, drug companies, the scientific community, and the public with complete contempt and arrogance.

00:03:19.431 --> 00:03:29.741
<v Steve Usdin>His lack of concern for the impact of his decisions on DMD patients led to his first firing, FDA staff who worked for and with him describe his behavior as off the charts.

00:03:30.109 --> 00:03:34.614
<v Steve Usdin>Threats, foul languages, allegations of harassment and, and more.

00:03:35.080 --> 00:03:38.850
<v Steve Usdin>His refusal to accept an application for Moderna's flu vaccine.

00:03:39.284 --> 00:03:48.594
<v Steve Usdin>Uh, and his treatment of uniQure, along with his disdain for advisory committees, reflect his contempt for scientific expertise and accompanies that turn science into medicine.

00:03:48.995 --> 00:03:58.003
<v Steve Usdin>The institutional part, it's a mistake to look at specific decisions Prasad made and try to evaluate were they good or they bad.

00:03:58.437 --> 00:04:01.907
<v Steve Usdin>You know, there's this old trope about a swinging pendulum at FDA.

00:04:02.442 --> 00:04:03.909
<v Steve Usdin>It really doesn't apply here.

00:04:04.276 --> 00:04:10.349
<v Steve Usdin>What really matters, I think, is not what decisions that he made, but how the decisions were made.

00:04:10.883 --> 00:04:18.124
<v Steve Usdin>For years, I cringed when people said, oh, the FDA commissioner or a center director approved or rejected a specific drug.

00:04:18.124 --> 00:04:22.427
<v Steve Usdin>And I tried to explain that their large teams of experienced reviewers who make decisions.

00:04:23.362 --> 00:04:29.035
<v Steve Usdin>And that the Commissioner never makes approval decisions and center directors very rarely become involved.

00:04:29.502 --> 00:04:32.137
<v Steve Usdin>Makary, and Prasad threw all of that out the window.

00:04:32.605 --> 00:04:39.711
<v Steve Usdin>So whether you agree or disagree with specific decisions, I think everyone loses when one or two individuals are making decisions.

00:04:39.745 --> 00:04:49.889
<v Steve Usdin>They're picking winners and losers, and the fact that those decisions are influenced by politics and by an unscientific ideology, and that's what Maha is, you know, makes it even worse.

00:04:50.656 --> 00:05:00.632
<v Steve Usdin>And I think this explains the disconnect between Prasad's and Makary's promises to promote rare disease therapies and their actions, but none of this was why Prasad was pushed out.

00:05:00.833 --> 00:05:02.735
<v Steve Usdin>I think it was a culmination of factors.

00:05:02.735 --> 00:05:13.713
<v Steve Usdin>One was his war on vaccines and on mRNA technology in particular, HHS Secretary Kennedy, Makary were totally on board with those views and they wanted him to pursue anti-vaccine policies.

00:05:14.146 --> 00:05:16.149
<v Steve Usdin>But those policies don't poll well.

00:05:16.214 --> 00:05:19.918
<v Steve Usdin>The White House has been seeing polls about vaccines and about mRNA.

00:05:20.218 --> 00:05:35.201
<v Steve Usdin>Winning the midterms is the top priority for the White House Pfizer, CEO Albert Bourla publicly attacking Prasad's vaccine policies, and my guess is that his and other CEO's private calls to the White House made Prasad a political liability.

00:05:35.600 --> 00:05:40.706
<v Steve Usdin>The string of reversals and setbacks for rare disease therapies also created political blowback.

00:05:41.139 --> 00:05:44.343
<v Steve Usdin>So I think all of those things kind of combined, to push him out.

00:05:44.911 --> 00:05:52.617
<v Stephen Hansen>So Steve, are you saying that this, this would've been a, the White House's call to make that this wouldn't have been someone at HHS or Makary, who would've made this call?

00:05:53.019 --> 00:05:54.153
<v Steve Usdin>Well, it certainly wasn't Makary.

00:05:54.286 --> 00:05:57.122
<v Steve Usdin>Makary and Prasad were joined at the hip.

00:05:57.656 --> 00:06:02.728
<v Steve Usdin>Makary never passed up an opportunity to call Prasad a genius.

00:06:02.762 --> 00:06:04.697
<v Steve Usdin>He used that word repeatedly over and over again.

00:06:04.697 --> 00:06:07.666
<v Steve Usdin>He lavish praise on him, even very recently he did that.

00:06:07.666 --> 00:06:11.903
<v Steve Usdin>So I think that there's, there's no way that this was Makary's call.

00:06:12.672 --> 00:06:21.581
<v Steve Usdin>It's possible that it was Kennedy's, but I think that, especially in an election season, a decision like this had to have come from the White House.

00:06:21.848 --> 00:06:23.516
<v Steve Usdin>I know that there was a lot of pressure.

00:06:23.516 --> 00:06:25.117
<v Steve Usdin>There were people who are calling the White House.

00:06:25.617 --> 00:06:41.466
<v Steve Usdin>CEOs and, uh, other people who were influential, calling for Prasad's ouster the Wall Street Journal's campaign against him was no secret, you know, neither was, uh, the editorials that, that I wrote calling for the industry to, um, demand his, his ouster.

00:06:42.000 --> 00:06:45.571
<v Selina Koch>And Albert Bourla did as well in public very recently, the same week.

00:06:45.704 --> 00:06:48.173
<v Selina Koch>I think a few days before he was kicked out.

00:06:48.473 --> 00:06:49.442
<v Steve Usdin>E. Exactly.

00:06:49.709 --> 00:06:57.583
<v Steve Usdin>So I think it's a mistake though to focus entirely on Prasad, and if you're trying, and the key thing now is to think about, well, what happens next?

00:06:57.583 --> 00:06:57.916
<v Steve Usdin>Right?

00:06:58.651 --> 00:07:03.122
<v Steve Usdin>the thing that I think is, was really disturbing about Prasad, besides his personal behavior.

00:07:03.656 --> 00:07:11.730
<v Steve Usdin>Is the view that one or two people can and should make decisions about approvals, about public health and about the fate of people with serious diseases.

00:07:12.064 --> 00:07:14.766
<v Steve Usdin>And that reflects Makary's views also.

00:07:15.000 --> 00:07:18.971
<v Steve Usdin>That's what the Commissioner's National Priority Voucher program is about.

00:07:19.838 --> 00:07:28.915
<v Steve Usdin>Makary's also completely on board with the idea that external scientific advice that the views of patients are obstacles rather than essential aspects of the regulation of medical products.

00:07:28.915 --> 00:07:29.548
<v Steve Usdin>He's made that clear.

00:07:30.415 --> 00:07:39.158
<v Steve Usdin>And he's engaged in one of the things that Prasad did, speaking about pending drug applications, which some lawyers and lawmakers say is illegal.

00:07:39.759 --> 00:07:47.432
<v Steve Usdin>And Makary's promoted the idea that Tylenol causes autism and Leucovorin can treat autism messages that aren't backed up by scientific evidence.

00:07:47.966 --> 00:07:59.778
<v Steve Usdin>And he's committed to the idea that it makes sense to cherry pick some applications based on factors that include pricing and adherence to President Trump's MFN policies, for preferential treatment.

00:08:00.278 --> 00:08:04.884
<v Steve Usdin>Here's another thing that Makary did when he was asked on CNBC about prasad's politics.

00:08:05.418 --> 00:08:11.057
<v Steve Usdin>He said that Prasad had supported Bernie Sanders in the past, but now he's a staunch supporter of Trump.

00:08:11.490 --> 00:08:24.569
<v Steve Usdin>I think that the only thing that's more inappropriate than a journalist asking an FDA Commissioner about the personal politics of an agency employee is a commissioner answering the question, you know, this is not something that should be done.

00:08:24.971 --> 00:08:26.771
<v Steve Usdin>Disease doesn't know any politics.

00:08:27.005 --> 00:08:32.211
<v Steve Usdin>Patients don't care about the politics of FDA employees and they, and they shouldn't.

00:08:33.078 --> 00:08:40.552
<v Steve Usdin>So we know, that HHS Secretary Kennedy's gonna be involved in picking or approving Prasad's successor and likely the White House.

00:08:40.852 --> 00:08:43.855
<v Steve Usdin>And that leads to real questions about, who it's gonna be, but also.

00:08:44.190 --> 00:08:46.424
<v Steve Usdin>What kind of person it is, what are the criteria gonna be?

00:08:46.424 --> 00:08:59.871
<v Steve Usdin>So, you know, here's what I'm looking for, you know, is the person gonna be selected based on experience, temperament, and qualifications, or is loyalty to Trump and Kennedy and the Maha ideology, the criteria we already saw.

00:08:59.871 --> 00:09:02.642
<v Steve Usdin>What happened when George Tidmarsh was forced out at CDER.

00:09:03.275 --> 00:09:09.649
<v Steve Usdin>You know, if you made a list of a thousand people who are qualified to lead CDER, Tracy Beth Høeg wouldn't be on it.

00:09:10.182 --> 00:09:19.692
<v Steve Usdin>She's there because she has sped views on COVID that are in sync with Kennedy and Makary, and both of them view her as loyal, but she's not qualified to run CDER.

00:09:20.091 --> 00:09:22.727
<v Steve Usdin>another question, is the appointment intended to be lasting?

00:09:23.062 --> 00:09:31.169
<v Steve Usdin>Because now Makary, he's spending Prasad's time at FDA as a sabbatical that he took a sabbatical from his academic position to come into government.

00:09:31.803 --> 00:09:35.841
<v Steve Usdin>You know, that's not the way that it was described when he came in, uh, initially.

00:09:36.274 --> 00:09:40.145
<v Steve Usdin>And it's not the way that center directors have traditionally been viewed.

00:09:40.546 --> 00:09:43.381
<v Steve Usdin>and it's not a way to create a stable environment.

00:09:43.515 --> 00:09:46.818
<v Steve Usdin>at the center, does the new CBER director come in with an agenda?

00:09:47.086 --> 00:09:49.822
<v Steve Usdin>And if he does, or she does, is it Maha?

00:09:50.121 --> 00:09:53.926
<v Steve Usdin>Does it include reviving morale at the center, which is incredibly low.

00:09:54.293 --> 00:09:59.030
<v Steve Usdin>Does it include trying to bring some of the people Prasad pushed out, back into FDA.

00:09:59.398 --> 00:10:06.739
<v Steve Usdin>And will they, will they create a climate for people who were pushed out or felt that they had to leave will be comfortable coming back?

00:10:06.739 --> 00:10:19.217
<v Steve Usdin>Remember that, one of the big factors in, Rick Pazdor's decision to resign as CDER director was Makary's tolerance for Prasad's actions and, demands

00:10:20.152 --> 00:10:32.865
<v Stephen Hansen>So Steve, I mean, you know what, I think in some ways what you're getting at, what it kind of comes down to is, you know, is this gonna fundamentally change anything in terms of the way that CBER operates or, or approaches things relative to how Prasad was, was operating it.

00:10:32.898 --> 00:10:53.686
<v Stephen Hansen>'cause I mean, just one, I mean one small data point here, but obviously, you know, you mentioned uniQure earlier, who was at the center of kind of the most recent, um, sort of drama, around FDA and their stock, you know, investors are reacting as if Prasad was maybe not the only, but one of the primary sort of barriers to their, to their Huntington's disease gene therapy.

00:10:54.253 --> 00:10:56.054
<v Stephen Hansen>Is that kind of the right way to think about it?

00:10:56.054 --> 00:11:04.330
<v Stephen Hansen>Or is the, or is the expectation that someone's gonna come in, who's gonna continue to espouse similar viewpoints?

00:11:04.797 --> 00:11:08.967
<v Selina Koch>I mean, do we just, I'm gonna add onto that question.

00:11:09.201 --> 00:11:10.535
<v Selina Koch>What about Makary's role here?

00:11:10.936 --> 00:11:12.804
<v Selina Koch>I mean, he does look at individual things, right?

00:11:13.438 --> 00:11:14.539
<v Selina Koch>Where does he fit into this?

00:11:14.907 --> 00:11:22.715
<v Steve Usdin>So, so, you know, it, it's, it's difficult to, to predict exactly, but I, I think some things are pretty sure that to happen.

00:11:22.914 --> 00:11:27.886
<v Steve Usdin>I think that whoever comes in, they're gonna have a mandate to not generate news.

00:11:27.886 --> 00:11:28.187
<v Steve Usdin>Right.

00:11:28.220 --> 00:11:40.399
<v Steve Usdin>I've written before that the last thing that any president really wants to see is the FDA Commissioner on the news or the FDA in general on the news,'cause it's never good news for the administration when that happens, or very rarely.

00:11:40.899 --> 00:11:49.240
<v Steve Usdin>I think that whoever comes in, at least between now and the midterms, is gonna be under instructions to keep a lid on, on vaccine controversies.

00:11:49.575 --> 00:11:54.613
<v Steve Usdin>To avoid, controversies involving, um, rare disease drug approvals.

00:11:55.014 --> 00:12:04.923
<v Steve Usdin>Whether that extends to the reversing some of the decisions, that Prasad made, that really upset, uh, important constituencies, is uncertain, right?

00:12:05.423 --> 00:12:08.326
<v Steve Usdin>I think that, certainly, it can't be bad news.

00:12:08.494 --> 00:12:10.763
<v Steve Usdin>For uniQure, for Huntington's disease patients.

00:12:11.163 --> 00:12:13.631
<v Steve Usdin>By the way, I think it's a mistake to focus on uniQure.

00:12:13.631 --> 00:12:29.981
<v Steve Usdin>I think that the, the people to focus on is the Huntington's disease community and the fact that they have had what seems like the first disease modifying therapy or potentially disease modifying therapy, if not snatched away from them certainly delayed.

00:12:30.850 --> 00:12:46.966
<v Steve Usdin>Then they've been, subjected to this, uh, notion from FDA that patients should undergo sham therapy and be willing to receive a placebo, and then wait for, outcomes for, a uniformly terrible disease that takes some time to progress.

00:12:47.265 --> 00:12:48.634
<v Steve Usdin>You know, that's really horrible.

00:12:49.201 --> 00:12:54.440
<v Steve Usdin>So, because they're making decisions that I, that are based on politics rather than public health decisions.

00:12:54.506 --> 00:12:59.311
<v Steve Usdin>I think the Prasad's replacement and Makary face some really tough choices.

00:12:59.879 --> 00:13:07.986
<v Steve Usdin>And, and as a result of that, my guess is that the next person in the job may not last very long, even if it is somebody who they have the intention to keep there for some time.

00:13:08.721 --> 00:13:18.062
<v Steve Usdin>Like I said, the, the administration wants to keep vaccines out of the news ahead of the midterm elections, but FDA is gonna have to make a decision about Moderna's flu vaccine this summer.

00:13:18.530 --> 00:13:21.000
<v Steve Usdin>Rejecting the vaccine would cause a furor.

00:13:21.667 --> 00:13:28.506
<v Steve Usdin>So would approving it, the Maha base is furious about the Trump administration's support for the Roundup herbicide.

00:13:28.774 --> 00:13:49.595
<v Steve Usdin>They'll be even more energized and upset by a vaccine approval, and it isn't really possible just to kick the can down the road either, because if an approval decision isn't made at some point during the summer, it'll become too late to get a vaccine manufactured and deployed in time for the upcoming flu season.

00:13:50.095 --> 00:13:56.501
<v Steve Usdin>So, um, that's gonna be a really tough decision that FDA's gonna have to make whatever decision they make, they're gonna upset somebody.

00:13:57.068 --> 00:14:04.475
<v Steve Usdin>Uh, I think that there are a number of other decisions that are gonna be coming up that are similar, where there are constituencies on both sides of it.

00:14:05.076 --> 00:14:36.908
<v Steve Usdin>And this is exactly the reason why in the past it's been, you know, really, uh, dogma, FDA, that you avoid even the appearance of political interference in decision making because decisions often upset somebody, some constituency, and if you're bowing to, uh, one constituency or another, and it's even so extreme that, um, it results in, firing of, of staff and, and things like that, you get really into, um, an untenable situation very quickly.

00:14:37.710 --> 00:14:42.881
<v Stephen Hansen>Any early leaders in the clubhouse, Steve, in terms of who might be taking over at CBER yet?

00:14:43.215 --> 00:14:49.687
<v Steve Usdin>You know, I'm hearing rumors, but they're rumors and I don't think it does anybody any good for me to, um, repeat them right now.

00:14:50.589 --> 00:14:50.990
<v Stephen Hansen>Fair enough.

00:14:50.990 --> 00:14:55.494
<v Stephen Hansen>Well, maybe that'll be a topic for another, another pod to come here as we get, uh, get a bit more information.

00:14:55.494 --> 00:14:55.894
<v Stephen Hansen>But thanks

00:14:55.961 --> 00:14:57.328
<v Steve Usdin>prob probably next week.

00:14:57.395 --> 00:15:02.201
<v Steve Usdin>And by the way, by the way, um, you you, you asked about, you know, is this the last we're gonna be hearing about Prasad.

00:15:02.433 --> 00:15:04.769
<v Steve Usdin>It, it's also important to note he is not gone, right?

00:15:04.769 --> 00:15:09.207
<v Steve Usdin>He's, he is, um, supposed to stay until, uh, you know, for another month or so.

00:15:09.475 --> 00:15:14.613
<v Steve Usdin>Uh, so, we may be hearing some other things, from him and from FDA in that time period.

00:15:15.447 --> 00:15:15.714
<v Stephen Hansen>Yeah.

00:15:16.682 --> 00:15:17.149
<v Stephen Hansen>Thanks, Steve.

00:15:17.149 --> 00:15:18.683
<v Stephen Hansen>That's super interesting insights there.

00:15:18.783 --> 00:15:26.457
<v Stephen Hansen>Um, as you said, probably is not gonna be the last bit of drama coming outta FDA that we're gonna hear about, but, um, appreciate it.

00:15:26.792 --> 00:15:29.327
<v Stephen Hansen>Um, I'd like to now move on to, uh, to Lauren.

00:15:29.394 --> 00:15:35.734
<v Stephen Hansen>so Lauren, you published last week, uh, the first of what I think is gonna be sort of a series of stories on fibrosis, right.

00:15:35.868 --> 00:15:43.008
<v Stephen Hansen>with IPF in particular, what did you find in terms of sort of industry progress towards new antifibrotic mechanisms?

00:15:43.875 --> 00:15:44.610
<v Lauren Martz>Thanks, Steve.

00:15:44.643 --> 00:15:56.054
<v Lauren Martz>Yeah, so I focused on IPF because this was an indication where we haven't seen until December, there has not been a new drug approval for about a decade.

00:15:56.488 --> 00:16:01.961
<v Lauren Martz>So in December, Boehringer got an approval for nerandomilast.

00:16:02.293 --> 00:16:08.533
<v Lauren Martz>and this is adds to two drugs that were approved, uh, over 10 years ago for this indication.

00:16:08.801 --> 00:16:16.774
<v Lauren Martz>But all three of these therapies are known to effectively slow progression of this idiopathic pulmonary fibrosis IPF.

00:16:17.442 --> 00:16:28.553
<v Lauren Martz>There's still a ton of opportunity to stop progression or potentially even reverse fibrosis in this indication and in many, many other diseases with fibrotic pathology.

00:16:28.953 --> 00:16:37.096
<v Lauren Martz>I thought this was just an interesting place to see, what other progress is happening because when we look to liver fibrosis and, and all of the progress in mash.

00:16:37.596 --> 00:16:42.167
<v Lauren Martz>There is evidence now that you can actually reverse some of the fibrosis.

00:16:42.333 --> 00:16:47.038
<v Lauren Martz>It's not entirely clear if that's because of the organ that you're targeting in that place.

00:16:47.072 --> 00:16:54.812
<v Lauren Martz>The liver has a big regenerative capacity, um, but I think it's kind of re-energized the field, the idea that you might actually be able to do this.

00:16:55.346 --> 00:16:56.881
<v Lauren Martz>And when you're looking at IPF.

00:16:57.649 --> 00:16:59.650
<v Lauren Martz>The unmet need is so great.

00:16:59.884 --> 00:17:07.593
<v Lauren Martz>People talk about the survival times being comparable to really advanced and aggressive cancers, even with the therapies that we have on the market.

00:17:08.059 --> 00:17:17.301
<v Lauren Martz>One thing that I noticed that I think everyone who's familiar with the field probably knows is that there's not a lot right behind, um, this recent Boehringer approval.

00:17:17.603 --> 00:17:20.939
<v Lauren Martz>BMS has a therapy that's in Phase III that should read out this year.

00:17:21.339 --> 00:17:28.814
<v Lauren Martz>And then there are not too many others at the late stages of development, but the Phase II pipeline is very, very active.

00:17:29.181 --> 00:17:32.151
<v Lauren Martz>So there are more than 20 programs in Phase II.

00:17:33.051 --> 00:17:36.087
<v Lauren Martz>Most of them go against different targets.

00:17:36.121 --> 00:17:38.423
<v Lauren Martz>Most of those targets have first in class potential.

00:17:38.723 --> 00:17:46.131
<v Lauren Martz>And so what we don't know right now is whether these new targets, new mechanisms that people are applying to IPF.

00:17:46.999 --> 00:17:53.771
<v Lauren Martz>will have, you know, a safe, a safety or efficacy advantage over everything else, but we will get a wave of proof of concept data.

00:17:54.673 --> 00:17:56.407
<v Selina Koch>Lauren for the, oh, sorry.

00:17:57.041 --> 00:18:00.244
<v Stephen Hansen>So, Lauren, I just wanted to know about those programs that are in the Phase II testing.

00:18:00.244 --> 00:18:18.497
<v Stephen Hansen>Do, do we have any sense as to how many of those fit into this prior bucket of mechanisms that you might expect to slow progress but not halt it, versus what might actually be, getting at that, being able to fully stop fibrosis progression, or even reverse it?

00:18:18.497 --> 00:18:20.932
<v Stephen Hansen>Do, do, do we have any sense of how, how those split out?

00:18:21.599 --> 00:18:29.575
<v Lauren Martz>So I don't know that we have actual numbers on that, and I think every company that you speak to is probably going to say that they think that their therapy can halt fibrosis.

00:18:30.142 --> 00:18:37.415
<v Lauren Martz>Um, so one of the problems with the, the three approved therapies, I, I think from what I've heard, is a therapeutic index issue.

00:18:37.682 --> 00:18:44.990
<v Lauren Martz>So what happens with pulmonary fibrosis specifically is there's a injury to the lung, which can happen over time.

00:18:44.990 --> 00:18:51.630
<v Lauren Martz>It can be persistent or, or maybe an acute thing that triggers an inflammatory and a pro fibrotic cascade.

00:18:52.431 --> 00:19:03.142
<v Lauren Martz>That eventually  activates and expands fibroblasts and ends up creating this extracellular matrix that, you know, the fibrosis that, um, damages cells and makes the organs not work.

00:19:03.741 --> 00:19:15.053
<v Lauren Martz>So a lot of the strategies that have been tested, and there have been a lot of Phase III failures in this indication, kind of hit the top of that cascade or, you know, try to dampen this entire process.

00:19:15.053 --> 00:19:17.321
<v Lauren Martz>But the problem is this is needed for normal wound healing.

00:19:17.522 --> 00:19:19.991
<v Lauren Martz>It's needed for a lot of normal cellular, processes.

00:19:20.424 --> 00:19:23.127
<v Lauren Martz>So toxicity has a big, been a big issue.

00:19:23.194 --> 00:19:29.701
<v Lauren Martz>So there's that therapeutic index issue where maybe if you could, get the right target, get the right dose.

00:19:29.800 --> 00:19:34.306
<v Lauren Martz>it might not be, the mechanism itself is not correct for, you know, stopping this process.

00:19:34.705 --> 00:19:49.188
<v Lauren Martz>So a lot of these companies are going downstream or targeting just a piece, you know, one of the arms of these really complex pathways or trying to sort of dampen the amplification signals, for example.

00:19:49.520 --> 00:20:00.231
<v Lauren Martz>Again, there's been a lot of Phase II success that hasn't translated to Phase III, I think there are just a lot of open questions about what will work, and some of the trials aren't that long either.

00:20:00.231 --> 00:20:09.942
<v Lauren Martz>So something that shows sort of an initial burst in lung function over the first four months or three months may not actually end up being a long-term solution.

00:20:09.942 --> 00:20:13.644
<v Lauren Martz>So, a lot of translational problems in, in this indication.

00:20:14.346 --> 00:20:16.347
<v Selina Koch>So Lauren, what you were saying earlier was super interesting.

00:20:16.347 --> 00:20:25.457
<v Selina Koch>Like if you hit that cascade at the very top and you shut down the entire fibrotic mechanism, you can probably guess that you'll have some efficacy, but then you have this therapeutic window issue.

00:20:25.923 --> 00:20:46.211
<v Selina Koch>And then if you hit one of the arms of the complex pathway downstream, I guess, which was what you're saying people are, are doing now, is this a case where we're gonna learn about which specific pathways are sort of redundant and can be replaced by another easily and which are kind of fundamental to the disease process through clinical trial work?

00:20:47.078 --> 00:20:48.247
<v Lauren Martz>I think that's the hope.

00:20:48.380 --> 00:20:51.849
<v Lauren Martz>Um, there's a, a lot of talk about how redundant these pathways are.

00:20:51.849 --> 00:20:56.121
<v Lauren Martz>There's a lot of crosstalk interplay between the pathways too.

00:20:56.121 --> 00:21:04.328
<v Lauren Martz>So one target isn't necessarily just in one arm of these pro fibrotic signaling pathways or pro-inflammatory signaling pathways.

00:21:04.930 --> 00:21:24.849
<v Lauren Martz>the way I'm looking at it, and I, I don't know if this is how everyone's looking at it, but I think as these Phase II results, proof of concept results come out, we should sort of maybe get a better understanding of which parts of this pathway are more fundamental to, the pathology and IPF in particular and, and maybe other fibrotic diseases as well.

00:21:24.849 --> 00:21:28.487
<v Lauren Martz>There's quite a bit of talk about how, you know, this has been.

00:21:29.253 --> 00:21:37.528
<v Lauren Martz>Sort of an entry point for some companies into fibrotic diseases because there is a lot of overlap in how these pathways work across the different organs.

00:21:37.762 --> 00:21:47.571
<v Lauren Martz>It's not perfect to overlap, you know, there are different targets are more active in, different disease settings, but, it's a very active area of science where the learnings can definitely translate.

00:21:48.307 --> 00:22:02.820
<v Selina Koch>For the biology geeks out there, Lauren did diagram some of this biology in her story and point out six different sort of intervention points that companies are, are looking at Sophie and, and map the targets to those, to those intervention points.

00:22:02.820 --> 00:22:05.222
<v Selina Koch>So if you're interested, check out her, uh, story.

00:22:06.958 --> 00:22:12.763
<v Stephen Hansen>Lauren, any chance you can give us a little preview or taster of the next fibrosis story that you're gonna be coming out with?

00:22:13.498 --> 00:22:13.898
<v Lauren Martz>Sure.

00:22:13.898 --> 00:22:14.532
<v Lauren Martz>Thanks Steve.

00:22:14.665 --> 00:22:31.148
<v Lauren Martz>So I spoke with, the head of Boehringer's discovery team for  inflammatory and respiratory diseases to get a sense of how a leader in the IPF and fibrosis drug development field is thinking about the next wave of technologies.

00:22:31.415 --> 00:22:35.886
<v Lauren Martz>So we'll have a, a Q and A story come out based on that conversation, which was really interesting.

00:22:36.188 --> 00:22:41.759
<v Lauren Martz>And that is kind of looking beyond the fibroblasts and myofibroblast cell types that we hear so much about.

00:22:42.126 --> 00:22:48.200
<v Lauren Martz>And they're really focusing on the alveolar cells and regenerating, you know, the cells that are injured in this process.

00:22:48.432 --> 00:22:59.478
<v Lauren Martz>and I'm also looking at the new discovery methods and new modalities that are being applied to fibrosis, not IPF specifically, just more broadly.

00:22:59.478 --> 00:23:07.652
<v Lauren Martz>So the idea that if we move beyond the small molecules that have been such a focus here and use different modalities or different ways of thinking about treating this.

00:23:07.652 --> 00:23:17.996
<v Lauren Martz>Maybe actually, you know, getting rid of the fibrosis, degrading that or different, completely different ways of thinking about treating this type of pathology might be possible.

00:23:17.996 --> 00:23:21.333
<v Lauren Martz>So this is the, the very early stage, research in the field.

00:23:22.901 --> 00:23:23.300
<v Stephen Hansen>Very cool.

00:23:23.300 --> 00:23:24.001
<v Stephen Hansen>Well, thanks Lauren.

00:23:24.001 --> 00:23:25.604
<v Stephen Hansen>That sounds like super interesting stuff.

00:23:25.703 --> 00:23:30.142
<v Stephen Hansen>as Selina's noted, you can check out Lauren's story on fibrosis at BioCentury.com.

00:23:31.076 --> 00:23:33.211
<v Stephen Hansen>Yeah, really looking forward to the rest of stuff that's coming out too.

00:23:33.545 --> 00:23:34.011
<v Stephen Hansen>Appreciate it.

00:23:34.846 --> 00:23:45.891
<v Stephen Hansen>Um, so Selina, now I'm gonna come to you, cause I think as most people, if you've listened to this podcast long enough, you've probably know that Selena's a pretty big fan of psychedelics, on the podcast.

00:23:46.191 --> 00:23:51.028
<v Stephen Hansen>So, um, why don't you kind of fill us in on the latest clinical update, from last week.

00:23:51.596 --> 00:23:52.130
<v Selina Koch>Thanks, Steven.

00:23:52.564 --> 00:24:00.939
<v Selina Koch>Well, maybe I'll actually take a step back and say, when we were doing our big catalyst package in January, looking for what are the clinical readouts, the big milestones coming this year.

00:24:01.338 --> 00:24:05.309
<v Selina Koch>We noticed that 26 is gonna be catalyst rich for the psychedelic space.

00:24:05.509 --> 00:24:19.324
<v Selina Koch>So just very briefly, you know, I wanna say the headline news there, right came last month with Compass Pathways announcing it had met its endpoint and a Phase III trial for treatment resistant depression for a psilocybin analog.

00:24:19.825 --> 00:24:29.267
<v Selina Koch>So that was its second positive Phase by the end of this year, they hope to submit an NDA, and this may be the next regulatory test, for a psychedelic at FDA.

00:24:29.601 --> 00:24:31.068
<v Selina Koch>They were able to raise some money on that.

00:24:31.502 --> 00:24:43.714
<v Selina Koch>After the Lykos sort of debacle in PTSD, um, depression is the lead indication for psychedelics and there are two other companies that expect Phase III data this year.

00:24:43.882 --> 00:24:54.459
<v Selina Koch>The other two, Cybin, well now, which is now known as HELUS, and Mindmed, which is now known as Definium, a lot of rebranding after the Lykos thing.

00:24:55.026 --> 00:24:58.797
<v Selina Koch>But both, um, one has a psilocybin analog, one has an LSD analog.

00:24:58.997 --> 00:25:00.365
<v Selina Koch>Those are coming in the second half.

00:25:00.699 --> 00:25:00.932
<v Selina Koch>Okay.

00:25:01.465 --> 00:25:05.537
<v Selina Koch>But then since then, we've also had a couple of earlier stage readouts.

00:25:05.537 --> 00:25:12.443
<v Selina Koch>So the one last week was from Cybin HELUS, not for its lead in depression.

00:25:12.777 --> 00:25:17.249
<v Selina Koch>But for a, different program in Phase II for generalized anxiety disorder.

00:25:17.249 --> 00:25:22.319
<v Selina Koch>So this is another indication with sort of a cluster of activity from different kinds of psychedelics.

00:25:22.787 --> 00:25:34.465
<v Selina Koch>And so this is for a DMT type compound, which, like, LSD and psilocybin is highly psychoactive and hallucinogenic, but it's shorter acting is kind of its advantage.

00:25:34.732 --> 00:25:39.938
<v Selina Koch>and what was interesting about this one is the company reported that it met its endpoint.

00:25:40.505 --> 00:25:50.248
<v Selina Koch>In these patients who are highly refractory to treatment, long time, like at least 10 years post-diagnosis, not well controlled on the their standard of care therapies, right?

00:25:50.248 --> 00:25:51.282
<v Selina Koch>So tough indication.

00:25:52.017 --> 00:25:55.019
<v Selina Koch>They met the endpoint, at the, primary analysis.

00:25:55.019 --> 00:25:59.490
<v Selina Koch>And then I think there was 67% room remission at six months.

00:25:59.891 --> 00:26:04.395
<v Selina Koch>So there's some durability there, and yet the company shares fell 34% that day.

00:26:04.461 --> 00:26:04.762
<v Selina Koch>Right?

00:26:05.230 --> 00:26:15.874
<v Selina Koch>So the question is, you know why, and you can never be a hundred percent sure why, but when I was looking into the way this trial was designed, it is kind of an interesting one.

00:26:15.874 --> 00:26:22.180
<v Selina Koch>So, so psychedelic studies are notoriously hard to control because these compounds are so powerfully psychoactive.

00:26:22.580 --> 00:26:25.683
<v Selina Koch>You pretty much know if you're in the treatment group or the placebo group, right?

00:26:25.983 --> 00:26:33.191
<v Selina Koch>And so one design that companies are taking and that FDA has suggested is to use an active comparator.

00:26:33.791 --> 00:26:39.330
<v Selina Koch>And so  in some cases what that means is you wanna use a lower dose of your therapeutic compound that.

00:26:40.097 --> 00:26:47.005
<v Selina Koch>It just meets the threshold for being perceptible, but is not projected to be therapeutic.

00:26:47.071 --> 00:26:54.179
<v Selina Koch>So if you can separate a little bit some of those, um, side effects from the efficacy, then that's what they're trying to do.

00:26:55.079 --> 00:27:08.192
<v Selina Koch>And that is how this company positioned, this, messaged this trial design all along until they had the Phase II data and then they ended up just pooling the two dose groups because they performed identically.

00:27:08.692 --> 00:27:14.865
<v Selina Koch>When you have functional unblinding and people can guess which dose group you're in, and you have something like a psychedelic.

00:27:15.532 --> 00:27:17.501
<v Selina Koch>Where there's a lot of high expectations.

00:27:17.501 --> 00:27:22.339
<v Selina Koch>People, you know, there's a lot of mainstream media covers that suggest, these are like massive breakthroughs, right?

00:27:22.840 --> 00:27:25.943
<v Selina Koch>Um, you can, it can inflate your efficacy.

00:27:26.310 --> 00:27:29.413
<v Selina Koch>And so there's kind of like three possibilities now, right?

00:27:29.413 --> 00:27:30.448
<v Selina Koch>Like Yeah.

00:27:30.781 --> 00:27:37.888
<v Selina Koch>Functional and blinding and expectation bias are really driving the efficacy here or the low dose is actually effective.

00:27:38.589 --> 00:27:42.594
<v Selina Koch>or something else, you know, small studies are noisy and you just, you know.

00:27:42.661 --> 00:27:54.806
<v Selina Koch>I can't always like get a good read, but it just means that that paradigm, it has a mark against it now because we didn't come out with like really clear dose response and there was no placebo arm.

00:27:55.105 --> 00:27:56.508
<v Selina Koch>So you can't compare against that either.

00:27:57.608 --> 00:28:02.247
<v Stephen Hansen>This is kind of, as you mentioned, this is kind of a chronic problem and this is something that they'll always have to deal with, right?

00:28:02.247 --> 00:28:08.019
<v Stephen Hansen>I mean, is how you try and blind these studies without having that immediate functional unblinding,

00:28:08.385 --> 00:28:08.952
<v Selina Koch>Yeah.

00:28:09.019 --> 00:28:13.023
<v Selina Koch>You blind them by everybody knowing, knowing, quote unquote, that they're in the treatment arm.

00:28:13.023 --> 00:28:13.290
<v Selina Koch>Right.

00:28:13.657 --> 00:28:15.359
<v Stephen Hansen>Mm. Right, right.

00:28:15.527 --> 00:28:16.326
<v Stephen Hansen>Well, really interesting.

00:28:16.361 --> 00:28:20.999
<v Stephen Hansen>Uh, Selina, you know, appreciate the, uh, you know, I'm sure you'll, you'll, you'll stay on top of this, I have no doubt.

00:28:21.098 --> 00:28:21.665
<v Selina Koch>I will.

00:28:23.233 --> 00:28:35.880
<v Stephen Hansen>Um, but you, you know, you mentioned the catalyst and, uh, you know, I sort of had a similar, I guess, scenario in that, we published the, uh, 2026 Obesity Catalyst, uh, story, uh, about a month, a month ago.

00:28:36.647 --> 00:28:42.019
<v Stephen Hansen>And we've also already had a couple milestones kind of drop that we, that we'd been sort of, uh, projecting were were coming.

00:28:42.252 --> 00:28:44.855
<v Stephen Hansen>And so I just kind of wanted to quickly highlight two of those.

00:28:45.256 --> 00:28:47.826
<v Stephen Hansen>So the first one was from Novo.

00:28:47.959 --> 00:28:57.669
<v Stephen Hansen>this was the redefined four study that was a head-to-head of their CagriSema, amylin GLP-1, uh, versus Lilly's, uh, Zepbound tirzepatide.

00:28:58.236 --> 00:29:14.219
<v Stephen Hansen>So this was the study that Novo was really hoping would separate them from Lilly and sort of give them the opportunity to be able to launch pretty strongly if they showed, you know, some meaningful, at least as good as if not better than, you know, than than Lilly's drug.

00:29:14.586 --> 00:29:16.887
<v Stephen Hansen>And then, you know, hopefully you're a bit better on safety.

00:29:17.221 --> 00:29:21.659
<v Stephen Hansen>Unfortunately probably could not have gone worse, for Novo, I think.

00:29:21.759 --> 00:29:29.901
<v Stephen Hansen>Um, they essentially paid millions of dollars to conduct a study that I would guess Lilly would probably want to put on their own label.

00:29:30.134 --> 00:29:39.144
<v Stephen Hansen>So the 84 week study showed that CagriSema patients lost 23% of their weight versus 25 and a half percent for the high dose Zepbound.

00:29:40.310 --> 00:29:45.950
<v Stephen Hansen>Essentially it kind of, it ran into the same problems that Novo saw with their redefined one study, the first Phase III for CagriSema.

00:29:47.218 --> 00:29:55.626
<v Stephen Hansen>In which protocol allowed for dose modification, so that meant, uh, some patients didn't reach, or sustain their highest CagriSema dose.

00:29:56.027 --> 00:30:03.000
<v Stephen Hansen>The study was open label, uh, that just relates to the fact that CagriSema requires this sort of dual chamber device.

00:30:03.167 --> 00:30:04.469
<v Stephen Hansen>it can't be intermixed.

00:30:04.469 --> 00:30:09.807
<v Stephen Hansen>And so you kind of already knew you couldn't blind it because of the device that was gonna be used.

00:30:10.141 --> 00:30:20.652
<v Stephen Hansen>You had this situation where, you know, patients were basically knowing if they were getting the investigational drug or if they were getting a drug that they've probably heard all about on TV commercials and radio ads.

00:30:20.852 --> 00:30:22.953
<v Stephen Hansen>You know, especially if you live in the U.S. with Zepbound.

00:30:23.453 --> 00:30:31.895
<v Stephen Hansen>So, you know, it, it, it's hard to say how much that really confounded sort of the outcome there, but it was kind of a big disaster for Novo.

00:30:31.962 --> 00:30:37.402
<v Stephen Hansen>I mean, this basically, uh, investors wiped out 26 billion market cap in late February.

00:30:37.836 --> 00:30:48.046
<v Stephen Hansen>And it really now, you know, CagriSema was Novo's opportunity to kind of try and regain some of the obesity market that they had been sort of losing to Lilly.

00:30:48.746 --> 00:30:56.354
<v Stephen Hansen>And I think this is gonna be a pretty big setback in terms of their timeline as to when they have their next opportunity to kind of regain that market share.

00:30:56.753 --> 00:31:09.933
<v Stephen Hansen>Cause it just seems hard to see how CagriSema is gonna be able to launch later this year and really dent, you know, Lily's tirzepatide franchise, which is kind of on a rocket ship up as things stand.

00:31:10.234 --> 00:31:15.073
<v Stephen Hansen>Just really quickly, you know, the next big opportunity Novo's probably gonna have is with zenagamtide.

00:31:15.240 --> 00:31:16.807
<v Stephen Hansen>it's formerly known as amycretin.

00:31:17.275 --> 00:31:19.143
<v Stephen Hansen>But that's just started Phase III testing.

00:31:19.210 --> 00:31:24.915
<v Stephen Hansen>Uh, you know, so while they haven't given any guidance on data or regulatory submissions yet, you know, I think the best guess.

00:31:25.549 --> 00:31:29.053
<v Stephen Hansen>That readouts are in late 2027, maybe early 2028.

00:31:29.721 --> 00:31:32.624
<v Stephen Hansen>And so you're probably not, you know, looking at a launch till 2029.

00:31:32.757 --> 00:31:36.728
<v Stephen Hansen>And in the meantime, you know, oral therapies are gonna get more established.

00:31:36.728 --> 00:31:43.367
<v Stephen Hansen>You're probably gonna have injectables on the market that have once monthly, maybe more infrequent dosing.

00:31:43.468 --> 00:31:47.771
<v Stephen Hansen>So it, it's just, it's gonna be a different market by the time that program reaches there.

00:31:47.771 --> 00:31:50.375
<v Stephen Hansen>So not a great position for Novo to be in right now.

00:31:50.375 --> 00:32:01.085
<v Stephen Hansen>The other one I just wanted to highlight was from last week, Zealand Pharma and Roche, announced, Phase II data for their amylin program, petrelintide, as a monotherapy.

00:32:01.352 --> 00:32:02.921
<v Stephen Hansen>Now the markets hated this one as well.

00:32:03.721 --> 00:32:05.690
<v Stephen Hansen>Um, Zealand was down 37%.

00:32:06.391 --> 00:32:25.777
<v Stephen Hansen>on the news and, part of that, I think some of that comes down to, just in my personal opinion, I think some of that comes down to messaging, kind of the same trap that Novo fell into with CagriSema, in that, you know, I think Zealand had kind of been suggesting that they could get maybe mid upper teens in terms of weight loss for this therapy.

00:32:26.144 --> 00:32:30.580
<v Stephen Hansen>What they did show was placebo adjusted weight loss of 9% at 42 weeks.

00:32:30.815 --> 00:32:40.357
<v Stephen Hansen>so that's not far off from what we saw with like a GLP-1 with Wegovy, but it's about half of what Lilly showed with eloralintide at 48 weeks.

00:32:40.692 --> 00:32:45.663
<v Stephen Hansen>So in terms of efficacy, still a lot to be desired there for, for the Zealand program.

00:32:46.163 --> 00:32:50.000
<v Stephen Hansen>You know, I think it definitely fell short of expectations on that side.

00:32:50.367 --> 00:32:57.107
<v Stephen Hansen>But I don't think the data's nearly as bad as maybe the investors are making out, primarily because of the safety data that they reported.

00:32:57.442 --> 00:33:14.625
<v Stephen Hansen>So, you know, on a placebo adjusted basis, you have to remember all of these incretin therapies, you know, all the obesity therapies that we've seen so far, GI tolerability has always been the main primary issue, and just keeping patients on drug has been the main issue, especially in real, real world setting.

00:33:15.192 --> 00:33:17.194
<v Stephen Hansen>So on a placebo adjusted basis.

00:33:17.729 --> 00:33:33.510
<v Stephen Hansen>They basically showed no vomiting, no diarrhea, no constipation across the entire trial, for the petrelintide treated patients, nausea was about 13%, whereas the pooled data for eloralintide showed about 20% on nausea.

00:33:34.211 --> 00:33:41.184
<v Stephen Hansen>And treatment discontinuation rates, uh, for adverse events were actually lower for treated patients than they were for placebo.

00:33:41.752 --> 00:33:47.025
<v Stephen Hansen>So it was a pretty stellar data set with regard to tolerability.

00:33:47.525 --> 00:34:02.073
<v Stephen Hansen>I guess the reason why I am more optimistic about that, despite the efficacy that was shown there was because I think when you think about the obesity population, I think there's a large group of people that would be more than happy to lose 10 to 15% of their weight.

00:34:02.472 --> 00:34:12.150
<v Stephen Hansen>And if you can offer them something that doesn't have the GI side effects, so you're gonna be able to keep patients on therapy much longer than what we typically observe with GLP-1 therapies.

00:34:12.182 --> 00:34:17.320
<v Stephen Hansen>As I mentioned, I think that real world experience is about 80% of patients discontinue within one year.

00:34:17.588 --> 00:34:25.963
<v Stephen Hansen>And the problem with that is then you have this cycling effect where people can then regain that weight and typically you're regaining more fat than you are muscle.

00:34:25.963 --> 00:34:28.965
<v Stephen Hansen>And so it can be this really bad, cycle that you can go into.

00:34:29.367 --> 00:34:43.047
<v Stephen Hansen>I think anything that offers the opportunity to lose the weight that patients want, and if you have a tolerability profile that will keep them on therapy, and prevent that rebound, you know, I think that's a pretty compelling commercial proposition.

00:34:43.280 --> 00:34:45.182
<v Stephen Hansen>Again, quite early Phase II data.

00:34:45.615 --> 00:34:51.188
<v Stephen Hansen>but yeah, I, I think it'll be interesting to see, to see how they adjust as they move into, as they move into Phase III.

00:34:52.090 --> 00:34:54.759
<v Selina Koch>I know it's too early really to think about commercial dynamics.

00:34:54.759 --> 00:35:07.070
<v Selina Koch>But I do wonder if  if the sweet spot for it would be the like second line, you know, if the, just thinking of like the psychology of the patient or whatever, if they just initially think, oh I just wanna go for the one, then I'm gonna lose weight fast, you know?

00:35:07.070 --> 00:35:10.907
<v Selina Koch>But then they hit those GI issues that makes so many people go off drug.

00:35:11.242 --> 00:35:12.844
<v Selina Koch>They're like, is there anything else?

00:35:12.844 --> 00:35:14.211
<v Selina Koch>Like, can I try with anything else?

00:35:14.244 --> 00:35:15.445
<v Stephen Hansen>that, that's, that's an interesting one.

00:35:15.445 --> 00:35:15.545
<v Stephen Hansen>Yeah.

00:35:15.545 --> 00:35:24.155
<v Stephen Hansen>For, for for the, for the group of patients who don't make it through the first month or something like that and don't actually get much weight loss because they just can't tolerate it.

00:35:24.188 --> 00:35:25.755
<v Stephen Hansen>If they're like, oh, is there something else I could try?

00:35:25.755 --> 00:35:27.824
<v Stephen Hansen>And they're like, yeah, well there's one that doesn't have any of those problems.

00:35:27.824 --> 00:35:29.360
<v Stephen Hansen>You just might not lose as much.

00:35:30.027 --> 00:35:31.929
<v Stephen Hansen>That might be a pretty compelling opportunity.

00:35:31.929 --> 00:35:35.867
<v Stephen Hansen>And, and I should mention just very quickly, just because, uh, it just came up today.

00:35:36.833 --> 00:35:38.302
<v Stephen Hansen>Also in connection with amylin.

00:35:38.369 --> 00:35:46.244
<v Stephen Hansen>AbbVie announced today their first Phase I data for ABBV-295 which is their amylin that they licensed from Gubra last year.

00:35:46.376 --> 00:35:48.012
<v Stephen Hansen>That showed about nine and a half percent.

00:35:48.012 --> 00:35:52.650
<v Stephen Hansen>So a little bit more than what Zealand showed in placebo adjusted a weight loss.

00:35:52.650 --> 00:35:54.385
<v Stephen Hansen>But that was after just 12 weeks.

00:35:54.619 --> 00:35:57.788
<v Stephen Hansen>That looks to be much more in line with maybe what we saw from Lilly.

00:35:58.155 --> 00:36:02.126
<v Stephen Hansen>But what we didn't see and what they didn't give any detail on was the AE profile.

00:36:02.326 --> 00:36:17.574
<v Stephen Hansen>So I think that'll be sort of one of the very interesting dynamics, I think in amylin is sort of how much you push for efficacy versus how much you optimize for that tolerability profile that differentiates it from another incretin therapy.

00:36:17.942 --> 00:36:22.346
<v Stephen Hansen>Yeah, still plenty more to come, I'm sure from amylin and other mechanisms in obesity.

00:36:22.480 --> 00:36:24.681
<v Stephen Hansen>Think that's all we have time for today.

00:36:25.016 --> 00:36:43.634
<v Stephen Hansen>So please do check out our latest episode of our sister podcast, The BioCentury Show, where I had a delightful chat with SoftBank, Jackie Fok about the future of AI in biopharma, the opportunity for life sciences in the U.K. and the importance of broadening representation across our industry.

00:36:43.900 --> 00:36:44.869
<v Stephen Hansen>Thanks for joining us.

00:36:45.235 --> 00:36:46.403
<v Stephen Hansen>We'll see you next week.

00:36:46.836 --> 00:36:50.407
<v Stephen Hansen>Kendall Square Orchestra provides the music for BioCentury this week.

00:36:50.708 --> 00:37:02.887
<v Stephen Hansen>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.