411: Capricor's data clash and a fugitive in the C-suite

0:16Welcome to this week's episode of The Read Out Loud, a weekly biotech podcast from STAT. I'm Allison DeAngelis. I'm Adam Feuerstein. And I'm Elaine Chen. It's Thursday, July 30th, and on this week's episode, we're going to get an update from Adam on his new side gig as a true crime reporter. He's written another story with new details about the secret biotech life of the Rhode Island fugitive Ronald Fisher. And you know I've got questions. And I have answers. We'll also discuss a setback for Capricorn Therapeutics at an FDA advisory panel meeting and the rest of this week's news. All that after a word from our sponsor.

0:55Thank you.

1:25and secret inner workings of the U.S. healthcare industry. If you're someone who has ever received a medical bill or craves in-depth policy explainers or loves a playful meme now and again, I highly recommend you check this newsletter out. Learn more at the link in this episode's description. And now, back to our regularly scheduled programming. Thanks.

1:46So guys, thanks for helping me out last week. I was ill. Yeah, how high did your fever get last week? It was pretty high. I yeah you were saying Allison Elaine just just take over the podcast do it without me yeah I was kind of I was kind of laid up uh summer summer illnesses are not fun you know it was like a yuck what what really got us was you said I have to keep an open mind yeah and we were like see that's what's happening yeah I was clearly hallucinating Adam's on Death's Door. Yeah, that's how sick I was. Yeah, I was being open-minded about something. Well, we're glad that you're back here.

2:30You've got some news to tell us about out of the true crime segment. But before then, should we get into the biotech, the nitty-gritty from this week? Yeah, let's do it. Okay. So, Serepto Therapeutics officially has a new CEO. On Monday, the company announced that Michael Severino would take over as chief executive. Severino was most recently CEO of Tessera Therapeutics, a gene editing startup founded by Flagship Pioneering, the venture creation firm based right here in Cambridge. This is a big transition for Sarepta. Severino is replacing Doug Ingram, who announced earlier this year that he planned to retire after leading the biotech for nearly a decade.

3:12And he led the biotech during a series of big events, mostly related, almost all related to their development of treatments for Duchenne muscular dystrophy. They got three treatments approved during his time as CEO, but they have faced ongoing questions about how effective those treatments are. The company has also run into regulatory scrutiny over the safety of its gene therapy for Duchenne muscular dystrophy. So Doug Ingram has been helming this company during a really tenuous time. And this is a little bit of an opportunity for Sarepta to turn a new page. Meanwhile, GSK, who also has a new CEO, is making some significant cuts.

4:00The new CEO, Luke Meals, who took over in January, plans to cut about$2.5 billion in costs over the next three years. GSK will be investing more into its late-stage pipeline. The company under Meals now plans to start at least 20 phase 3 trials this year, up from the 10 that I had disclosed at the beginning of the year. Delivering on these plans will be really critical for GSK since it's trying to hit a sales target of$53.2 billion by 2031. And it's doing this while navigating the loss of patent protection on a major HIV franchise. Turning our attention to Washington, D.C., on Wednesday, Anthony Fauci came under fire during a highly anticipated Senate hearing.

4:44The former government health official invoked his Fifth Amendment right to refuse to answer questions about the COVID-19 pandemic and its origins, saying that he was doing so on the advice of his attorneys. Fauci had been subpoenaed to testify before the Senate Homeland Security and Governmental Affairs Committee. That is a panel headed by Senator Rand Paul, who had made no secret of his desire to see Fauci behind bars. Paul has accused Fauci of covering up the origins of the virus that caused COVID, which the senator believes was caused by a lab leak in China and lying to Congress. In one of the highlights of the meeting, or maybe it was a low light, I guess maybe you'd say, Paul ordered Fauci's attorney escorted from the room after the attorney attempted to make a statement to the congressional committee.

5:31All right. Still in D.C., the FDA today is convening advisors to discuss Replimune's investigational skin cancer treatment called RP1. This is a pretty controversial drug. It's the third time that Replimune is seeking FDA approval for this drug. It was initially rejected last year by the FDA's biologics division, which was led at the time by someone we've talked about on this podcast, Vinay Prasad. Stat reported, though, that Prasad played little role in the rejection and that it was instead driven by former top oncology regulator Richard Padser, who questioned the drug's efficacy. After Replimune submitted its application for a second time, the therapy was rejected again this April.

6:16More recently, the White House pushed FDA health officials to examine the drug a third time, according to the Wall Street Journal. So the trial that Repimmune relies on was a single-arm trial testing a combination of RP1 with the PD-1 inhibitor Opdivo in patients who have already tried a PD-1 inhibitor. The FDA argued that the study is not enough to tease out the efficacy of RP1 itself and whether the treatment, which is injected locally, has systemic benefits. So we will be watching that one and reporting on statnews.com. But now, Adam. Yes, Allison. Tell us. Tell us about the tale of Richard Graydon.

7:04You listeners might remember that Elaine and I were discussing this last week. The biotech executive, it turns out, that was living life under an alias as he had skipped bail, I believe, and was living on a yacht for the last 20 years. You found out a little bit more information about him. Yeah. So while I was on my sickbed last week, I know you guys mentioned it in the podcast. Yeah, sort of a crazy story. And Allison, as you had said, you know, kind of a big story here in New England, right? because Ronald Fisher was a former physician. He had been accused of rape back in 2005. And during his trial, he skipped out on the trial.

7:45He ended up being convicted in absentia, but was on the lam for 20 years and then was caught on July 16th. Authorities tracked him to a sailboat off the coast of New Jersey, as you mentioned. And so the interesting twist of the story is that the boat that he was caught on was registered under the name of Richard Graydon. And, you know, when I wrote the original story, you know, there was some uncertainty as to like how this all came about and whether, you know, was Richard Graydon a real person or was it an alias that that Fisher had concocted? And it turns out that indeed, this was the Richard Graydon alias and persona was something that Fisher concocted in part to escape justice and to live a life as a fugitive for the last 20 years.

8:36And so I've been doing some reporting on kind of like more like maybe the last 10 years or so. We have uncovered evidence that, you know, he was kind of leading this secret life as a scientist and as a biotech executive, biopharma executive. and a new story this week kind of with more details and like, you know, his work in biopharma was more extensive than we had previously known. Yeah, this was really fascinating to hear about. I mean, this has been a local kind of New England story. The fact that it extends so deeply into the biopharma world really caught people's attention. I mean, I got to tell you, I've spoken to multiple people working in the industry this week who are talking about this story and are questioning how this guy lived and operated in our industry for so long.

9:30And at multiple companies, Adam, you've talked to some folks. You found a recruiter who has interviewed this guy, Richard Gray and Ronald Fisher, multiple times over the last, what, five or ten years about different positions. Yeah. Yeah. Yeah. You know, one of the questions that you guys asked on the last podcast, and it's the question that everybody asks, is like, how did Ronald Fisher concoct his persona, this fake alias, this Richard Graydon character, and get these jobs? And the answer is really simply, it's kind of disappointing, simple answers that no one seemed to bother to check as to whether or not, you know, his credentials, including his academic degrees, you know, his academic training, you know, in the CV that he concocted under this Richard Grady Ellis, you know, he said he went on.

10:19He got a medical degree at Stanford, that he trained at Harvard, that he was a board-certified hematologist-oncologist, and he had this extensive career as a kind of a drug developer, working at some of the biggest names in pharma. And nobody seemed to bother to look to see whether any of this was true. And because of that, he was able to get these jobs. And like you said, Allison, I after the original story came out, I a health care recruiter reached out to me and said, you know, had read the story and said, you know, I I've talked to Richard Graydon. And the first time that this recruiter spoke to Graydon was back in 2020.

11:02There was a job available at Bristol-Myers Squibb to kind of help manage their phase three oncology trials. And this recruiter was helping Bristol try to find qualified candidates for that position. And Richard Graydon's CV, because he was a board certified oncologist or claimed to be. He claimed to be. You know, that sort of put it. He claimed to be that sort of put his CV at the kind of the top of the list. As a recruiter told me, it sort of put him on a pedestal. And he called. He called Richard Graydon and to talk to him about the job. Yeah, it was fascinating to hear a couple of different perspectives on his how he managed to kind of circumvent the hiring process at multiple companies or try to circumvent the hiring process.

11:54As we were saying, you know, he claimed to be a board certified oncologist. In fact, he was an anesthesiologist. Correct. But nobody, it seems, was checking his medical license because if they tried to check his medical license, it would have shown that there was no medical license under the name Richard Graydon. Right. Yeah. And so, you know, in the in the like, again, in the extended reporting that I did for this week, kind of looking deeper into what he was doing. You know, I found that he he'd gotten he'd actually published some research on a on a kidney disease drug. He worked for three years as a contractor with Daiichi Sankyo, the Japanese pharma company.

12:39Again, under one of their contractors for three years from 2016 to 2019. He actually some of the work he did actually ended up giving him credit as an author on an abstract on some data that was presented at both the the ASCO and hematology meetings in 2019. He spent a little bit of time working as a contractor for J &J. He you know, as we as we previously reported in our other story, in our first my first story, you know, he was the interim chief medical officer at a small biotech company called the TASA Therapeutics. And then, you know, probably the biggest surprise was when he was hired as the as the full time is the chief medical officer of a small biotech company called Emix Biopharma.

13:24And, you know, I think, as you guys noted, you know, a chief medical officer that is the top, basically the top medical officer of a company. It's usually a position that is highly vetted and people have to be well credentialed. And, you know, from, you know, from what I've been able to learn, Emix has not spoken to me, but what I learned, you know, they said they did a background check and he passed a background check. But that's really causing some head scratching because you would think that if you did any sort of minimal background checking on this guy, you, as you mentioned, Allison, you would have noticed that, you know, that his degrees in his CV were fake.

14:00Yeah. Or that his social security number didn't match. I am also fascinated. I'm going to start asking every executive that I do a Zoom with to take down their little AI generated background, because I'm curious, was he doing all this work on the yacht? I'm really stuck on these little details here. Has he just been working, living on this yacht the last two decades? I mean, what's interesting is there's so much we don't know about his life on the lam. Like I said, you know, he had been missing since 2005, so more than 20 years. And what I've uncovered is just a small slice, you know, in the last, you know, call it five, 10 years.

14:42He, you know, he may have been living on the boat. I did actually, it's not in my story, but I spoke to someone who actually sailed with him. What? Back in 2024. You didn't tell me this, Adam. Well, you know, it's not in my story. It may end up in another story. But yeah, this person met Graydon at the marina in New Jersey where the boat was and they sailed together. Didn't know anything about his personal life or his professional life. Just kind of knew him through a sailing community. But at the time, he wasn't living on the boat. And actually, it's funny, his CV lists an address, his home address at an address in lower Manhattan.

15:22And we went to check. And that address is actually a UPS store on a fairly grimy block in lower Manhattan. So there's just a lot we don't know. And so, hey, if anyone's out there who happened to run across Richard Graydon over the last 20 years, drop me a line. This is I'm hooked, pun intended. Should we turn back to kind of drug news and Capricor, the company that has been in front of the FDA this week in one of the few adcoms that we've seen recently trying to get approval for its drug for Duchenne muscular dystrophy. Adam, talk to us about this meeting that happened this week. An FDA advisory panel took place on Wednesday.

16:12Capricor Therapeutics is trying to get its drug. It's called Daramiacel approved as a treatment for Duchenne muscular dystrophy. You know, and what kind of sets this drug apart, this treatment apart from some of the others that have been out there is that it had been tested in older boys. As we all know, Duchenne is a progressive muscle wasting disease. And this one was a little bit noteworthy in that they had tested the drug in kind of teenagers and older boys and even into their 20s. at a time when most of those boys with Duchenne are already in a wheelchair and are already further along in the progression of their disease.

16:50And that was kind of notable here. This was always going to be a contentious review. The company had sort of a rocky past with the FDA. They had, like we had mentioned with Replimune earlier in the show, they had also submitted once for approval based on some earlier phase two data that was really quite mixed and unconvincing. And they they got rejected. And then they did a phase three study, which purported to show that it had staved off upper muscle upper. I'm sorry. It had staved off upper limb muscle function, you know, basically allowing the boys to continue to use their arms to eat and sort of be more independent, even though they were in a wheelchair.

17:32And also, probably more importantly, also kind of slow the progression of cardiomyopathy, which is kind of a heart failure condition that affects boys with Duchenne. And ultimately, a lot of boys die of complications related to heart failure as the muscles around the heart weaken. And the FDA, I mean, it was a pretty blistering critique of the FDA that they put out on this review, basically disagreeing with just about everything that the company had said about the drug. And, you know, whereas the company said that the drug had met these endpoints, the FDA said, no, the drug did not. And so that was kind of the centerpiece of the debate and discussion on Wednesday with this outcome.

18:20Ultimately, the panel voted on Wednesday 9 to 3 against recommending the approval of the drug. They said that the evidence was not substantial and should not support approval. So, I would say the likelihood that this drug, Dermisil, gets approved is probably very low. The FDA review continues. I think the FDA has up until about August 22nd to make a decision. But, you know, based on yesterday's proceedings, approval is unlikely. And a big a big part of like where the FDA disagreed with the company is because Capricorn made changes to its statistical plans as the study was ongoing. And the FDA went with results based on an earlier statistical plan, while Capricorn went with results according to, you know, their their later statistical plan.

19:14Is that right? Yeah, that was a big part of yesterday's or Wednesday's meeting. There was a lot of controversy about this study. And there was various statistical analysis plans that were put out to the way that the company conducted the analysis and the way they collected the data from patients. The FDA used basically sort of the original pre-specified stat plan that had been drawn up prior to all of the patients completing the study, which the FDA thought was the most robust way of doing it, most conservative way of doing it. The company had made at least, well, multiple changes, but had sort of submitted at least two other statistical plans, one of which the FDA never really looked at.

20:06And that was, you know, maybe unsurprisingly, that was the one that put the drug in the best light. You know, sort of the, it seemed what was going on here was that they were changing the stat plan to make the data look better. And so, there was a lot of discussion about that and about what, you know, what that meant and sort of the robustness of the data and the credibility of the data. And ultimately, the FDA did a very, very thorough job of kind of explaining why Capricorn's version of the stat plans was just not the way to go. And yeah, let's dig into this further, because wasn't Capricorn's argument that, or at least some supporters of Capricorn, the argument was that it was fine to make the change.

20:54They did it before the study was unblinded. So it didn't really affect the process of the clinical trial. It really just affected the interpretation of the data, right? Right. Yeah, I mean, there was a lot of back and forth. And then, Allison, I think it's probably fairly evident to folks that if a company sees the data and then makes changes to the stat plan, that is very much a definition of manipulation and post hoc jiggering around data. And that's a big no-no. You know, that's that's and the FDA actually never really accused the company of doing that here. You know, at best, what they said, that there was a there was a potential that the way that the way that the drug worked, you know, because of the sort of side effect profile that patients could have been like sort of functionally unblinded to whether they were receiving daromia cell or placebo just because daromia cell does.

21:50You know, when you get injected, it does cause side effects that placebo doesn't. So patients may have known. And that may have caused sort of, like I said, a sort of functional unblinding. But there was never an accusation that the company had sort of like looked at the data and then made the changes. But what they did do was they did they did create these new stat plans, you know, after after all the patients had completed treatment and after the data had been in with still blinded. So, you know, it was a little bit of a gray area there, but still to the FDA's eyes, you know, if you're really if you're really kind of taking the most conservative point of view about how you review data and sort of the best way to view data, that was still kind of a no-no.

22:30There was something interesting that I thought one of the FDA officials said during this meeting. And this, you know, comes even as a lot of patients, there were a lot of patients coming, giving, you know, emotional testimonies about why they think the drug should be approved. And then an FDA official then made the case that actually rejecting drugs and being a very rigorous regulator is good for patients, which, you know, I think is kind of obvious. But I thought it was, you know, interesting that they explained that explicitly, you know, to the patients that were there. Yeah, yeah. It's good you picked up on that, Elaine, because it was really interesting.

23:08You know, I think the FDA is very sensitive to the criticism that they've received over the last year or so that, you know, what they have been doing is detrimental to kind of rare disease drug development and the rare disease patients out there. That they're, you know, that they're talking about wanting to accelerate approvals of drugs for rare diseases, but at the same time, they seem to be rejecting them. And there were several moments during the advisory panel where the FDA officials really stepped out to say, look, we hear you, rare disease community, patients with Duchenne. You know, we understand that we understand the need here.

23:48We understand the suffering that you're going through and why why these why new treatments are needed. And, you know, in the FDA as an agency wants to wants to approve new treatments. But at the same time, I think, as you noted, you know, they did say that, you know, using high sort of high standards for drug approvals and, you know, the need to sort of to demonstrate that these drugs have a substantial evidence of efficacy. Really, those rules exist to actually protect patients. Right. Because if you approve a product that doesn't work, you're actually exposing patients to risk. And so I think that's kind of a point that they hammered home a few times.

24:30And particularly, as you said, Elaine, after there was 90 minutes of public testimony from patients and patient advocates. And some of these stories are really, they're heart-wrenching stories. You hear people, we heard directly from patients with Duchenne, both who have used this drug and who haven't. And, you know, and I think that that was something that the point they made. And, you know, when Replimune, you know, you're covering that advisory panel today. And I'm sure that there will be patients with melanoma who are going to be testifying today at the at the Replimune hearing. And you're going to sort of hear that those those same messages.

25:12I do have to. OK, wait, call like a little bit of of BS in this this Capricor example, simply because if we look at. obviously, yes, on paper, the agency's job is to protect patients and safeguard them against therapies that don't work or could harm them. But if we look at Duchenne muscular dystrophy, this same condition, slightly different patient population, we have seen the agency approve therapies in Sarepta's therapies that don't have proven efficacy. We still haven't seen the data right on Exondis 51 that verifies that it works. Why is this patient population, the slightly older boys who are arguably more ill, the sicker, why are they being treated different?

26:02Well, I think that's a fair question because I'm sure, you know, like the patient population feels like there's just inconsistent standards being given out by the FDA. And I think it does go back to who specifically were the leadership in charge when these various decisions were made. The Sirepta drugs were approved under a different leadership. But this kind of relates to one last question I had, which is a lot of the restrictions on approving drugs that occurred under Vanai Prasad Capricorn's initial rejection that occurred under Vinay Prasad, kind of people were quick to attribute it to Prasad and say, you know, this is how he does things.

26:51He is very skeptical. And he, you know, is a very, very, like restrictive regulator. But we're seeing that he's left now for a while and FDA staff clearly still are skeptical of the Capricorn drug. So I think, you know, is it fair to have attributed the decisions that occurred under Prasad to him specifically, when it seems like, at least in some cases, there is consistency in how FDA staff are looking at these drugs even after Prasad has left? I think we always, it's a good reminder that we have to look at each drug on its own in some respect, and that every drug has its own data under circumstances, and every drug will have its own benefit and risk, and that's ultimately what a decision should be based on.

27:39I think, you know, we've done a lot of reporting. Obviously, we've done a lot of reporting on Van Iversad while he was there. And it overlapped with the reporting both on Replimune and on Capricorn. You know, as we previously reported, I think in both of those cases, there was definitely a mixed view within the agency about whether these drugs were approvable or not. And that, you know, that's maybe maybe the fault is, you know, that's not unusual. You know, it's maybe it's more rare than we think when there is a clear consensus on some of these drugs. So, you know, I think that there's a lot, you know, I think everyone will be sort of quick to kind of look at these through the lens of, you know, was Vinay right?

28:26Was Vinay wrong? wrong. I don't think anybody who sort of really kind of looked at it fairly and sort of even handedly will say, you know, that there's absolutes here, right? That, you know, he was rejecting all drugs or he should have been approving all drugs. But these are two cases in particular where there was just, there were always, you know, as we've reported, you know, going way back, that there were issues with these drugs. There was issues with the data. I think we've learned more, you You know, the issues with that replamines drug, I think we've known for longer. Like, you know, I had reported back that, you know, this really wasn't, you know, the initial rejection really wasn't about Vinay Prasad.

29:06It was more about Richard Pastor, you know, at the time who was head of the cancer division within the FDA who had objections to the drug. And, you know, the stuff we learned with Capricor, I think, you know, was, you know, again, I think, you know, honestly, you know, frankly, sort of disappointing. Right. I mean, you know, they they changed the stat plan. And if what we know today about the statistics, some of which, again, I mentioned the sort of heart failure stuff, the company had originally claimed that that was stat sig on the primary endpoint. Well, we learned yesterday, because they had also published the data in The Lancet yesterday, that actually it wasn't.

29:47Even under their new stat plan, it was not stat sig. Right. And that would have changed the whole tenor of the discussion, you know, back late last year if had we known that and we didn't know that. Playing devil's advocate, do you think it's possible that by knowing the reputation of Anai Prasad, that perhaps biotechs took advantage of that in trying to put the blame on the FDA for restricting drugs when he was the one in leadership there? That's a good question. It's possible. And it's a good question. It's possible. Well, you know, we I think from the very beginning with Vinay Prasad is that I think everyone recognized that he you know, one thing that he did incredibly well was, you know, interpreting clinical trial data and being able to sort of suss out deficiencies, shortcomings in clinical trial design and analyses.

30:39But I also think you have to recognize that his tenure at the FDA was more about was was was about more than just the way drugs are reviewed. Right. I mean, he needed he was managing a very, very large part of the FDA. And there were issues with the way he ran the division. And there were problems that he had that, you know, our colleague Lizzie Lawrence had reported over time that, you know, went beyond just, you know, whether he liked a drug or didn't like. And that played a role in in what happened there. It played a role in the large number of people who left the agency and ultimately played a role in in why he left.

31:21So, you know, it's not just about drug reviews. Yeah, I think that's a good point. And as we heard last week in our interview with Matt Wilsey, there was a really sharp change in tenor in how he approached kind of the drug review process. And even before review, how he approached communication with biotechs. I mean, Matt talks about in the interview that we did last week, basically all communication with the agency drying up under Vinay Prasad. I think it was like in retrospect, it's very easy to look at the inconsistencies that emerge in different areas, different eras of leadership at the FDA and call foul.

32:07I don't know. Time will tell where we land on Vinay Prasad.

32:20all right read out loud listeners we have a bit of sad news on the episode today our dear producer hyacinth is moving on to a new opportunity and we are going to miss her terribly hyacinth let's hear you on the pod come join in tell us where you're going yeah i am uh going to the conversation. It's a nonprofit news outlet that centers academic voices. So the academics and scholars write the articles and it's edited by journalists. So I'll be their new global health video producer. So I'll be doing social video, hopefully long form like explainer videos at some point. So yeah. Well, we are so happy for you, Hyacinth, but we are going to miss you so much.

33:03it's not going to be the same. I'm going to miss you guys. And Hyacinth, I have to say you and I you are the OG producer of the Read Out Loud. You were there at the very beginning when Damien Garda and Rebecca Robbins and myself thought that we knew what we were doing with a podcast back in I had to look up the date, Hyacinth. March 2018. 18. Okay, gosh, it's been a while. And we were like, I remember we were huddled in the conference room. We had these like rinky dink mics attached to your, yeah, yeah, yeah. We didn't have the fancy Yeti mics that we now have recording over Zoom. We had nothing fancy and we had no idea what the hell we were doing.

33:53But we were in this great adventure with you. And so, you know, I feel like a foundational part of this podcast is leaving. And so I am sad for that. You know, you were around during all the COVID episodes. And, you know, so I have to say just it's been an incredible pleasure working with you and helping us through this amazing time that we've had. And I did tell Damien and Meg Terrell, another one of our former podcast co-hosts that you were leaving, and they both expressed their love for you and told. And they wanted me to tell you how how appreciative they were of all the work that you did on the podcast.

34:37Oh, that's so nice. I'm going to miss you guys. You don't have to leave. I'm just saying. I mean, I think a piece of me is like stuck here. Every time you publish a podcast, I'm just going to like put like a little audio, like a little audio note in there just to sneak it in.

35:05and that does it for another episode of the read out loud thank you to hyacinth empanado for producing this week's episode her last episode with us our senior producer is alissa ambrose our executive producer is rick burke and our theme music is by brian joel and we'd love to hear from you tell us what you like about this episode what you didn't like and hey have you ever met Richard Graden, send me a line. You can do all that by sending us an email at readoutloud at statnews.com. And if you like what we do, leave a review or rating on Apple Podcasts or whichever platform you use to get your podcasts.

35:40This is where I normally say see you next week, but we are shutting down the podcast for the month of August. We're going to have a bit of a European August here at the Read Out Loud, take a little hiatus, and we will be back in September. Until then, enjoy the rest of your summer. Bye, folks. Bye.