Last summer, something monumental happened. One of Uncuffed's founding producers, Greg Eskridge, came home after more than 30 years in prison. In this episode we’ll bring you back to that emotional day last summer when he walked out of the San Quentin gates, free at last. Our work in prisons is supported by the California Arts Council, the California Department of Corrections and Rehabilitation, independent foundations, and donations from listeners like you. Learn more, sign up for Uncuffed news, and support the program at www.weareuncuffed.org Follow us @WeAreUncuffed on Instagram and Facebook Transcripts are available within a week of the episode coming out at www.kalw.org/podcast/uncuffed…
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S5 - E26.5 - Looking Back at #TLM2024 - Promoting Healthy Livers and Looking Ahead to 2025
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In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews two sessions promoting healthy livers and asks panelists what they anticipate for #TLM2025.
This last conversation starts with Jeff describing the session that moved him most and praising a panel that Mike co-chaired on Lifestyle Management of MASLD and MASH. Jeff spoke on this panel, and he describes the breadth and quality of speakers and topics. While Jeff spoke about social determinants of health, others discussed commercial, regulatory and lifestyle determinants, all intermixed with practical advice on managing patients' lifestyle issues. Finally, he comments on a presentation from Meena Bansal discussing several concurrent posters in the meeting that aligned with the discussion in the session.
After Jeff shares the content of the meeting, he comments on the large number of providers and industry executives who attended this patient-centered session. Roger notes a similar distribution of attendees at the Health Livers, Healthy Lives session on building momentum for prevention.
In wrapping up the session, Roger does not share another presentation but notes how many modes of action have produced successful Phase 2/3 trial results. He notes that we may have 4-5 different modes of action available five years from now.
In the rest of the session, panelists describe what they believe will be different and exciting at #TLM2025. Answers vary, but most focus on advances in drug development and/or NITs.
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In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews two sessions promoting healthy livers and asks panelists what they anticipate for #TLM2025.
This last conversation starts with Jeff describing the session that moved him most and praising a panel that Mike co-chaired on Lifestyle Management of MASLD and MASH. Jeff spoke on this panel, and he describes the breadth and quality of speakers and topics. While Jeff spoke about social determinants of health, others discussed commercial, regulatory and lifestyle determinants, all intermixed with practical advice on managing patients' lifestyle issues. Finally, he comments on a presentation from Meena Bansal discussing several concurrent posters in the meeting that aligned with the discussion in the session.
After Jeff shares the content of the meeting, he comments on the large number of providers and industry executives who attended this patient-centered session. Roger notes a similar distribution of attendees at the Health Livers, Healthy Lives session on building momentum for prevention.
In wrapping up the session, Roger does not share another presentation but notes how many modes of action have produced successful Phase 2/3 trial results. He notes that we may have 4-5 different modes of action available five years from now.
In the rest of the session, panelists describe what they believe will be different and exciting at #TLM2025. Answers vary, but most focus on advances in drug development and/or NITs.
1026 episode
Semua episode
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1 S5 - E26.5 - Looking Back at #TLM2024 - Promoting Healthy Livers and Looking Ahead to 2025 15:18
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Putar Nanti Putar Nanti Daftar Suka MenyukaiIn this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews two sessions promoting healthy livers and asks panelists what they anticipate for #TLM2025. This last conversation starts with Jeff describing the session that moved him most and praising a panel that Mike co-chaired on Lifestyle Management of MASLD and MASH . Jeff spoke on this panel, and he describes the breadth and quality of speakers and topics. While Jeff spoke about social determinants of health, others discussed commercial, regulatory and lifestyle determinants, all intermixed with practical advice on managing patients' lifestyle issues. Finally, he comments on a presentation from Meena Bansal discussing several concurrent posters in the meeting that aligned with the discussion in the session. After Jeff shares the content of the meeting, he comments on the large number of providers and industry executives who attended this patient-centered session. Roger notes a similar distribution of attendees at the Health Livers, Healthy Lives session on building momentum for prevention. In wrapping up the session, Roger does not share another presentation but notes how many modes of action have produced successful Phase 2/3 trial results. He notes that we may have 4-5 different modes of action available five years from now. In the rest of the session, panelists describe what they believe will be different and exciting at #TLM2025. Answers vary, but most focus on advances in drug development and/or NITs.…
1 S5 - E26.4 - Looking Back at #TLM2024 - Patient Advocacy and Patient-Centric Trials 11:44
11:44 Putar Nanti Putar Nanti Daftar Suka Menyukai11:44
Putar Nanti Putar Nanti Daftar Suka MenyukaiIn this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation considers the role of patient advocacy in replacing biopsy in clinical trials with NITs and reviews a session on the foundational principles for patien-centric clinical trials. This conversation picks up at the end of Michelle's discussion of the FDA Corner session. Jeff starts by identifying this specific issue - replacing biopsy in clinical trials with NITs - as a place topic on which he believes patients must play a pivotal role in this discussion. He notes that patient advocacy has been involved already but anticipates this role will grow as the discussion progresses. After Michelle agrees how vital this issue is for patients and notes that manufacturers are "taking on this increased workload" for that reason, Jeff shares what he considers the key issue: FDA is not only a scientific agency but also a political one, and patients can serve as the "tip of the spear" toward political ends here. Mike describes a poster he presented (and was lead co-author), titled Patient Voice in MASH Initiatives: Foundational Principles for the Conduct of Patient-Centric MASH Research . He lists the groups participating in this broad effort and describes the goal as "reimagin[ing] clinical trials for MASH and how they're designed and delivered... focusing on what matters the most for patients." The outcomes were a set of patient-centric principles: Transparency in explaining trial-related issues. Mike gave the example of placebos, how they are used, and what happens to a patient in the placebo cohort at the end of the trial. "Whole person focus," including not only the medical issues but also emotional and practical issues that can emerge throughout the trial as patients' needs and life situations change. "Patients as partners," treating them as collaborators instead of subjects. Family and caregiver awareness, noting how deeply involved family members are through the trial process. Responsiveness to patient needs through surveys and checkpoints throughout the process. Mike closed his comments by stating that all these points "put the patient at the center of the process," which meant considering not only diversity and inclusiveness in the trial population but also knowing and acting on what diversity will be in the context of these five principles. Speaking from their perspectives as researchers, Michelle and Jörn were both highly supportive of the principles (Michelle called them "fantastic.") Jörn noted that the entire trial process starts with patient-centricity since the research is inherently designed to benefit patients.…
1 S5 - E26.2 - Looking Back at #TLM2024 - Patient Genotyping and MASH Clusters 14:27
14:27 Putar Nanti Putar Nanti Daftar Suka Menyukai14:27
Putar Nanti Putar Nanti Daftar Suka MenyukaiIn this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation considers how the anticipated approval of a second MASH drug without biopsy might affect clinical trials and discusses two recent publications on patient genotyping and patient clusters. The conversation starts with Roger asking the group whether the presence of two approved MASH medications that do not require biopsy will make recruiting clinical trials that require them more challenging. The group doubts this will not add a significant new challenge to already-challenging trial recruitment. Naim comments that while this is a concern, it is already factored into trial schedules and that, given the number of patients available for trial, this should be highly manageable. Michelle discusses the importance of risk stratification in overall trial enrollment and this issue. Jeff and Mike agree that while this is a concern, it is part of a broader concern about the use of biopsy and should not in itself be a primary focus in terms of trial design at this point in time. Naim introduces two other topics he considers worthy of consideration: the impact of synergy between resmetirom and GLP-1 agonists and the importance of different genetic polymorphisms in predicting the impact of drugs on specific patients. On synergy, he comments that MAESTRO-NASH data suggests that the presence of a GLP-1 does not affect the impact of resmetirom on fibrosis level. On the second point, he notes that several papers looked at major genotypes like PNPLA3 and HD17N13 and specifically cites a late-breaker from Arun Sanyal indicating that g-allele status may impact MASH independent of weight or insulin. Michelle mentions a recent paper in Nature identifying distinct clusters of patients based on how their SLDs progress over time, with a two-cluster solution indicating patients with concomitant diabetes and obesity vs. those without these two concomitant diseases. Roger shares a key point from each paper on treatment in the US. Data in the PNPLA3 paper might suggest that the course of disease in Hispanics, who have high levels of g-allele abnormalities, might be different from other ethnic groups with far lower abnormality rates. He also notes that the faster disease progression in the non-metabolic cluster highlights the importance of learning more about Lean MASH and how to treat it, since faster progression of disease suggests later diagnosis and higher morbidity, mortality and treatment costs levels.…
1 S5 - E26.3 - Looking Back at #TLM2024 - FGF-21 Agents and the FDA Corner 13:18
13:18 Putar Nanti Putar Nanti Daftar Suka Menyukai13:18
Putar Nanti Putar Nanti Daftar Suka MenyukaiIn this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews the late-breaker presentation on efimosermin, a q4w FGF-21 agent and the "FDA Corner" session. Jörn begins the discussion by highlighting a paper from the later breaker session on efimosfermin alfa, an FGF-21 agent dosed q4w. He notes that after only six doses (24 weeks), efimosfermin alfa demonstrated significant increases in fibrosis regression and lowering NAS score. To Jörn, this result, coupled with others on efruxifermin and pegozafermin, suggest that FGF-21s are likely to play a significant role in MASH therapy once approved. After Roger and Mike note their enthusiasm about the drug class and this study, Jörn mentions a study with 96-week efruxifermin that data demonstrates prolonged efficacy. As he points out, this matters because while studies of an earlier FGF-21 candidate suggested that antibodies might develop in FGF-21 therapy, that does not appear to be an issue here. Mike asks the group why they feel placebo performs so well in clinical trials. Jörn suggests that working with a compassionate clinical care team in dealing with the patient leads to better performance on diet and exercise and, as a result, increased placebo response to what we might find in general community practice. Michelle praises the FDA Corner session, particularly the agency's transparency and willingness to engage industry and academia in finding paths to move away from biopsy. She also notes some of the practical challenges inherent of moving away from biopsy using data from earlier trials with an outmoded histology reader setup. She is optimistic about the scientific community coming together to address these issues. Jeff praises the agency for an "amazing" session.…
1 S5 - E26.1 - Looking Back at #TLM2024 - Semaglutide Passes the ESSENCE Test 13:32
13:32 Putar Nanti Putar Nanti Daftar Suka Menyukai13:32
Putar Nanti Putar Nanti Daftar Suka MenyukaiIn this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews the ESSENCE trial, the Phase 3 trial demonstrating that semaglutide regresses fibrosis levels in some MASH patients. The conversation begins with each panelist sharing a word or short phrase they felt best captured their feelings about TLM2024. Next, panelists review the meeting's most consequential paper, the ESSENCE Trial. Naim starts by describing ESSENCE, a Phase 3 trial with semaglutide demonstrating significant levels of fibrosis regression in non-cirrhotic MASH patients. Jörn adds the hopeful note that NITs performed as well as or better than biopsy in this trial, which he hopes will speed the transition in diagnostic approaches and tools. Jeff and Mike agree that from the patient's perspective, ESSENCE will be seen as a milestone in MASH therapy: the proof that a second drug can succeed in MASH. As the conversation ends, Roger notes that approval of a second agent for a particular disease often leads to dramatic growth in overall drug treatment by changing the pivotal question from whether to treat with a drug to which choice to prescribe.…
1 S5-26 - One Month Later: Looking Back at MASLD/MASH Coverage From The Liver Meeting 2024 1:11:25
1:11:25 Putar Nanti Putar Nanti Daftar Suka Menyukai1:11:25
Putar Nanti Putar Nanti Daftar Suka Menyukai00:00:00 – Surf’s Up: Season 5 Episode 26 - Last month, close to 8,000 hepatology stakeholders convened in San Diego for The Liver Meeting 2024. Hepatology Key Opinion Leader Naim Alkhouri, Novo Nordisk International Vice President for Medicines Michelle Long, and patient advocates Jeff McIntyre from the Global Liver Institute and Michael Betel from the Fatty Liver Alliance join Jörn Schattenberg and Roger Green to discuss highlights. 00:03:23 - Introduction and Groundbreaker - Highlights include recent travel, cultural events, and the Third Annual Primary Care Summit from the Fatty Liver Alliance. 00:11:35 - Describing TLM2024 - Participants shared a word or short phrase they felt best captured their feelings about TLM2024. 00:14:51 - The ESSENCE Trial - Naim starts the session by describing ESSENCE, a Phase 3 trial of semaglutide in non-cirrhotic MASH patients, which he describes as "the most exciting news of the meeting." Panelists describe the benefits of this trial from a variety of perspectives. 00.22.49 - A Challenge to Trial Recruitment? - Roger asks the group whether the presence of two approved MASH medications that do not require biopsy will make recruiting clinical trials that require them more challenging. The group doubts this will not add a significant new challenge to already-challenging trial recruitment. 00:29:22 - Other keys in drug development - Naim begins a discussion of two topics: the value of synergy between resmetirom and the GLP-1 agonist, and the importance of different genetic polymorphisms in predicting the impact of drugs on specific patients. Michelle mentions a recent paper in Nature identifying distinct clusters of patients based on how their SLDs progress over time. Roger identifies two particular challenges in this area, one posed by Lean MASH and the other specific to Hispanics in the US. 00:34:42 - FGF 21s - Jörn highlights a paper from the later breaker session on efimosfermin alfa, an FGF-21 dosed q4w. Roger and Mike comment. To Jörn, this and other studies demonstrate the place FGF-21s are likely to have in MASH therapy. 00:40:29 - FDA Corner and the Role of Surrogates - Michelle praises the FDA Corner session, particularly the agency's transparency and willingness to engage industry and academia in finding paths to move away from biopsy. She is optimistic about the scientific community coming together to address these issues. Jeff notes the pivotal role he believes patients must play in this process. 00:48:33 - Patient Insights - Mike describes a poster he presented (and was lead co-author), titled Patient Voice in MASH Initiatives: Foundational Principles for the Conduct of Patient-Centric MASH Research . He lists the groups participating in this broad effort and the foundational principles that emerged. Michelle and Jörn share their thoughts on which principles have the greatest impact on them in clinical research. Jeff praises a panel that Mike co-chaired on Lifestyle Management of MASLD and MASH . He praises the breadth and quality of speakers and topics. He also comments on the large number of providers and industry executives who attended this patient-centered session. Roger notes a similar distribution of attendees at the Health Livers, Healthy Lives session on building momentum for prevention. 00:58:36 - Wrapping Up - Roger comments on the breadth of modes of action that have produced successful Phase 2/3 trial results. He notes that we may have 4-5 different modes of action available five years from now. In the rest of the session, panelists describe what they believe will be different and exciting at TLM2025. 01:06:01 - Question of the Week Listeners and readers, What do you consider the most essential paper or theme of TLM2024?? 01:06:38 - Business Report Changes coming in 2025 with SurfingMASH v2.0…
1 S5 - E25 - Reviewing Expert Recommendations on the Use of Resmetirom 42:02
42:02 Putar Nanti Putar Nanti Daftar Suka Menyukai42:02
Putar Nanti Putar Nanti Daftar Suka Menyukai 1 S4 - E24.5 - SurfingMASH Question of The Week: Keys to Improving Provider-Patient Communication 20:14
20:14 Putar Nanti Putar Nanti Daftar Suka Menyukai20:14
Putar Nanti Putar Nanti Daftar Suka MenyukaiTwo weeks ago, the SurfingMASH Question of the Week asked, "What structural or educational changes do you anticipate will significantly improve Provider-Patient communication? Will these changes require more from the provider and more from the patient?" Today, S5 E23 panelists Mike Betel and José Willemse join Roger Green to review the three answers we received. Of the three questions from audience members, one from a patient/patient advocate suggested greater honesty, better listening, and, if possible, either longer appointments or better care team engagement. The second, from another patient, discussed being more honest about the Quality of Life impact of immunological drugs, along with ways to manage these drugs better. The third, from a public health official in Argentina, discussed increasing the use of multidisciplinary teams to educate and empower individuals around healthy habits and lifestyles. To Mike, these answers all convey the need for "tailored care," a care and engagement process suited to each patient's individual situation in terms of disease(s) and quality of life needs and issues. He also suggests that pharmaceutical companies help educate physicians on these issues while discussing the disease and use of their medicines. José notes that it might not be possible to get more time for a visit, but the physician could improve the visit immensely by asking patients true open-ended questions about their feelings and concerns and then actively listening to their answers. She also suggests that physicians not act like they are time-compressed. If physicians act more leisurely, patients will be more comfortable, even if they do not take up more time. Roger suggests that the format of physician protocols and instructions might be part of the problem. If the physicians are evaluated by their employers based on their ability to work through an entire checklist in 15 minutes, they will focus first on the clock and second on the checklist. This will not leave time for patient questions and, even worse, will leave the patient afraid to take up any more of the physician's time than is necessary. Thus no true communication develops. Mike goes back to a point that José made during the original episode: physicians should close their computer screens and look at the patients. Roger goes back to the question about immunosuppressants to ask whether providers can assess patients' abilities to manage medications that cause or exacerbate depression and then offer advice and perhaps antidepressants as appropriate. Given all these emotive patient needs, José suggests that patient support groups have tremendous value, and Roger notes the presence of online support structures like HOPE from Sober Livers (Season 5 Episode 18). After asking where to find resources for these kinds of activities (particularly in less wealthy parts of the world), the conversation ends.…
1 S5 - E24.4 - EASL Congress Six Weeks Later: Jeff McIntyre's Key Implications for GLI 18:28
18:28 Putar Nanti Putar Nanti Daftar Suka Menyukai18:28
Putar Nanti Putar Nanti Daftar Suka MenyukaiIn the second half of Roger Green's interview with Global Liver Institute Vice President, Liver Programs Jeff McIntyre, Jeff discusses the implications of his key EASL Congress takeaways for GLI and other patient advocacy groups. To Jeff, this trend makes patient advocates a more valuable player in the clinical trial design process, particularly when coupled with the FDA's increasing focus on diversity in trial populations. This will become particularly important because, today, the major use of incretin agonists like semaglutide and tirzepatide is in anti-obesity, where payers are frequently declining to pay for the drugs. Advocates like GLI will be pivotal in ensuring that patients who need MASLD drugs will still get the drugs they need, particularly at earlier stages of fibrosis. This discrimination may allow patients to receive incretin agonists during the pre-fibrosis stage based on diabetes and anti-obesity medications and reserve the fibrosis drugs for patients with more advanced MASH. The entire scenario of early metabolic, later MASH treatment with different agents is at least 4-5 years in the future. In the meantime, Jeff sees a need to advocate for underserved groups in the population while at the same time laying the foundation for the longer-term case. In this context, the United Nations General Assembly side effect (covered in S5, E22) is an exciting and vital event.…
1 S5 - E24.3 - EASL Congress Six Weeks Later: Jeff McIntyre's Key Takeaways 12:46
12:46 Putar Nanti Putar Nanti Daftar Suka Menyukai12:46
Putar Nanti Putar Nanti Daftar Suka MenyukaiThis conversation contains the first half of Roger Green's interview with Global Liver Institute Vice President, Liver Programs Jeff McIntyre, during which the two discuss what Jeff considered the key strategic takeaways for GLI from the various EASL Congress presentations, abstracts and discussions. Jeff focuses on the "overriding sense of optimism" coming from the multiple pieces of positive drug data. He cites the data on Boehringer Ingelheim's survodutide, the follow-up work on Madrigal's resmetirom, an anticipated presentation on semaglutide at the AASLD in November, and strong FGF-21 results as proof that we are beginning to develop multiple robust, safe and effective modes of action for drugs to treat (at least pre-cirrhotic) MASH. His second positive point is that due to the drug trials and nomenclature change, GLI and other advocates are starting to have "more enlightened discussions" about MASLD in the context of the whole patient and related metabolic conditions. As a result, he comes to the third point, which is that multiple modes of action will teach us why what works in one patient might not in another and, ultimately, reshape clinical trials so that the target might not be fibrosis (or at least not only fibrosis), but instead exactly how each drug works. Jeff envisions this line of inquiry as a step down the path away from requiring biopsy.…
1 S5 - E24.2 - EASL Congress Six Weeks Later: Mathieu Petitjean's Key Implications 10:58
10:58 Putar Nanti Putar Nanti Daftar Suka Menyukai10:58
Putar Nanti Putar Nanti Daftar Suka MenyukaiIn the second half of Roger Green's interview with PharmaNest Founder and CEO Mathieu Petitjean, Matt discusses the implications of his key EASL Congress takeaways for PharmaNest. Matt starts this discussion with a simple question: Will biopsy-based analyses become part of a surrogate endpoint? As he points out, they are not today, and creating the necessary data might require a significant effort. If not, they are unlikely to remain relevant to the large, Phase 3 trials. Regardless of the answer to this question, Matt believes digital pathology will still be important in pre-clinical work and other efforts to define underlying liver structures and faults better. Also, he notes, digital pathology is valuable in an array of other liver diseases and in non-hepatological markets, notably including pathology. One way or another, he is confident PharmaNest will continue to make contributions to hepatology and grow as a business.…
1 S5 - E24.1 - EASL Congress Six Weeks Later: Mathieu Petitjean's Key Takeaways 17:10
17:10 Putar Nanti Putar Nanti Daftar Suka Menyukai17:10
Putar Nanti Putar Nanti Daftar Suka MenyukaiThis conversation contains the first half of Roger Green's interview with PharmaNest Founder and CEO Mathieu Petitjean. After Matt tells the audience a little about his background and PhramaNest, the two discuss what Matt considered the key strategic takeaways for PharmaNest from the various EASL Congress presentations, abstracts and discussions. Before answering the question, Matt describes the core services his company offers: "PharmaNest specializes in digital pathology. Four years ago, we put down the hypothesis that the histological phenotype of fibrosis should be quantified in a high-resolution, sophisticated way." He goes on to state their core proposition for MASLD: "The big idea here is that fibrosis equals phenotype." He proceeds to describe his offerings in greater detail before offering the underlying value of computed histology: fibrosis is a continuous variable that is scored in discrete categories under the NASH-CRN model that drives FDA analysis. With this as context, he answers the question by describing three kinds of MASLD clinical trial designs. The first, earliest trials had a single pathologist reading histological slides. The method is not precise, but the drugs were not very good, and none were ultimately approved. The second set of trials relied on more rigorous methods for pathologists to read histology slides, with multiple readers and robust adjudication systems. Also, the drugs in this second set of trials were more efficacious, so that NASH-CRN, while a blunt instrument, could adequately assess efficacy. For the third set of trials, Matt believes non-invasive tests (NITs) are likely to suffice.…
1 S5 - E24 - A view of MASLD: Looking back at EASL Congress from six weeks later 1:16:26
1:16:26 Putar Nanti Putar Nanti Daftar Suka Menyukai1:16:26
Putar Nanti Putar Nanti Daftar Suka Menyukai00:00:00 - Surf's Up: Season 5 Episode 24 This week's episode on MASLD lessons from the EASL Congress 2024 includes three separate elements: individual interviews with PharmaNext Founder and CEO Mathieu Petitjean and Global Liver Institute Vice President of Liver Programs Jeff McIntyre, followed by a discussion with patient advocates Mike Betel of the Fatty Liver Alliance and José Willemse from the Netherlands, now supporting EASL. 00:02:45 - Introduction Roger explains the episode format, including the two key questions for Mathieu and Jeff: (i) what were their key takeaways from the EASL Congress, and (ii) how have those takeaways changed how they do their jobs or plan for the future? Roger also sets up the Question of the Week discussion that is today's third section. 00:04:04 - Meet Mathieu Petitjean This is the SurfingMASH debut for Mathieu Petitjean, Founder and CEO of PharmaNest. He tells the audience a bit about his background and his love of Harleys. 00:07:10 - First question to Matt Matt begins by describing the core services Pharmest, a digital pathology company, offers MASH drug developers. Then he answers Roger's question by describing three phases in MASLD clinical trial designs. His point is that over time, drugs have gotten better, and histology requirements have become more onerous. At some point in the not-too-distant future, Matt believes non-invasive tests (NITs) are likely to suffice in large Phase 3 trials of the future. 00:21:01 - Second question to Matt Matt starts the answer with a conditional: if biopsy-based analyses become part of a surrogate endpoint, the role is large and clear. If not, they are unlikely to remain relevant in Phase 3 trials. Regardless of the answer to this question, Matt believes digital pathology will remain important in pre-clinical work and in other continuous liver diseases with less-defined targets. Also, he says, digital pathology is valuable in an array of non-hepatological markets, notably including pathology. 00:29:11 - First question to Jeff Jeff describes an "overriding sense of optimism" he felt due to the many positive drug trials presented in Milano. This suggests that the MASLD community is developing safe and effective MASH drugs with many different modes of action. This is allowing GLI and other advocates to start to have "more enlightened discussions" about MASLD in the context of the patient's overall metabolic state. All this means that what works in one patient might not in another. This can reshape clinical trials so that the endpoint target might not be change in fibrosis but impact against specific NIT targets. Jeff envisions this line of inquiry as a possible step away from biopsy. 00:39:34 - Second question to Jeff Concurrently, FDA is beginning to require greater diversity in clinical trial populations. To Jeff, all this makes patient advocates like GLI more valuable to the clinical trial design process and pivotal in ensuring that metabolic and advanced MASH patients will still get the drugs they need. Starting today, Jeff sees advocates as championing underserved groups in the population while at the same time laying the foundation for the longer-term case. 00:55:20 - Discussing previous "Question of the Week" This is a 15-minute discussion of the Question of the Week we posed at the end of S5 E23. This section will constitute S5 E24.5, which we will post in the next day or two. A more complete summary will appear there. 01:11:23 - Question of the Week The Question of the Week is the first question Roger asks Matt and Jeff during this episode. 01:12:58 - Business Report Previewing Episode 25, with Maru Rinella discussing the recently-published expert recommendations on use of resmetirom, along with comments on office hours the reason we will not have a vault conversation this week.…
1 S5 SPECIAL 5 - Reviewing EASL Congress: Louise Campbell 3 (first-time material) 9:48
9:48 Putar Nanti Putar Nanti Daftar Suka Menyukai9:48
Putar Nanti Putar Nanti Daftar Suka MenyukaiThis week, Surfing the MASH Tsunami looks back on interviews Roger Green conducted during the EASL Congress itself. This conversation with SurfingMASH co-host and Tawazun Health Founder and Clinical Director Louise Campbell took place on the last day of the Congress This portion of the conversation was not included in the original S5 E19 but instead was reserved for a special conversation at a later time (now). The specific focus of this conversation is on how practice patterns and guidelines are likely to change over the next several years. One driving factor involves the need to get primary care not only involved but actively committed to playing a leading role in treatment, given how quickly the identified patient population might grow. Louise points out that the overall rate of growth might be one longer-term issue, but in the short term, dramatic increases in the number of patients with cirrhosis will be a more immediate concern. She questions how staffing and training will address both challenges, with more patients being diagnosed in earlier-stage MASLD patients, coupled with more late-stage fibrosis and cirrhosis. She speaks specifically about a poster looking at liver disease as a factor for cardiac arrhythmias and the seemingly confounding idea that play three, while a genetic target to predict muscle, might also be cardioprotective within the muscle population. However, it has no effect on muscle progression or other just related diseases. This leads Louise to one more optimistic conclusion this time that we will see broader collaboration between specialties over time as we appreciate the scope and complexity that comes from viewing muscle as part of the broader metabolic disease continuum.…
1 S5 SPECIAL 4 - Reviewing EASL Congress: Sven Francque 17:12
17:12 Putar Nanti Putar Nanti Daftar Suka Menyukai17:12
Putar Nanti Putar Nanti Daftar Suka MenyukaiThis week, Surfing the MASH Tsunami looks back on interviews Roger Green conducted during the EASL Congress itself. This conversation with Hepatology Key Opinion Leader and EASL Educational Councillor Sven Francque took place 90 minutes after the EASL Congress closed. The discussion focuses on plans and hopes for the future, both the future of MASLD diagnosis and treatment and of the EASL Congress itself. The conversation starts with Sven discussing all the positive energy coming from the Congress, not only for MASLD but for the entire Liver community. He describes the ambiance of the meeting as feeling "vibrant," and with a lot of interaction. He goes on to discuss the CPG guideline committee on which he was a member. (See Season 5 Episode 21 for a fuller discussion of CPG). Sven goes on to share the vision of disease that led to this broad, forward-looking guideline update. From there, we discuss positive results from a set of early-stage clinical trials, with Sven commenting specifically on tirzepatide, efruxifermin and an array of positive phase two trials, one of which is lanifibranor, which presented its results previous year. Sven also finds two studies that use different methodologies but evaluated the prognostic value of liver stiffness to be important. He discusses the value of the new nomenclature and how it allows researchers to look more broadly at the entire steatotic liver disease category. We close by talking once more about the positive body of drug development studies, which Surfing MASH discusses in greater detail in Season 5 Episode 20.…
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