Latest / BioSpace / Capricor’s DMD therapy still alive, Merck/Moderna’s cancer vax shines, FDA’s future revealed
Transcript
- Jef: Hello, and welcome to Biospaces the Weekly. I'm your host, Jeff Axt. Today we have some updates on Capricor therapeutics for you. This week, the FDA granted an extension for the review of Capricor's cell therapy for Duchesne Muscular Dystrophy. Meanwhile, an unhappy shareholder is advocating for change after the company announced a pause to all other pipeline programs. We also have positive news from Merck and Moderna on their personalized mRNA-based cancer vaccine that could help both companies. Moderna certainly needed this phase three win as it looks ahead to its post-COVID business. And Merck, of course, is staring down the loss of exclusivity of its blockbuster immunotherapy Keytruda. Over at the FDA, President Donald Trump has nominated the next permanent commissioner, White House aide Heidi Overton. So we'll get some reactions around that announcement. And finally, checking in on the ever-popular oral weight loss space. Eli Lilly launched Foundado in the UK this week. While Novo Nordisk has started trialing lower doses of its Wagovy pill. The two weight loss rivals are doing everything they can to capture more of the market. Let's get started. Hi guys, good to see you. Heather: Hi. Annalee Armstrong: Hello. gabby: Bye. Jef: How is everybody feeling this week? Heather: Good. It's gabby: Pretty good. Heather: it's Jef: I see some hesitation there, not running on all cylinders. gabby: Yes. Heather: well, it's pumpkin spice latte release day Starbucks, so right here. Yeah. mean Annalee Armstrong: Yeah. Heather and I ran out of course this morning already. Jef: There you go. I think that August might be a little bit early for pumpkin spice Heather: we got the I got the muffins. gabby: Bye bye. Jef: lattes for me, but I do love the fall and I'm very excited that we are nearing ever so closer to it. Heather: Okay, Annalee Armstrong: Yes. Heather: you can have one next week, gabby: best season. Heather: next Tuesday. No, it's just September first, so you know. Yeah. Yeah, yeah. Jef: Is it official next Tuesday is fall? No way. Not till September. Okay. Got it. you mean next Tuesday for the podcast? Yes. We'll have a pumpkin spice latte special. Annalee Armstrong: No. Heather: Yes. I'll wear orange. Jef: Did you guys see that study this week? I was just thinking when you guys were kind of slow to answer and feeling a little tired. Heather: Hmm. Jef: A study came out in PNAS this week that you could either exercise for twenty minutes or nap for ninety minutes to get a little boost to your memory. I was like, I'll take the exercise. That sounds way more efficient. Heather: isn't it after a third being awake for 30 hours though? I'm a little concerned I might trip off the treadmill. Jef: Fair. gabby: Yeah, I'm not working out after 30 hours of not sleeping. Heather and I were saying, don't know if I've ever gone Annalee Armstrong: But but gabby: 30 hours without sleeping. Annalee Armstrong: It I Heather: Mm-hmm. Annalee Armstrong: I certainly have in recent times being a mom of young kids, gabby: Mm-hmm. Heather: Mm. Annalee Armstrong: but I will always, always choose the nap. I love napping. It is my favorite pastime, besides gardening. Jef: I feel like napping is never effective. I wake up more tired than when I went to sleep. Heather: That's I I've heard gabby: Same, I'm not even a napper and I'm choosing napping over exercising. Jef: Okay. Annalee Armstrong: ha. Heather: I've read another study that said if you so you've all heard of the ten minute nap. So if you take a ten minute nap, it's apparently it's a maximum of twenty minutes before you're gonna get that sleep hangover. Before like if Jef: Hm. Heather: you if you fall asleep for an hour and then wake up, then you're gonna be really tired. But if you sleep for twenty minutes, you're gonna Yes, kind of scope. Jef: So cat naps is where it's at. Annalee Armstrong: My My grandma used to say that you don't need a nap. You just need to lay down for ten minutes and have three or four good yawns. So she would just like lay down on her couch, Heather: Ha ha Annalee Armstrong: yawn a few times and be like, Okay, ready to go. Jef: That seems like such a grandparent thing to say. I'm just resting my eyes. Heather: I'll try it. Yeah. Annalee Armstrong: Yeah. Yeah. gabby: What I do when I really need a nap is I drink a cup of coffee and then sleep for 30 minutes. And then when you wake up, the coffee is supposed to have kicked in. Yeah. Jef: Coffee hits? Heather: Interesting. Huh. Jef: That is clever. I like it. All right. Well, on that note, since we're all energized talking about that, let's get into introductions and start our show. Annalie, Heather: Yeah. Lots of ideas. Mm-hmm. gabby: You Jef: why don't you start us off this week? Annalee Armstrong: Yeah, I'm Annalie Armstrong, senior editor at Biospace, and I do the weekly Biofarm Executive newsletter, which hits your inboxes every Wednesday morning. Jef: Thank you. And Heather? Heather: I'm Heather Mackenzie, senior editor at Biospace and I curate Clinica Space, which hits your inboxes bright and early Monday mornings. Jef: And Gabby. gabby: And I'm Gabrielle Mason, a senior editor with Biospace, and I curate our manufacturing brief, which goes out every Tuesday, and then our daily newsletter, Gene Pool. Jef: All right. And once again, I'm Jeff Axed, managing editor, and with that, we'll dive in. So starting with Capricor, I mentioned we have a couple of updates here for you. but just a little bit of background first, as a reminder, the company has been trying to get its cell therapy for DMD across the finish line since last year, and it received its first rejection in July and then resubmitted and accepted and the FDA accepted that application with a PADUFA date this past weekend. Things were not looking great for Capricor, however, after last month's adcom. So late last month the adcom committee voted against the therapy's approval. and so now the FDA has granted an extension. Heather, you've been covering this. fill us in on the latest. Heather: Yeah, this is I was saying to somebody the other day, this story is probably the biggest roller coaster I have ever covered. so so yeah, on on Friday we were watching for this decision to potentially come down because if a Padufa day is set on a weekend, it's usually supposed to be the Friday. so Friday, Saturday, and Sunday passed without any news from Capricor or the FDA. And then on Monday The company announced a three month extension to the review to so that the FDA will have a chance to review twenty-four month open label extension data and analysis supporting what Capricor called a refined proposed indication. so the previous indication, which an FGA advisory committee voted nine to three against last month, as Jeff was mentioning, was cardiomyopathy associated with Jashan. The new proposed indication, upper limb function, was actually the phase three trial's primary endpoint. Jef: didn't Capricorn previously try to change that endpoint to the the cardio one, the left ventricular ejection fraction? Heather: They did. and that is interesting. it was probably a good idea since this is an area of extremely high end met need in Duchenne. cardiomyopathy is actually the leading cause of death for these patients. however the the adcom really focused a lot on this endpoint, and neither the FDA nor most of the advisors felt like it was met. so it might be safer at this point. This might be what Capricorn is thinking to focus on upper limb function where the conversation was a little more neutral or a little bit more supportive. So just FYI, Capricorn claims that the Hope 3 trial hit both endpoints, which was LBEF, the cardiac endpoint, was the secondary, and upper limb function was the primary. although the FDA, in its briefing notes before the ADCOM. disagreed with that determination. Jef: Right. Yeah, there was a lot of discussion now about which statistical analysis plan was used. CEO Linda Marbane argued that the FDA had used a draft version of this SAP instead of the updated one. And that if they had used the updated one or any of the updated ones beyond that first draft, that there would have been statistic statistical significance across those endpoints. but with regard to that cardio endpoint, Morbain also pointed out that it was calculated across the full DMD population rather than just in patients with established cardiomyopathy. So that was another point of contention Heather: Yeah, and that that would include the younger patients with with Deshen who likely don't have cardiomyopathy yet, since that that's kind of a a later stage thing. but this Jef: Gotcha, okay. Heather: whole thing is just it's so confusing. I mean I I think for Capricor as well. you know, there's been a lot of lack of communication. They were supposed to have an advisory committee meeting last year, before that decision came down, but that was cancelled. and it was cancelled apparently without Linda Marmaine, the the CEO's knowledge. so she she heard from a lot of very concerned stakeholders after that and didn't know what to tell them. Jef: Yeah, that was back in the absence of adcom FDA days. You know, we had that long hiatus from adcoms, and that was one of the the first to just get lost in the mix. And now adcoms are back and Capricorn had one, but as we said, it didn't quite go their way. So as you said, it's definitely been confusing, been confusing for the company, been confusing for industry watchers, and of course for Capricor investors. And there's one such investor now who is not too happy, penned a letter like late last week to other shareholders calling for a change of board. After the company earlier this month announced it was gonna pause all those other pipeline programs as it really focuses on getting Darum ISL across that regulatory finish line. Heather: Yeah, and I think it I think it's called it it sounds like you could say chaos capital, but I think it's Chaos Capital disagrees. So they disagree with that decision. Chaos calls itself a significant and growing shareholder in Capricor. And in a letter to other Capricor shareholders last week, they said that they want, quote, an immediate meeting, board change, and capital preservation plan, in addition to that more broader pipeline focus. Jef: Yeah, I I could understand that. I mean, it's it's it seems a little risky to put all your eggs in one basket if the basket is Deremia Heather: Mm. Mm. Jef: saw, which is under all this fire. So unclear again whether they're headed for an approval or a rejection. We will watch very closely as we await the next Padofa in a few months. So Heather: Yeah. Jef: obviously a lot going on here. what is your feeling on all this, Heather, for Capricorn and also just for the industry more broadly? Heather: Yeah, well I I had this, you know, thought and so our staff writer, Tristan Manilag, wrote an excellent feature looking at both Capricor Repli Imune at the adcoms and the decisions so far. just a reminder that Replimune did win approval for its advanced melanoma therapy a couple of weeks ago or last week, I can't keep track. but the expert consensus really seemed to be that while the new interim FDA leaders are are working hard to restore transparency and reliability to the agency after a really chaotic year. This doesn't necessarily mean an easier road for drug sponsors. So basically every application will stand on its own. Jef: That makes sense. And as it should, I think what we're really hoping for is better communication. Like you said, there's been challenges with communication on Capricorse file in particular. I think what the industry really wants is that clear expectations, clear guidelines, and clear communication from the FDA. So one thing that would help with that is permanent leadership. And we will get into a little Heather: Yes. Jef: later in the podcast that we do now have a nominee for the next FDA commissioner. So maybe that will help. But let's let's hold off on that discussion. We've got some other news we want to cover first. So moving on now to Moderna's Merck partnered personalized mRNA based cancer vaccine. This is being trialed in combination with Kei Truda for melanoma. And the phase three trial yielded promising results. The companies announced just last week. And it was a really highly anticipated readout and one that came ahead of schedule, which is really good news for the partners. So Merck, as I said in my intro, is of course facing Kei Truda's loss of exclusivity in the coming years. But I would say the data are possibly even more important. Important for Moderna, which has suffered declining revenue from its COVID nineteen vaccine. Sure Enough, the positive readout nearly doubled Moderna's stock the morning of the announcement from the low sixty dollar range to nearly a hundred and twenty dollars a share. Annalee Armstrong: Yeah, so this was some really big news for the R mRNA field, for Merck, for Moderna, as you mentioned, Jeff. so people who took this combination of this personalized cancer vaccine along with Ketruda, who had melanoma, they lived longer without their disease returning, which achieved the trial's primary endpoint of recurrence-free survival. The study also hit a secondary endpoint that looked at how long patients lived without metastatic lesions appearing in other parts of the body. so you know, you mentioned, Jeff, that this was very highly anticipated, but kind of interestingly, investors really did not put a lot of stock in this program. They were waiting for these results, but they were pretty sure they were going to be negative, which is pretty incredible. so this was a great day for Moderna. But Merck also had an awesome day at the markets because of this. Their shares rose 12%, which is a very, very steep rise for a pharma of their size. And as you mentioned, Merck is kind of eyeing its future after Key Trude, which is going off patent. I believe that patent starts to that patent cliff starts to arrive in about 2028. They have been doing some work to try to extend that. They've got a new formulation out and that kind of thing. But Keychrita is really running its course after, you know, probably a decade or more of dominance in cancer. That drug really changed the cancer paradigm, ushering in the immunosology, you know, phase of cancer treatment. So its impact and its medical advancement was just kind of hard to fathom. But it's also sold billions and billions for Merck. It's been one of the top selling drugs of all time. it's kind of slipped in recent quarters behind what Eli Lilly and Novo are doing with their GLP ones. but after this, Merck has been trying to build that future. They've been doing a lot of investments in ADCs, they have a Trop 2 directed ADC. but really investors were were still kind of unclear on that picture post-Kitruda. So when this trial hit as as positively as it did, this really galvanized investors. They're very excited now. Analysts now predict that intosmirin, which is the name of this cancer vaccine, could be worth peak sales of $2 billion just for the melanoma indication. However, because it's been successful in this trial, they are now even more confident that they're going to see some more positive results in other tumor types. That would bring the peak sale potential to 5.6 billion. billion dollars. Now that would of course be split fifty fifty with Moderna, but that's still a lot of money that investors just were not considering in Merck's future. Jef: Yeah, no, that would certainly help. I think that Keytruda does still have a lead, at least as of twenty twenty-five, for the best-selling drug, but you're right, with those obesity drugs taking up, you know, growing pretty quickly, it will not have that top spot for long. So, and especially with that Annalee Armstrong: Yeah, I I don't I think twenty twenty six it may lose its crown. Jef: Yeah, it'll be interesting to see. But yes, obviously one of the biggest moneymakers for Merck for any pharma, and so they definitely are gonna need the help as that one reaches its patent cliff. Also good news for cancer patients. I mean, we've been covering covering personalized cancer vaccines in a broad scope, you know, back in my basic science days for decades. know, Elaine Martis, one of the pioneers of these vaccines, wrote for us a decade ago. So it's really, really good to see these finally come out. And I th I saw one investor note that said this was the first phase three validation of this approach. And so we do know there are others in the pipeline, and you know, this bodes well for for all of those up up and coming cancer vaccines. So We will keep watching on it and we will see what happens specifically with this Merck and Moderna one that seems to be leading the charge. All right, now getting back to the FDA as promised. So we've been lacking permanent leadership for some time now. Former Commissioner Marty McCary departed the agency in May. The overall sentiment, as we reported, is pretty good under acting commissioner Kyle DiMontes. He he seems to be doing a pretty good job, he and his fellow temporary leaders. both at SEBR and Cedar. There's no permanent leadership across the main review units. They're really working hard to, you know, revitalize the staff and stabilize the agency and rebuild trust among the industry and the public. But industry watchers have nevertheless been eager to learn who might step into that top role on a permanent basis. So we finally have Trump's next nominee. It is White House aide Heidi Overton. What can you guys tell us about her? Annalee Armstrong: So Heidi Overton is currently the deputy director of the White House Domestic Policy Council. She has a medical degree from the University of New Mexico, She did a surgical residency in general surgery at Johns Hopkins, and she has a PhD in clinical investigation from Hopkins, So if Overton were to advance through the nomination process, she would be the third woman ever to lead the FDA. so we'll have to see what happens here. Heather, I know the FDA is totally your wheelhouse. what's been the reaction to this? Heather: Sure, yeah. And and and just just talking about that nomination and and the the confirmation process. I think it was Steven Grossman who said that it's unlikely that this will happen before the midterm elections as Congress is only in session for another, I think, three weeks total, even though it's only almost September. But yeah, so analysts reacting to this news last week, they agreed that the the Trump administration isn't looking to rock what is already a pretty unsteady boat with this nomination. the general consensus is that Overton will be good for psychedelic therapies, a key a key focus of the current administration, obviously, as well as non-opioid pain drugs. this is a bit of a a different one. But Ben Overton wrote a paper in 2017 with former Commissioner McCarry titled Overprescribing is a Major Contributor to the Opioid Crisis. so that was a bit of an interesting read. But analysts say that she is likely to kind of toe the party line, so whatever Secretary Kennedy's thoughts are when it comes to vaccines. Annalee Armstrong: Yeah, and that's really evidenced by the fact that you may have seen her in the background at a few recent White House press conferences, including the one where President Trump announced a directive to split the MMR vaccines. Jef: Yeah. So it looks like, you know, they're not wanting to rock the boat, as you said, with regard to the industry, but maybe also not with regard to the current administration's priorities. She does kind of fall in line with the number of these. the over prescribing thing, interestingly, that was focused on opioids, but it's a similar sentiment to RFKs bent on SSRIs in neuropsychiatric care, pushing against the over prescription, overuse of prescription medications. And that, you know, falls into the psychedelics support category. So definitely seeing a lot of similar themes from her. Heather: Yeah, I sa Yeah. I thought about that when I read that title of the article. I Jef: Mm-hmm. Heather: was like, yeah, that's like the SSRIs and yeah, different yeah, definitely a theme. Jef: Yeah, at a very high level, that is absolutely one of RFK's pushes is to reduce reliance on prescription medications. All right, well, moving on now, let's take a look at the oral obesity market. we know that Novo Nordisk had the head start here. The Wokovi pill was granted FDA approval in December and launched in January. Eli Lilly followed in April with its oral offering, FoundAo. By all accounts, Novo's launch was just spectacular, reached more than 3,000 patients in the first week alone, clearly outpaced Foundado even after Lily's drug hit the market a few months later. Analysts have attributed this in part to name recognition of Vogovi, whereas Lily's pill is an entirely new drug from its GLP1 injectable Zbound. But the big question is, will Lily, excuse me, will Novo be able to retain its lead here and in a way that it couldn't in the injectable space where it had an even longer head start, but Lily eventually overtook it. gabby: Yeah, analysts aren't too sure about the answer to that question, but that definitely won't stop NOVO from trying. The Danish Pharma announced last week that it's launching a phase three study to determine an optimal lower starting dose of the Wigovia pill. Marketing a lower dose Wigovia pill could help NOVO make the product more profitable. One challenge for NOVO is that Wigovia is a peptide. Whereas Lily's Fondeo is a small molecule which is cheaper and easier to manufacture. Jef: Yeah, producing large amounts of that peptide would be hard. And I was looking at the doses, it's pretty astonishing. So patients on oral wagovi take up to 25 milligrams of semaglutide a day. And that's compared with just 7.2 milligrams of semaglutide when it's the injectable. So they need these much larger doses. So that is definitely, you know, biting into the profit there and also just potentially creating more manufacturing challenges. So Nova, of course, off and running to potentially offer lower doses of wagotide. oral Wagovy. But meanwhile, Lily has officially launched Fandeo in the UK this week. gabby: Yeah, and analysts think that this is the best play for Lilly because the market there is price sensitive. So the pharma could potentially be better positioned to outcompete Novo thanks to the high margins of a small molecule therapy. And that's according to a truest analyst who spoke to Biospaces, Tristan Manilak earlier this month. So the drug will initially be only available through private prescriptions, but Lilly is currently working with the National Institute for Health and Care Excellence. Jef: Alright, well we'll continue to watch this race closely. In the meantime, we know there are plenty of other companies hoping to break that novo lily duopoly in the weight loss space. One of those with the pill option in the pipeline and with an a recent readout is NVIDIA, which has been advertising its investigational asset call that they describe as exercise and a tablet. gabby: Yeah, so the phase one readout for Invada, their asset is ENV308, found that healthy adults tolerated the investigational drug pretty well. The biotech didn't share the data specifics behind its claim, but they did say that there weren't any serious adverse events, discontinuations, or dose interruptions recorded. Invada believes the study indicates that the molecule is differentiated from GLP-1 medicines, that We all know they cause nausea, vomiting, and other gut-based side effects. So really going after targeting that GI side effect profile. Jef: So maybe we instead of taking a nap or a little exercise, we pop a pill. Get our energy back. Right. Right. All right. Well, another one that we'll Annalee Armstrong: Yeah. Heather: While napping. gabby: while napping, before the nap, with the coffee. Jef: keep our eye on. and finally always like to end our show with a little peek into Biofarm Executive. Annalie, last week you already teased that there was a special edition on AI coming out this week. what can you tell us about it? Annalee Armstrong: Yeah, so we have been doing obviously a ton of coverage on AI in biotech, how it is rewriting you know, the the deal processes, how big farmers are just so hungry for for partnerships in this area. So we have collected all of our recent coverage into one special edition, which is going to hit inboxes. Well, actually, by the time this podcast is out, it will be in your inboxes. You have to subscribe to that newsletter, Biofarm Executive, which you can do at the top. right corner of our website. And Jeff, correct me if I'm wrong. I believe if you were to subscribe now, if you're not already a subscriber, you would get that special edition sent to you immediately. Jef: Absolutely. And it's the only way to get it right now. It won't be up on our site for another month. So if you want to see the compilation of coverage plus some additional graphics and things that Annalie put together to kind of summarize everything going on in the AI space, definitely subscribe. And as always, subscribe please to this podcast as well. We hope you enjoyed it. Thank you for listening and we'll see you next week.