406: New hope in treating Huntington's disease and a report card on RFK Jr.'s promises

[music] Welcome to this week's episode of The Read Out Loud, a weekly biotech podcast from STAT. I'm Allison D'Angeloos. I'm Adam Forrestine. And I'm Elaine Chun. It's Thursday, June 18th, and on this week's episode, we're discussing a new hope for Huntington's Disease Patients. Yeah, that's right. Unicure has gotten the green light to submit its gene therapy for approval, patient advocate, Lauren Holder returns to the podcast to discuss. Our colleague, Esa Cueto, is also joining to dissect how R.K. Junior is fearing on his promise to remake health in America. But first, a word from our sponsor. [music] I'm Mika Cueto-Durink, SPP of Oncology at Gilead Sciences. At Gilead Inkite, our work in oncology starts with a simple question, how do we make progress truly meaningful for patients? As 2020, our therapy has been used to treat more than 75,000 people worldwide with metacetic, triple negative, and HR positive, Hurtunegative breast cancer. We bring that same patient-first mindset to other areas of high-end met need, including CAR-T-cell therapy for people with difficulty to treat blood cancers. Today, over 34,000 patients around the world have been treated with CAR-T-cell therapies from our portfolio. Across oncology, this perspective guides how we design clinical trials and pursue innovations so patients can access potential advances throughout their treatment journey. Learn more at Gilead.com Listeners to this podcast I've heard us talk quite a bit over the past year about the biotech company Unicure and its efforts to develop a gene therapy for Huntington's disease, a devastating neurodegenerative disease. Data from a small study showed its treatments slow the progression of Huntington's by 75% after three years. Current medicines on the market don't slow disease progression. They only treat symptoms. Efforts to bring Unicure's potentially disease-modifying treatment to patients has been delayed, though. The FDA, under former commissioner Marty McCarrie and Vanipersod, said Unicure study data were insufficient to support approval. Now, McCarrie and Prasod are no longer at the FDA. And on Wednesday, we learned about a new and important development in the story. Unicure and the FDA met again recently, and this time, the two sides hammered out an agreement that clears a path for Unicure to submit its gene therapy for US approval. The company said that it will submit that application in the third quarter of this year. Joining us to discuss this new development and what it means for the Huntington's community is Lauren Holder. Lauren is a Huntington disease advocate who is living herself with the early stages of the disease. She's also the producer and host of the Hope4HD podcast. Lauren, welcome back to our podcast. Thanks so much for having me back. Lauren, before we get into the news, we wanted to check in to see how you're doing. When we last spoke to you on the podcast in January, you said you were feeling some of the cognitive and behavioral symptoms of Huntington's. Yes, and that's still accurate as far as the neuro-cognitive disorder related to HD. But I do have to say I come back to you guys more hopeful and happy today than I was when we originally talked. Yeah, tell us a little bit more about that. What was your reaction when you heard the update from Unicure this week that it has a clearer path to an FDA submission? I honestly cried. So I was woken up to my phone blowing up and everybody trying to tell me what was going on. And yeah, I mean, I started crying because of the relief I felt that we finally have people at the FDA who are listening that we were heard. And that Unicure is going to be able to move forward as originally planned, the original guidance that was provided and that we are actually one step closer to this being a reality for patients. Lauren, I think I was one of those people who sent you an early morning text about this because I saw the news this morning. I was up in early writing about it and wanted to get your reaction to it. What else did you hear? And obviously I'm sure you were speaking to a lot of folks in the in the Huntington's community and kind of what was the overall reaction to the news? Well, I was so it was funny because I was getting so many different messages at them. I was getting from from you. I was getting from people on X who have been following this religiously as well as the community and the community themselves very much was so much excitement and the fact that we crossed this hurdle and we were able to solve this barrier because if I'm being honest, a lot of this was because of advocacy and patient advocacy in the community not giving up. And so a lot of them were feeling relief and excitement, cautiously optimistic, right? Because again, we've heard this before but I think it's a different environment because of the fact that we went through something so terrible and the new people at the FDA are actually hearing us and trying to move forward in a different way. So lots of excitement, cautiously optimistic and lots of congratulations from outside of the community which has been really wonderful to receive that from the people who have been helping online and really helping us push things and get things communicated. So I'm so grateful to everyone who has been part of this and helping us fight. Of course there is still a lot of uncertainty, right? Because the FDA has agreed to review the drug. Obviously, we still don't have actual approval yet. Yep, so this does not mean that it's approved right now but what it does mean is that the FDA is willing to accept an application from UNICARRE for accelerated approval with confirmatory trial to review that application and that they are going to work with UNICARRE. And this is what's more exciting is just the fact that they're going to work with UNICARRE to make sure that they can submit that application and move forward which is great. And I mean the other big part of it is that they're no longer requiring that sham procedure which would be a death sentence to our community. What do you think led to this reversal, this kind of change in tone at the agency, at the FDA? You mentioned that obviously there's been a leadership change as all this has happened. Did the Hientingen community actually meet with the acting commissioner? What I, so I think it's a number of things. I think that it's a change in the people at the FDA, the administration. And I also think that we were heard by the necessary people about what was going on with our community and that our patient advocates have done a really wonderful job in getting to the right people. That includes, you know, I personally have talked with Senator Ron Johnson's office, provided them information. Katie Jackson has truly been the powerhouse through all of this and herself has met with the necessary people and has gone to DC recently to advocate on our behalf. So I think that it's all of us working together and really trying to just get in front of the necessary people to voice what's going on with our community in particular. Have you sensed a more open line of communication? Absolutely. I mean, the FDA today, then it was, let's say, months ago, you know, back when McCarrion presided over there. Absolutely, absolutely. I think, you know, and even Katie Jackson, the CEO of Help Grach, he said to me when she was in DC that things seemed more relaxed and happy and she could tell a difference while she was there. And that's huge. But I also, you know, have been invited. I was invited recently to participate in webinar series and one of the people who invited me was Michelle Campbell of the FDA and then Torina of Critical Path Institute. And that type of communication, not that, you know, they were involved with what was going on at SEBUR, but they were not able to really communicate with us and things had kind of stopped as far as I can. communication goes that has come back and so I've you know I've been receiving those invitations for participating in the webinar series and other things so yes I would say it's definitely improved. Going back to when there was that roadblock at the FDA under Makari and Prasad during that time the disagreements were pretty intense in March a senior FDA official speaking anonymously had told reporters on an FDA sanctioned conference call that unicure was pushing quote distorted and manipulated clinical data for a quote failed therapy. What was your reaction when you heard those comments? anger. I was very angry over the fact that somebody could go to media and go publicly and say that it was a failed therapy when there was not indication of it being a failed therapy that was such a lie. In fact the data shows otherwise but this is not a completed trial and for a government official to anonymous or not to go and say that publicly is not only hurting the trial and hurting the pharmaceutical company they're hurting the community because they're lying to the community and there were so many people in the community who actually said well are they you know is this person right? Is this why you know it's not moving forward even though our H.C. experts have backed this and everybody else has backed this and it causes confusion it causes a devastating and negative effect with rare disease communities when you go public like that on something that that one is not done and two you know it's not true it's a lie and the data shows otherwise so I was very angry because we as patient advocates really had to go back and try to fix that mess and and I can't tell you how grateful I am to not only Adam who in his wonderful reporting of all of that but also the other reporters out there who who actually reported honestly about what was going on but you know it's sad that we as the H.D. community the Huntington's community have been publicly disparaged I have not heard that happen to any other rare disease community during this time but we have publicly been attacked and disparaged and our specific treatment light about and disparaged and it's just sad that that's what happened with government officials. You're too kind Lauren I appreciate that but I but I do and you may not have direct knowledge of this and it may just be your opinion but do you tie the the leadership the recent leadership change at the FDA with the news this week do you think that those are directly related? I do I do think it has a lot to do with it the leadership change was obviously a huge problem and the things that were that were changing based off of the previous people in office and I also think it was acknowledgement from higher administration and the realization of what was going on because if we also think about what else has been going on you know with a with a war and everything else you know it's hard to realize everything that is happening in all of the in all of the different government entities and bodies and so I think it's also just a realization of what those previous FDA officials were doing. Yeah Lauren I want to touch on one of the other controversies around the Unicure Clinical Plan and data package that was discussed you know with previous FDA officials you know old FDA leaders meaning McCarrion Prasad wanted the company to evaluate the gene therapy in comparison to a sham surgical procedure in which you know patients who were receiving the placebo would actually have to undergo a surgery. On Wednesday Unicure indicated that a sham surgery control might no longer be on the table it might no longer be necessary and I mean many of the patients when they had heard that original guidance thought that that was unethical to make patients undergo a sham surgery what's your reaction to what it seems like is the FDA maybe easing up on its placebo control you know requirements for a confirmatory study. So that's huge because because again it goes back to the fact that this is what we have been saying in that that sham surgery would be a death sentence meaning that you know Unicure already tried to do a sham arm and one year and it was they spoke with the FDA and I believe Peter Marx was there at the time and specifically like told them that it was not ethical to continue after that one year because people participants not all of them but some were progressing to a point where they were no longer eligible for the treatment and that was part of it and the other part of the argument is that you know when you have somebody who has a sham procedure in a gene therapy trial okay this is a one and done and we were told at the beginning that if you participate in this trial you can no longer participate in future research. So if you're putting somebody through a sham surgery where they're not receiving drug now they can't even receive the actual treatment from Unicure because they their their brain volume is no longer at the point or they've progressed too far in the disease that they can't receive the treatment you have now caused a death sentence to somebody because they can't even participate in other research to be able to look at other treatments and so that was their argument and the FDA at that time was willing to accept natural history when McCarrie and Prasad came in Prasad made it very clear that he felt that that they're needed to be a placebo sham arm because he does not agree that natural history is sufficient enough even though a precedent has already been set in this argument has already been discussed in a decision made and so it made it very difficult because what you're saying is you expect for people with HD to again be part of this of this sham arm and and be blinded and potentially not be able to receive the actual Unicure treatment if they progress too far within that time which they will if the requirement is for the full you know full phase three which is years and then they also can't participate in future research so yeah I mean it's a death sentence not one of us would be willing not one of us in the community would be willing to do that we even talked as a community about going overseas if it meant being able to get this treatment not have to do sham surgery so this part is huge this means that again this is on the table for the U.S. we're not having to look at potentially going overseas for treatment through Unicure and that the current FDA administration heard what we were saying about about that sham surgery and that sham arm and I can't tell you how much that means to be heard on that because that was such a huge that was such a huge thing to for a facade to just act as if none of that mattered and he really didn't care and it showed he did not understand Huntington's or the actual trial itself you know learn one of the criticisms of this situation has been you know just the the the small number of patients treated with the Unicure gene therapy to date at you know the relatively small amount of data that that they will be reviewing to base so this accelerated approval on is it still important to collect additional data I mean you know we talked you talked very eloquently here about you know the how doing having a sham surgery would be unethical but do you still want Unicure to to conduct additional data trials with this treatment to collect more data to kind of get a better sense of what it's you know what it might be doing for patients absolutely absolutely I think the idea of this confirmatory trial with accelerated approval is great because then they are required to get that data and we will know and if it doesn't work then they can pull it but for the of us who don't have the time to wait for this and need to try whatever is available to us. You know it's like a brain cancer. We wouldn't do that to a patient with brain cancer. We wouldn't refuse the option to them. And so we should have the option. We should have the choice to make ourselves as the patients. And so I really really love that they are requiring this confirmatory trial alongside the accelerated approval. So that data is gotten you know is received because I yes I think it's very important for them to still do it. Well Lauren thank you so much for coming back on and sharing your thoughts and experiences on this. Thanks for having me. I really appreciate it. A pledge to make America healthy again earned Robert F. Kennedy Jr. his job as the Secretary of the Department of Health and Human Services and he entered the role with a long to do list and a goal of delivering measurable improvements within two years. More than a year into the role how has system faired? Issa Quedo Stats chronic disease reporter has been closely tracking Kennedy and the Mahab movement sections. So we wanted to bring her on to examine where Kennedy's plans have turned into action and where they fall in short. Issa welcome to the podcast. Issa we wanted to start off with one of the more recent focuses of Kennedy which is psychiatric medications. Some prominent voices in the Mahab movement believe mental health drugs do more harm than good and Kennedy himself has called them addictive. Last month HHS began encouraging physicians to wean patients off of medications. Tell us more about that. Yeah, so this has long been a discussion in Mahab circles. There are people who I've met who are at you know basically every big HHS event and have personal experiences of trying to get off of anti depressants and finding it very difficult and they are having conversations with HHS leadership. They're meeting with FDA officials. This has you know become part of the agenda and now is turning into action. So as you mentioned HHS sent a dear colleague letter out in May and they have plans to issue a report on the prescription practices for psychiatric medications and then start hosting some webinars for doctors to you know learn how to get patients off of these drugs and then they also want to develop some clinical guidelines for you know the quote unquote proper use of psychiatric medications. So there's a lot happening in this space. Kennedy has also had a long standing very stringent desire to overhaul childhood vaccination policy. Where has he succeeded and where has he run into problems? Yeah this is probably the area that's seen the most action. It's obviously a big focus of his and Kennedy was successful in appointing advisors who overhauled the childhood vaccine schedule and reduce the number of shots that would be recommended for American kids to bring the US in line with what some other nations recommend. However those changes have been blocked by a lawsuit and then Trump has stepped into the fray and issued an executive order this month trying to re up the changes to the vaccine schedule. So it's still to be seen how that is going to play out and it's also worth mentioning that healthcare providers and hospitals are saying we're gonna stick to the old schedule we're not gonna restrict what people can get. That being said there's been rollbacks to programs that cover MM are vaccines for low-income children for example. There've been talks about splitting up the MMR vaccine into separate shots which could also reduce uptake and we're already seeing declines in vaccine uptake in children which is heavily influenced by rhetoric from the top of the federal government. Especially as we approach them in terms of it does seem like the Trump administration is trying to perhaps reign and Kennedy more on the vaccine stuff right? That's what the reports are and we've definitely seen that there's been less public commentary about vaccines but I really would be surprised if this falls off his agenda. I mean this is how Kennedy not made a name for himself because he is a Kennedy but this is how he grew his following and this is what he basically has run on for years and so he needs to stay loyal and deliver for that core base. You know on a related topic there's been reporting that you know particularly as we get into the midterms and after the midterms that maybe Kennedy is not it's not as in it's not spending as much time on the day-to-day operations of HHS that other other officials there have kind of taken more day-to-day control in that he's kind of and as a New York Times reported recently that there he's not necessarily interested in kind of being kind of a very active hands-on HHS secretary he has this issue that he wants to spend time on including vaccines. R.K. has responded kind of you know responded pretty angrily to some of that reporting and one of the issues that came up is R.F.K.'s calendar and like how how does he spend his day and days and weeks as HHS secretary what have you guys been able to do Gleene from R.F.K.'s calendar particularly whether you can even have access to it. Well yeah that's the thing so in an angry post on X in response to the Times reporting he said you know all you have to do is look at my public calendar to see what I'm up to and to see that I'm constantly working but there is no such public calendar and we know that because several of us at STAT have been trying to get Kennedy's calendar for you know a year and a half at this point we've we've asked we have filed FOIA requests freedom of information requests trying to get that information and we have gotten absolutely nothing and so it's very hard to know what his day-to-day life entails you know beyond what we can sort of observe or videos that are posted of him at the gym in the morning or things like that. Yeah ESA if we step back and we look at this first year and change about his of Kennedy's leadership what how is it played out with regards to what we kind of expected or you might have expected at the beginning some of these policy initiatives are very well known like vaccine policy it sounds like there's also been some less you know some things that weren't really his talking points that he's it really been active on. Yeah it's interesting I mean I didn't know what to expect when he became health secretary last year other than that he would be very dogged because he you know in in listening to and reading what he's said for years he's extremely consistent with what he says with you know the research that he cites with who his confidence are so that hasn't really changed very much but it is notable that as part of like the presidential maha commission there's this long set of goals that were outlined there and those you know brought in the reach so those involve like NIH research projects into various issues including chronic disease they also extend to things like sunscreen which like that's one of the things that has happened in the past couple of months is that the FDA approved the first new sunscreen ingredient in the US in decades and so that's like you know one of the things that is marked as a accomplish in our tracker but of the 80 promises that we've been keeping track of about two dozen of those have been kept or are you know in progress and the rest of them they're you know not moving or they've been completely broken or their status is just unclear so there's still a lot of work left for him I think there's been a lot of activity obviously I mean the coverage has been sort of unrelenting since he became health secretary but there's still much to do another one of his promises has been to ban direct to consumer pharmaceutical advertising which is one of the ways that drug companies in the US are able to drive sales it's not really something that we see anywhere else in the world it's banned in other countries but we still see drug ads all the time why is that well yeah so Kennedy is well known for saying that the US is like one of two countries in the world that allows direct to consumer pharmaceutical advertising and how that is like a reflection of perverse incentives and corporate influence etc and he has repeatedly talked over the years about the need to ban these sorts of ads and he also has connected it to like his own political ambitions saying that the mainstream media TV networks don't treat him and his people fairly because they're backed by farm advertising and for transparency stat has also been accused of something similar And he is not really acted on that though. In September, the FDA said it would crack down on quote unquote deceptive ads and inappropriate promotions by influencers on social media and telehealth companies. And we're seeing a little bit of movement on that front. But it seems like they sort of clammed up on the issue of banning it. Kennedy was asked about this and said that his agency is looking into the legality of it. But they stopped making these flashy comments about DTC advertising and redirected the focus elsewhere. So I think what we see, particularly in this kind of politically divided world that we live in that policies get enacted, another administration comes in, and then those policies are reversed. New policies are put in. But when it comes to food and nutrition, that's something that RFK seems to have spent a lot of time on, do you think that that's some of the changes that he made there? Do you think that those are more durable? Like do you think that those would perhaps continue? And would be me one of the legacies of his time at HHS? Yeah, I think so. I mean, consistently when I talk to people, this is the area that they're most excited by and happiest about, even if they disagree on everything else like you're saying. And some of the changes are more durable. So for example, the update to the dietary guidelines, those influence federal nutrition policy and school meals. And so if the dietary guidelines say, look, you need to reduce ultra-process foods and added sugars and focus more on protein and whole foods. And that actually is implemented at the school level. That could be a major change that would definitely have lasting consequences. The devil is in the details, as always. And so the exact implementation in schools is still to be seen. The guidance is still pending. But those sorts of things are broadly popular. The ultra-processed food conversation has also really gone mainstream. I mean, Kennedy is definitely not the first person to talk about junk food being bad for you. And some people criticize him as relabeling old ideas and making them his own. But everybody is talking about this. Everybody is looking to products that have artificial dies and trying to see how companies are trying to reformulate to adapt to changing consumer tastes. And so this is definitely not a momentary trend. I think this is something that has legs. And I think it's well in line with broader health movements of people using wearable devices and cutting back on alcohol use and all of these other things that reflect American health consciousness. I want to touch on the strife that's been happening between the scientific community and HHS over this last year in change. Kennedy really came in and kind of wanted to disrupt or change a lot of the institutional ways that these departments operated. But I wonder are there areas where actually researchers would welcome Kennedy and his team making changes? I think about things like clinical trials. That's a big topic of conversation in the drug industry and changing them to be more effective. Are there actually any areas where people would welcome Kennedy's changes? I think so. I mean, I think there's kernels at the center of some of his promises and priorities that are shared. And so one example is the idea that biases and corporate interests should not influence science and we should take pains to try and protect the scientific endeavor from that sort of influence. But it's hard because then you see complex of interest and biases affecting the federal health agencies takes on things and policies. And you're like, well, wait a minute. How is that different from what you were alleging was happening before? Are there areas where HHS is investing resources to study things that maybe have been underinvested in in the past? So one of the new things is our page is launching this $144 million project focused on microplastics. And so those are welcome infusions of cash and welcome interest. But I think broadly speaking, the scientific community is hesitant to root for that because they're always sort of waiting for the other shoe to drop and wondering how their work will be affected by this HHS Secretary's agenda and views. So it's sort of fraught, I would say, the relationship between American scientists and Kennedy. Esa, thank you so much for coming on. And we hope to have you back on soon to talk about what he has or hasn't achieved. Thanks, y'all. [MUSIC PLAYING] That does it for another episode of The Read Out Loud. Thank you to Theresa Gaffney for producing this week's episode. Our senior producer is Elissa Ambrose. Our executive producer is Rick Burke. And our theme music is by Brian Joel. We'd love to hear from you. Tell us what you like about this week's episode, what you didn't like, and whether you're noticing a change in the FDA. You can do all that by sending us an email and readout loud at statnews.com. And if you'd like what we do, leave a review or rating on Apple podcasts or whichever platform you use to get your podcasts. See you next week. [MUSIC PLAYING]