Ep. 339 - Biotech M&A, In Vivo CAR Ts & FDA Tumult

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<v Jeff Cranmer>Fueled by cancer, obesity, and cardiovascular deals billion dollar plus takeouts in biotech are on the rise, we'll take a closer look on the latest BioCentury's This Week podcast.

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<v Jeff Cranmer>Plus, welcome to ASH Monday, data have been pouring out of Orlando from the Hematology Society's Annual Meeting, we'll zero in on first-in-human in vivo CAR T data from Kelonia.

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<v Jeff Cranmer>And more data, another Praxis win provides much needed progress in rare genetic epilepsies.

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<v Jeff Cranmer>And Selina got that data she was looking for the full data set for semaglutide, uh, presented at CTAD, semaglutide was supposed to quench CNS inflammation, it didn't, Selina will dig into the details for you.

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<v Jeff Cranmer>And another tumultuous week at FDA, Steve will give his analysis on the back half of the podcast.

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<v Jeff Cranmer>I'm Jeff Cranmer, one of the executive editors here at BioCentury, and joining me today are my colleagues.

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<v Simone Fishburn>Simon Fishburn, Editor in Chief.

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<v Selina Koch>Selina Koch, Executive Editor.

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<v Lauren Martz>Lauren Martz, Executive Director of Biopharma Intelligence.

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<v Steve Usdin>And Steve Usdin, Washington Editor.

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<v Jeff Cranmer>It is back, BioCentury's indispensable, J.P. Morgan Guide has returned.

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<v Jeff Cranmer>Visit jpmguide.com for the inside track on sideline events, and receptions happening during the annual biotech kickoff in San Francisco.

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<v Jeff Cranmer>And hey, if you're hosting something special, use the online form that you'll find there to make sure you event appears in our guide.

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<v Jeff Cranmer>Again, that's jpmguide.com to make the most of your JPM 2026 week.

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<v Jeff Cranmer>There's a couple of big movers on data today, uh, Structure Therapeutics, obesity companies shares doubling in value as its once daily oral therapy leads to 11% weight loss and Kymera rises 50% on strong biomarker results for its STAT6 degrader for moderate to severe atopic dermatitis.

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<v Jeff Cranmer>Both companies gaining billions in market caps, Stephen Hansen will have analysis of structure's data on BioCentury.com.

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<v Jeff Cranmer>So, hey, let's kick things off with a month remaining, this year's already tied for the most billion dollar plus M&A deals of any year in the past 10.

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<v Jeff Cranmer>Selina, what's behind the trend?

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<v Selina Koch>Yeah, well M&A has certainly been a bright spot, people keep citing.

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<v Selina Koch>So we just do what we do here and wanted to quantify that.

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<v Selina Koch>So by the end of November, so is not yet full year data, so there could be more, um, there were $37 billion plus M&A deals announced this year time 2025 to 2021 for the biggest year in the last decade.

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<v Selina Koch>And so we broke it down a couple ways, we broke it down by disease area and we broke it down by,  the stage of the lead product of the company being acquired.

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<v Selina Koch>It probably won't surprise anybody that, you know, companies with marketed products are the biggest set within that 37.12  but more interestingly, maybe there were six takeouts this year, if a billion dollars or more for companies in Phase I. That's up from two last year, one the year before zero in 2016, 2017.

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<v Selina Koch>And even three preclinical companies were taken out for a high price tag.

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<v Selina Koch>And this sort of Lindsay's analysis coincided with the perspective piece written by our colleague, Paul Bonanos, who had noticed a couple of these, you know, big money takeouts of early stage companies and had just posed the question, you know, with pharma patent cliffs looming and a limited number of say mature assets available for M&A, you know, are we gonna start seeing buyers pay more, for early stage companies?

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<v Selina Koch>And, you know, Lindsay's data suggests that maybe that's already starting to happen.

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<v Simone Fishburn>Yeah, I mean, I think it's really important because a lot of the focus when people talk about M&A is on, on consolidation of the big companies.

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<v Simone Fishburn>And you know, we've been talking for a couple of years about looking at this rise of sort of billion dollar plus deals, where  there's a lot of value in the, you know, let's say $1 to $5 billion range and a lot of companies and assets and you know, what you're talking about, Selina is also,  you know, regarding the patent cliff.

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<v Simone Fishburn>Well, we know that a lot of the later stage assets have been picked off, right?

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<v Simone Fishburn>So companies now need to go a little bit earlier in the value chain.

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<v Simone Fishburn>And, you know, they're still willing to put considerable weight behind some of those bets that are obviously riskier.

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<v Simone Fishburn>Obviously we've got the J&J takeout of Halda for over $3 billion, which is a preclinical company, I think that raised a lot of eyebrows.

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<v Simone Fishburn>But I think also maybe you could talk a little bit about the breakdown of therapeutic area that Lindsay's piece sort of laid out.

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<v Selina Koch>Yeah.

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<v Selina Koch>Um, well, cancer remains King.

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<v Selina Koch>Um, if you look at the last decade's worth of.

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<v Selina Koch>These really large M&A deals, it's just a, the slope is just upward and to the right, with 2025 being the decade's highest number, um, at 20 of them.

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<v Selina Koch>For all the hotness that has been, I&I, the last three years have been really steady for these large takeouts, at like 7 to 10.

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<v Selina Koch>And then the other growth area, of course, obesity and cardiovascular seeing sort of year over year increases.

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<v Selina Koch>Recently

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<v Simone Fishburn>Yeah.

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<v Simone Fishburn>Well, you know, I obviously for companies and in particular their investors, this is a good exit path given that the IPO market is still very constrained.

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<v Simone Fishburn>So I guess we are gonna imagine the, the beat of $1 billion plus M&A deals is probably gonna carry on for a little while into 2026.

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<v Jeff Cranmer>All right.

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<v Jeff Cranmer>Yeah, and that number as uh, Selina, said earlier, that's $9 billion plus M&A deals year to date, for companies whose lead programs were in preclinical testing or Phase I at the time the deal was announced and that to the most in 10 years.

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<v Jeff Cranmer>Okay, ASH, uh, unavoidable.

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<v Jeff Cranmer>If you have an email inbox, I'm sure a lot of ASH emails have landed in your lap.

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<v Jeff Cranmer>Uh, this week, ASH will deliver more first-in-human in vivo CAR T data that once again showcases the promise of the modality and justifies the growing pipeline.

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<v Jeff Cranmer>There's new data coming from Kelonia Therapeutics.

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<v Jeff Cranmer>They show that three more patients have achieved MRD negativity after treatment with an in vivo CAR T cell therapy.

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<v Jeff Cranmer>my colleague Lauren tells me that the questions now include how long can the near perfect track record last, which technologies will prove safest and most effective, and how will these results translate to autoimmune diseases.

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<v Jeff Cranmer>Let's bring in Lauren, now, uh, Lauren, you gonna answer all those questions?

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<v Lauren Martz>Thanks, Jeff.

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<v Lauren Martz>I certainly don't have all of those answers, but with each clinical readout, I do think we get a little bit closer.

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<v Lauren Martz>As you mentioned, at a high level, what we've learned from the latest clinical readout for in Vivo CAR T, is that Kelonia's KLN-1010 a lentiviral vector in vivo CAR T cell therapy targeting BCMA, is that it led to MRD negativity one month after treatment for all three heavily pretreated multiple myeloma patients evaluable in that study.

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<v Lauren Martz>We also know from the abstract that at least one of the patients remains MRD negative at three months, and we should learn more tomorrow when the full data are presented.

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<v Lauren Martz>I think another important thing about this readout is that this was profiled as a late breaker at ASH, which says a lot about how much excitement exists around in vivo CAR T cell therapies right now.

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<v Lauren Martz>We'll have a story tomorrow once the full data are reported.

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<v Lauren Martz>And for that I've been looking into the pipeline of in vivo CAR T cell therapies.

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<v Lauren Martz>And right now, you know, we were able to find nearly 40 programs, and this is what BioCentury's has been able to identify.

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<v Lauren Martz>And that I think just reflects a ton of growth that's happened over the last few years.

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<v Selina Koch>So Lauren, looking across the pipeline, um, what are the other ones that have, you know, reported data and importantly, I guess, durability data.

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<v Lauren Martz>Yeah, Selina, I think durability is, is the biggest question, and I'm not sure how much data we have to support that yet.

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<v Lauren Martz>Um, when AstraZeneca bought EsoBiotec, we knew that they had efficacy data from four patients, I don't think there's much information about how durable the effects are, and in that case, again, it was a lentivirus targeting BCMA.

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<v Lauren Martz>I think that just remains a big unanswered question, and that will help.

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<v Lauren Martz>You know, I think that will have a big impact on where this technology ultimately ends up being used as well.

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<v Lauren Martz>So durability seems to be very important when you're treating cancers.

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<v Lauren Martz>It may not be as important for, um, autoimmune applications of in vivo Car Ts.

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<v Lauren Martz>And the autoimmune applications are a bit farther behind, but I think we are starting to see some of the very early clinical proof of concept in those as well.

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<v Jeff Cranmer>Okay.

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<v Jeff Cranmer>Thank you for that, Lauren.

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<v Jeff Cranmer>Uh, looking forward to seeing that one too.

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<v Jeff Cranmer>Other readouts, as I mentioned at the top, Praxis, and Novo's Alzheimer's data for semaglutide, let's start there.

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<v Jeff Cranmer>We discussed the readout on last week's podcast, data again at the clinical trials on Alzheimer's Disease Meeting.

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<v Jeff Cranmer>Selina, you are eager to see the full data.

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<v Jeff Cranmer>What did you learn?

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<v Selina Koch>Yeah, so the days leading up to the US holiday of Thanksgiving, we just learned that Semaglutide did not slow progression, but we didn't see an y outcomes or the biomarkers?

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<v Selina Koch>So this, in terms of a full data set, I mean, Novo had the data for like two weeks before the CTAD meeting, so it's top line.

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<v Selina Koch>They didn't do a bunch of subgroup analyses or anything like that, but they showed the, the various clinical scales, the primary endpoint, CDR sum of boxes is pretty standard for Alzheimer's.

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<v Selina Koch>And then there's a bunch of other standard clinical functional rating scales.

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<v Selina Koch>And probably the most striking thing is that the curves, over time of the treatment group and the placebo group are really just exactly on top of each other.

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<v Selina Koch>There's no argument for a trend toward benefit, or anything like that.

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<v Selina Koch>Really, it was a very clear failure.

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<v Selina Koch>And is, Much as we hate to see failures, um, 'cause they're not good for patients.

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<v Selina Koch>At least the data were clear in that regard.

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<v Selina Koch>The hypothesis though, right, so you always have to ask yourself, okay, but did the drug do what it was supposed to do?

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<v Selina Koch>And the hypothesis was that, semaglutide was gonna decrease peripheral inflammation, which was in turn going to decrease neuroinflammation.

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<v Selina Koch>And that was going to be the mechanism by which it was gonna help patients.

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<v Selina Koch>You have to, you know, measure all of those things to get a sense of whether or not it ameliorated peripheral uh inflammation.

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<v Selina Koch>It measured high sensitivity C-reactive protein.

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<v Selina Koch>That is what it measured, Novo measured in CLOTS trials, it's cardiovascular outcomes trials, for example.

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<v Selina Koch>And that was reduced about 30% as was expected.

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<v Selina Koch>Um, but that was the only really, that was the extent of the characterization of peripheral inflammation.

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<v Selina Koch>Um, and there was just a big bucket of neuroinflammation markers.

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<v Selina Koch>And apart from one small change on one of them, they were just not changed.

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<v Steve Usdin>So that, that brings up the question that I had, which is did you have to test a huge number of patients to learn that it didn't move the needle on these key biomarkers?

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<v Steve Usdin>Couldn't they have figure that out with, I don't know, a dozen patients or 20 patients.

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<v Selina Koch>They absolutely could have done that work with fewer patients.

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<v Selina Koch>Yes.

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<v Simone Fishburn>And, and Selina did write that last week.

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<v Simone Fishburn>But I also feel like Selina, they kind of underpowered this.

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<v Simone Fishburn>'Cause when you wrote that piece of, they could have done it, you know what Steve is talking about, very important, you know, how you're using your patients.

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<v Simone Fishburn>But you pointed to the fact that they would learn a lot from this.

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<v Simone Fishburn>And I'm sort of really wondering how much they did learn from this because it was underpowered and maybe power is the wrong word

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<v Selina Koch>Power's the wrong word.

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<v Selina Koch>We're only like, we're only like 3,800 patients here.

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<v Simone Fishburn>Yeah.

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<v Simone Fishburn>So, so power's the wrong word, but it was, it was not well designed really to get at the peripheral information because it only had this one very crude marker of C-reactive protein, right?

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<v Simone Fishburn>Even though they had multiple markers in the brain.

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<v Selina Koch>Yeah.

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<v Simone Fishburn>Cause it had gotten into the brain, they'd have been full of data and like, oh, it, it increases this marker, but not that marker.

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<v Simone Fishburn>But they didn't really do a very rigorous job of understanding which part of the peripheral inflammation pathways, it, it was activating.

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<v Simone Fishburn>So how do you feel like in terms of the design and what you're able to walk away with?

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<v Selina Koch>I feel like the mechanistic piece, even though there were a lot of biomarkers, was a little underdeveloped.

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<v Selina Koch>Yeah, I agree with that.

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<v Selina Koch>Like if I thought, okay, there's some crosstalk between the periphery and the central immune systems, I would wanna know, what are the candidate pathways for mediating that crosstalk specifically, and that's not c-reactive protein, right.

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<v Selina Koch>That's a general all purpose tool, and not thought to act directly, at that interface of the blood-brain barrier.

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<v Selina Koch>You might imagine doing a smaller more focused study, testing those specific hypotheses of how those that communication might happen across the blood brain barrier, which really wasn't done.

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<v Selina Koch>Another idea for how the periphery can influence central inflammation is by the blood brain barrier integrity kind of breaking down and peripheral immune cells getting in.

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<v Selina Koch>They did have a few, um, two I think biomarkers of blood brain barrier integrity, and those were unchanged by semaglutide.

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<v Simone Fishburn>So Selina, what I'm kind of hearing is that this molecule didn't really get into the brain very well, right?

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<v Selina Koch>Yeah, so that's an outstanding question.

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<v Selina Koch>The, the, the thought is based on the, you know, preclinical data and other data that's available that it probably doesn't get into the brain at any appreciable amount.

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<v Selina Koch>Novo did do a small study like in conjunction with the Phase III trials rather than before.

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<v Selina Koch>Um, which was also presented at CTAD.

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<v Selina Koch>In, in 8 out of 10 people there was a small amount of semaglutide in the cerebral spinal fluid after semaglutide treatment um, at, oh, I wanna say maybe a 10th of a nanogram per liter or something like that.

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<v Selina Koch>So far less than you're saying in the plasma and strangely did not seem to correlate with the level in the plasma.

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<v Selina Koch>So in Peter Johannsen  who talked about that said very specifically, look, even if small amounts get into the CSF, it's a very different question whether or not any of that penetrates into the brain parenchyma in any appreciable amount.

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<v Simone Fishburn>Okay, so let me go back to Steve's question now, or Steve's point, which is you do this trial on 3000 plus patients.

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<v Simone Fishburn>You don't think you might do a little bit more work on whether the molecule gets in the brain.

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<v Selina Koch>I know, I know there, there are things that could have been done before jumping into a nearly 4,000 patient Phase III trial, especially given the precious resource that patients are for trials.

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<v Jeff Cranmer>Let's jump to some good news.

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<v Jeff Cranmer>shares of Praxis Precision Medicines rose 31% on Friday after a Phase II/III study of the company's sodium channel modulator for a couple of subtypes of developmental and epileptic  encephalopathy, was stopped early for efficacy.

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<v Jeff Cranmer>Stock is still moving up today.

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<v Jeff Cranmer>These came out of the American Epilepsy Society Annual Meeting, uh, the full data came out Saturday.

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<v Jeff Cranmer>Uh, Lauren, there's a small molecule, why is that significant?

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<v Jeff Cranmer>I know,  the seizures that they were evaluating are associated with a high risk of autism spectrum disorders.

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<v Jeff Cranmer>Um, what did you learn in writing this story?

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<v Lauren Martz>I think the fact that this is a small molecule is one of the things that makes this data so, exciting for Praxis, and, and just for the field.

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<v Lauren Martz>This developmental and epileptic encephalopathy, is specifically genetic form caused by mutations in SCN2A and SCN8 A and here we have a small molecule that can treat specifically the genetic form of this disease.

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<v Lauren Martz>You know, it's been a particularly difficult year to advance cell and gene therapies through the clinic.

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<v Lauren Martz>When you look at the pipeline for these types of DEEs, a lot of the development is focused in cell and gene therapies, uh, gene therapies in particular.

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<v Lauren Martz>And so just given the commercial hurdles and some of the safety issues.

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<v Lauren Martz>I think it's just a good reminder that  with the advances that we're seeing in small molecule drug development, there is an opportunity in some cases, to design drugs that can treat these kinds of genetic disorders.

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<v Lauren Martz>And then the other thing that I think is really interesting here is that there's an autism, a genetic autism component involved here as well.

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<v Lauren Martz>So this is, you know, a trial that's focused on epilepsy associated with these mutations.

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<v Lauren Martz>But SCN2A, for example, is also one of the most well characterized genetic risk factors for autism.

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<v Lauren Martz>I think progress in helping restore function of the sodium channel could have an impact on autism.

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<v Lauren Martz>And, and this is definitely a hot area for  drug development for different reasons right now.

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<v Selina Koch>Yeah, probably worth pointing out, in this era of really tough funding for gene therapies, it's the safety issues we've seen this year, the continued commercial challenges.

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<v Selina Koch>That modality piece is probably really important, and it's not the first, you know, we saw Roche kind of prove this.

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<v Selina Koch>That a small molecule can come into a space where there's antisense and gene therapy and, and kind of outcompete, that was Evrysdi in spinal muscular atrophy.

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<v Simone Fishburn>Yeah, but I, I think that's, you know, both of these things are sort of converging on real actual steps within autism.

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<v Simone Fishburn>Obviously there's a lot of noise political, that part of the program we'll get to after the break, I guess, Jeff, in terms of the politics around these things.

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<v Simone Fishburn>But this is obviously about epilepsy, which is a feature of some autism spectrum disorders.

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<v Simone Fishburn>But I think that there's a belief that  there may also be benefits for some of the cognitive let's say features or other features of autism.

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<v Simone Fishburn>And I think really what I'm trying to say is this is generally good news, not only for the epilepsy part of it, but also for the idea that with genetics and with these various approaches, there is progress being made maybe slowly, but progress being made within autism.

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<v Simone Fishburn>Is that how you look at it?

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<v Lauren Martz>Yeah, Simone, that is how I see it.

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<v Lauren Martz>And I think it's also important to note that this EMBOLD Study, that was stopped early, specifically looked at seizure reduction endpoints in the clinic for clinical efficacy.

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<v Lauren Martz>But Praxis Precision Medicines is also running a second registrational study.

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<v Lauren Martz>That is looking at DEEs unrestricted, um, you know, not limited to the these specific mutations.

00:20:27.625 --> 00:20:33.598
<v Lauren Martz>And in that study they are looking at different efficacy endpoints more broadly.

00:20:34.031 --> 00:20:40.939
<v Lauren Martz>Some of those are related to symptoms that may be more relevant to other aspects of autism spectrum disorders.

00:20:41.940 --> 00:20:42.840
<v Selina Koch>I think that's gonna be key.

00:20:42.840 --> 00:20:50.749
<v Selina Koch>And the other thing is if you treat very, very early, right, so these carry with them these genetic defects, a risk of developing autism.

00:20:51.115 --> 00:20:57.756
<v Selina Koch>So I wonder if we would see, you know, in the real world data some day, a decrease in that risk.

00:20:58.589 --> 00:21:06.832
<v Jeff Cranmer>All right, we're gonna cut to a quick break, all of those stories you'll find on BioCentury.com, BioCenturypodcast.com.

00:21:06.865 --> 00:21:12.403
<v Jeff Cranmer>If you like what you're hearing like, and subscribe to BioCentury This Week.

00:21:12.637 --> 00:21:19.810
<v Jeff Cranmer>We'll be back to talk about a wild week in Washington with our Washington Editor, Steve Usdin.

00:21:20.345 --> 00:21:25.017
<v Alanna Farro>BioCentury This Week is brought to you by The 5th East-West Biopharma Summit in South Korea.

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00:22:07.959 --> 00:22:11.128
<v Jeff Cranmer>We are back on the BioCentury This Week podcast.

00:22:11.329 --> 00:22:13.065
<v Jeff Cranmer>Let's get to Washington.

00:22:13.065 --> 00:22:14.165
<v Jeff Cranmer>Steve, I think.

00:22:14.398 --> 00:22:24.308
<v Jeff Cranmer>You had a personal best in the number of reports that you filed last week and where to begin?

00:22:24.875 --> 00:22:37.855
<v Steve Usdin>Well, I think that when we left, listeners to the podcast last week, uh, Richard Pazdur was still the the Director of the Center for Drug Evaluation and Research at FDA.

00:22:38.323 --> 00:22:49.968
<v Steve Usdin>There was, uh, some level of concern around a memo that Vinay Prasad, the Director of CBER, had written about, vaccine policy and, and a new framework for vaccine regulation.

00:22:50.535 --> 00:22:55.140
<v Steve Usdin>And things have, look, we've had another, another turn on the, on the rollercoaster.

00:22:55.507 --> 00:22:58.410
<v Steve Usdin>And this one is, uh, you know, kind of a barrel roll.

00:22:58.410 --> 00:23:07.986
<v Steve Usdin>So first, Richard Pazdur announced his retirement starting at the end of December, so he was on the job less than three weeks, and then he left.

00:23:08.286 --> 00:23:25.836
<v Steve Usdin>Almost every living Former FDA commissioner signed onto a commentary that was published in the New England Journal of Medicine warning that FDA's new vaccine policies constitute a public health crisis and expressing broader concerns about Commissioner Marty Makary's management of the Agency.

00:23:26.270 --> 00:23:40.919
<v Steve Usdin>And then Tracy Beth Høeg was named Acting CDER Director to replace, um, Richard Pazdur, who for the next few weeks, has gone back to being head of the Oncology Center of Excellence.

00:23:41.486 --> 00:23:52.864
<v Steve Usdin>So you could hear the gasps from life sciences executives around the country and around the world when they heard that Richard Pazdur was retiring as CDER director.

00:23:53.265 --> 00:24:02.540
<v Steve Usdin>And then you could hear the phones hitting the floor when they started getting the texts announcing that Tracy Beth Høeg had been named Acting CDER Director.

00:24:03.107 --> 00:24:12.250
<v Steve Usdin>So the short form she's viewed inside FDA and among regulated industry, as unqualified for the job and an ideologue.

00:24:12.550 --> 00:24:17.888
<v Steve Usdin>She's likely to provoke a wave of resignations at FDA, that's what I'm hearing from people in the Agency.

00:24:18.355 --> 00:24:21.526
<v Steve Usdin>And I think, greater uncertainty for drug developers.

00:24:21.826 --> 00:24:33.137
<v Steve Usdin>Her appointment and Pazdurs departure or as imminent departure, I think are signs that drug reviews are going to be influenced by political pressures and ideological influences.

00:24:33.771 --> 00:24:35.707
<v Simone Fishburn>Just a minute before we get to Dr.

00:24:35.707 --> 00:24:38.042
<v Simone Fishburn>Høeg as the head of CDER.

00:24:38.175 --> 00:25:00.365
<v Simone Fishburn>Steve, you know, we've been running a survey, which is now closed and we'll be getting that out this week from the survey responses, here's a heads up to everybody from the survey responses as well as from a lot of personal interactions and conversations that we had at various meetings last week with biopharma VCs, biotech heads.

00:25:00.699 --> 00:25:09.540
<v Simone Fishburn>There was really a feeling that Pazdur's appointment was the biggest stabilizing force for FDA, you know, he was the grownup in the room kind of thing.

00:25:09.807 --> 00:25:11.876
<v Simone Fishburn>Most of all I think is the stability.

00:25:11.876 --> 00:25:22.386
<v Simone Fishburn>Now, his departure has certainly got a lot of people very worried about next year, even before they knew who the next CDER Director would be, right.

00:25:22.653 --> 00:25:30.161
<v Simone Fishburn>What is there in terms of, have you got any good news, Steve, upside calming things that you can tell people out there?

00:25:30.895 --> 00:25:32.663
<v Steve Usdin>From FDA, there's no good news.

00:25:32.931 --> 00:25:38.470
<v Steve Usdin>I think there's, there's news that people interpret as the possibility of good news, right.

00:25:38.470 --> 00:25:41.673
<v Steve Usdin>So, you know, we've talked about it on the, on the podcast before.

00:25:41.873 --> 00:25:56.288
<v Steve Usdin>There's, this Plausible Mechanism Pathway, which, leaving aside the name of it, has the potential to unlock the development of therapies for very rare conditions and bespoke therapies for very rare conditions.

00:25:56.621 --> 00:26:01.125
<v Steve Usdin>But it is far from certain that it's gonna be implemented in a way that actually does that.

00:26:01.125 --> 00:26:04.563
<v Steve Usdin>But if you're looking for good news, you know, there's a potential there.

00:26:05.262 --> 00:26:32.156
<v Steve Usdin>There's also, something else that happened last week, which was that one, one of the things that's been in the works at FDA for some time is an idea that Commissioner Marty Makary and CBER Director Vinay Prasad have of putting out a statement saying that the default assumption at FDA going forward will be that companies will have to perform a single clinical trial, single pivotal clinical trial to support drug approval.

00:26:32.457 --> 00:26:41.967
<v Steve Usdin>They had been trying to get a statement saying that through HHS Legal Office for some time, and hadn't been able to get final sign off on it.

00:26:42.366 --> 00:26:49.106
<v Steve Usdin>Commissioner Makary discussed it, basically leaked the memo, um, to a reporter from another publication last week.

00:26:49.307 --> 00:26:55.180
<v Steve Usdin>So it's been in the news quite a bit, but the, the press release still hasn't been released, so we don't know exactly what's in it.

00:26:55.646 --> 00:27:00.117
<v Steve Usdin>And what's more, we don't know how FDA might put it into practice.

00:27:00.518 --> 00:27:03.855
<v Steve Usdin>So you could look at that as good, you could look at it as bad.

00:27:04.021 --> 00:27:06.758
<v Steve Usdin>It's certainly going to create a great deal of uncertainty.

00:27:07.157 --> 00:27:13.230
<v Steve Usdin>You know, translating a, a press release into predictable policy is going to be challenging.

00:27:14.199 --> 00:27:16.768
<v Simone Fishburn>So what are your expectations?

00:27:16.768 --> 00:27:19.604
<v Simone Fishburn>What do we need to know about Dr. Høeg

00:27:20.204 --> 00:27:24.942
<v Steve Usdin>So she is an MD, specializing in sports medicine, she has a PhD in epidemiology.

00:27:25.609 --> 00:27:27.244
<v Steve Usdin>She is never run a clinical trial.

00:27:27.278 --> 00:27:28.813
<v Steve Usdin>She's never reviewed a drug.

00:27:29.146 --> 00:27:31.415
<v Steve Usdin>She has no regulatory experience whatsoever.

00:27:31.883 --> 00:27:36.153
<v Steve Usdin>She rose to prominence as a COVID contrarian, during the pandemic.

00:27:36.755 --> 00:27:45.096
<v Steve Usdin>She advised Florida Surgeon General Joseph Ladapo on anti-vaccine policies that have been heavily criticized by public health experts.

00:27:45.529 --> 00:27:52.971
<v Steve Usdin>She's played a leading role as FDA's representative to the ACIP that's the CDC's Advisory Committee on immunization practices.

00:27:53.570 --> 00:28:01.413
<v Steve Usdin>And which, in her capacity there, she's  challenged the need for mandatory vaccination of children.

00:28:01.613 --> 00:28:08.553
<v Steve Usdin>She's called for changes to the vaccine schedule that will result in American children receiving fewer vaccines.

00:28:09.220 --> 00:28:17.194
<v Steve Usdin>As a Senior Advisor to FDA Commissioner Makary, Høeg's been closely involved with the Commissioner National Priority Voucher Program.

00:28:17.561 --> 00:28:24.568
<v Steve Usdin>She's close to CBER Director, Vinay Prasad, and helped write a memo, the one that I mentioned earlier, uh, announcing new vaccine policies.

00:28:24.803 --> 00:28:37.281
<v Steve Usdin>Last week, every living FDA Commissioner except one Stephen Hahn, signed a commentary that was published by the New England Journal of Medicine that condemned that memo saying it will have disastrous consequences for vaccine development, and public health.

00:28:37.582 --> 00:28:54.499
<v Steve Usdin>People I know who have interacted with Høeg at FDA, say she's scientifically curious um, in meetings she asks probing questions or wants to get into the details, but they also say that she's an advocate, not a regulator, that she starts with conclusions and cherry picks data to get to the desired response.

00:28:54.833 --> 00:29:03.641
<v Steve Usdin>Uh, and the FDA staff I've spoken with say Høeg has used that, that approach, and she's used observational data in ways that aren't scientifically appropriate.

00:29:03.974 --> 00:29:05.876
<v Steve Usdin>To make assertions about drug safety.

00:29:06.111 --> 00:29:15.619
<v Steve Usdin>One example, she was in charge of a review of COVID vaccines that led to restrictions that were posed by longtime scientists and civil servants at FDA.

00:29:16.054 --> 00:29:28.465
<v Steve Usdin>Phil Krause, the Former Deputy Head of Vaccines at FDA, and Luciana Borio, the Former Acting FDA Chief Scientist, wrote a commentary that we published in BioCentury, about the actions that Høeg took on COVID vaccines.

00:29:28.833 --> 00:29:41.479
<v Steve Usdin>And they wrote that shifting standards and late stage demands for new data based on faulty scientific assumptions have eroded trust, delayed access to important tools, and discourage developers from advancing vaccine innovation.

00:29:42.146 --> 00:29:51.321
<v Steve Usdin>I think we can expect that Høeg's gonna move on MAHA priorities, restricting access to, SSRIs and other psychiatric drugs for adolescents.

00:29:51.655 --> 00:29:58.061
<v Steve Usdin>Taking action to reduce access to puberty blockers, supporting access to psychedelics.

00:29:58.363 --> 00:30:04.335
<v Steve Usdin>And, and other, other steps I think that are, you know, on the MAHA agenda, that's what we can expect that she's gonna do.

00:30:04.803 --> 00:30:11.075
<v Jeff Cranmer>Steve, I'm just curious, has Bill Cassidy made any comments about what's been happening at FDA?

00:30:11.910 --> 00:30:23.020
<v Steve Usdin>So you're, you're referring to Senator Cassidy, who's the Chairman of the Senate Health Education Labor Committee, he has made, public statements about the ACIP.

00:30:23.587 --> 00:30:35.066
<v Steve Usdin>He's really kind of apoplectic, about what ACIP has done, in terms of reducing access of newborns or recommendations for newborns to get access to hepatitis B vaccines.

00:30:35.232 --> 00:30:43.441
<v Steve Usdin>It's a field that, Cassidy knows well, he's a physician, and he treated a lot of  hepatitis B patients.

00:30:43.441 --> 00:30:47.010
<v Steve Usdin>And he's extremely concerned about what ACIP has done.

00:30:47.311 --> 00:30:50.914
<v Steve Usdin>I haven't heard him say anything publicly about FDA.

00:30:51.816 --> 00:30:52.217
<v Simone Fishburn>Steve.

00:30:52.217 --> 00:30:58.288
<v Simone Fishburn>Well, I think, you know, we would agree more with the orthodoxy on vaccines than let's say on the MAHA agenda.

00:30:58.623 --> 00:30:59.757
<v Simone Fishburn>And I understand that Dr.

00:30:59.757 --> 00:31:04.362
<v Simone Fishburn>Høeg has sort of had a lot to say about the COVID vaccines.

00:31:04.461 --> 00:31:07.865
<v Simone Fishburn>Also acknowledging that there are many people with different views about that.

00:31:08.333 --> 00:31:14.605
<v Simone Fishburn>How relevant do you think her COVID vaccine position is gonna be in her role as the Head of CDER?

00:31:14.939 --> 00:31:16.708
<v Simone Fishburn>Is there daylight between those?

00:31:17.575 --> 00:31:23.213
<v Steve Usdin>Well, she doesn't regulate vaccines at CDER, CDER doesn't regulate vaccines.

00:31:23.548 --> 00:31:41.398
<v Steve Usdin>But I think that what it shows is how she thinks about things, and the fact that, she's willing, and eager really to take actions and to take regulatory actions based on ideological principles rather than, the, uh, scientific consensus.

00:31:41.833 --> 00:32:01.853
<v Steve Usdin>She's also acting, and this is consistent with what Marty Makary has been doing as FDA Commissioner, in the absence of public advisory committees or other forms that would create transparency and accountability around FDA's actions on topics that affect public health and the health of individual patients.

00:32:02.252 --> 00:32:05.323
<v Steve Usdin>Not to mention the ability of companies to develop drugs.

00:32:06.057 --> 00:32:09.626
<v Jeff Cranmer>Steve, a few other things are on the agenda in Washington.

00:32:09.626 --> 00:32:16.134
<v Jeff Cranmer>I don't know how much is gonna get done, we've been talking a lot about the comeback of the Biosecure Act.

00:32:16.200 --> 00:32:17.602
<v Jeff Cranmer>Um, where does that stand?

00:32:18.102 --> 00:32:28.913
<v Steve Usdin>So, uh, the Biosecure Act, has been included in the House version of the National Defense Authorization Act, the NDAA, which is a must pass bill.

00:32:29.012 --> 00:32:31.281
<v Steve Usdin>It's a bill that's gonna be passed very soon.

00:32:31.548 --> 00:32:36.988
<v Steve Usdin>It's almost certain that Biosecure 2.0 will be included in the bill.

00:32:37.288 --> 00:32:39.790
<v Steve Usdin>People may remember, we've talked about this on the podcast.

00:32:40.124 --> 00:33:00.510
<v Steve Usdin>The new version of Biosecure differs from the version that was pending last year because rather than listing specific companies, it creates a process for the Administration right now, the Trump Administration to determine whether companies are so-called biotechnology companies of concern.

00:33:00.711 --> 00:33:08.586
<v Steve Usdin>And for those companies there will be restrictions on US companies or companies that wanna sell their products in the U.S. Accessing their services.

00:33:08.586 --> 00:33:20.832
<v Steve Usdin>There's a five-year grandfathering period and there's also limits on  the effectiveness of the, of the sanctions, the effect of the sanctions on the ability of companies to sell drugs in the United States.

00:33:21.031 --> 00:33:28.239
<v Steve Usdin>A lot is gonna depend on how the law is interpreted or implemented by the, the Trump Administration.

00:33:28.705 --> 00:33:45.690
<v Steve Usdin>Another bill that's almost certain to be included in the NDAA is something called the Fight China Act, which imposes sanctions on certain Chinese entities and restricts or requires notification of US investments in specified high risk technologies in China.

00:33:46.190 --> 00:33:49.493
<v Steve Usdin>Basically it establishes an outbound investment screening regime.

00:33:50.094 --> 00:34:04.842
<v Steve Usdin>It isn't directly targeted at biotech, and in fact, there are provisions in it that, that kind of provide a carve out for certain research activities that are conducted in China, but nonetheless, it's likely to impact of biotech companies.

00:34:05.209 --> 00:34:34.672
<v Steve Usdin>Again, a lot of it's gonna depend on how the Trump Administration interprets it, but some kinds of collaboration, some kinds of investments, in companies in China that, use, uh, advanced chipsets, for example, that are developed in China or use advanced AI systems that are Chinese systems, could be, subject to notification requirements or even have to disinvest in in projects in China, depending on how the act is interpreted by the Administration.

00:34:35.539 --> 00:34:41.079
<v Jeff Cranmer>Okay, uh, you can read all of Steve's stories, BioCenturypodcast.com.

00:34:41.344 --> 00:34:43.581
<v Jeff Cranmer>We will be back next week.

00:34:43.581 --> 00:34:47.018
<v Jeff Cranmer>Don't forget to subscribe to BioCentury This Week.

00:34:47.318 --> 00:34:52.690
<v Jeff Cranmer>And check out the latest from our sister podcast The BioCentury Show.

00:34:52.690 --> 00:34:58.563
<v Jeff Cranmer>Selina sat down with Bill Hinshaw to talk precision medicine.

00:34:58.795 --> 00:35:02.733
<v Jeff Cranmer>Bill is CEO of Fore Biotherapeutics.

00:35:03.233 --> 00:35:07.672
<v Jeff Cranmer>Kendall Square Orchestra provides the music for BioCentury This Week.

00:35:07.905 --> 00:35:20.117
<v Jeff Cranmer>The group connects science and technology professionals and other members of the Greater Boston community to collaborate innovate and inspire through music, while supporting causes related to healthcare and education.