So far, this conversation has focused on Rezdiffra approval and its many forms of impact on MASLD patient advocates. This conversation considers their recommendation for others.  The conversation starts with Roger Greens final question. He asks each panelist to identify a stakeholder group that can take a valuable lesson from this episode and what that lesson should be.  Wayne Eskridge goes first. Wayne focuses on the need for Madrigal and the various professional societies to increase education and information support for the gastrointestinal community.  Mike Betel and Jenn Jones hope the Rezdiffra approval will lead to greater research investment and a broader, deeper focus for their investments. Louise Campbell returns to the need for provider education, this time for medical nursing and allied health professionals. She also believes organizations need to recruit greater nursing capacity.  Jeff McIntyre asserts that if nutrition and physical activity are critical adjuncts to drug therapy, the entire healthcare community needs to advocate for access and reimbursement to dieticians, physical therapists, exercise specialists, and other supportive professionals. Tony Villiotti returns once more to education, mentioning the need to increase scale. He also discusses some specific topics that will merit more focus.  Finally, Roger Green discusses two different forms of optimism: optimism among patients that they can be treated and, separately, optimism among investors that increasing the scale and scope of their investments will provide good returns.  

9m

Mar 24

This conversation asks what impact Rezdiffra patient education might have on a U.S. healthcare system in which 38% of American adults live with some form of MASLD and 15% live with MASH.  Louise Campbell starts off by saying she is “slightly fed up” with the idea that we cannot proceed too quickly for fear of overwhelming the system. Louise would rather flip focus to push systems to build the capacity they will need to handle the flow of patients that will certainly grow over time. Mike Betel agrees and discusses two Fatty Liver Alliance activities in Canada, one of which is a survey of 27,000 primary care physicians.  Roger Green pushes back slightly on Louise’s comment about overwhelming the system. He suggests that building capacity may be easier in countries with government-run healthcare systems, where one group can make and implement national decisions, than in the fragmented private US system where everything is measured in terms of short-term profit.  Jeff McIntyre agrees with Louise’s point in that we can’t think in terms of “don’t burden the provider anymore.” He then discusses an innovarite solution the US Veterans Administration is implementing. Louise points to the importance of systems solutions in view of her belief that most patient management in MASLD will fall to primary care within the next 5-7 years. This stresses the importance of systems enhancements and growing the population of advanced providers. 

11m

Mar 24

This conversation focuses on how the role of MASLD patient advocates might change and expand in the aftermath of Rezdiffra being approved.   To Wayne Eskridge, this “raises an entirely new field of education and outreach,” because now advocates can do more than merely be supportive emotionally. Advocates can, quoting again, “refresh our message and have broader perspectives and share a more hopeful outlook to the future” and talk about clinical trial participation and other drugs coming down the line. Also, he notes that advocates can provide the education to bring new patients into the system and help deliver the information providers will need to know in order to treat them. Jeff McIntyre adds that this will raise a new set of questions for advocates to ask companies and the healthcare system in terms of support for patients with cirrhosis, more patient-friendly dosing, reimbursement…a range of issues.  Roger Green shifts focus to ask how advocates can help slow the flow of patients into the system by reducing the rate of MASLD growth. Tony Villiotti says education is key and notes how NASH kNOWledge starts by educating children. Jenn Jones adds that education and promotion can give hope to patients with alcohol-related liver disease and those with the new category MetALD. She also notes that the label gives advocates new leverage to stress the importance of nutrition and physical activity. 

11m

Mar 24

This conversation focuses on the steps that patient advocates took to educate the FDA on what patients wanted in a MASH drug label, in this case for Rezdiffra.  It starts with Jeff McIntyre reflecting on apparent changes in how the FDA thinks about labeling since the initial obeticholic acid Complete Response Letter in 2020. His specific point: since that first CRL, GLI has worked closely with patient advocates, including those on this call, to educate the FDA on what their endpoints and considerations were around safety and efficacy and to help get Rezdiffra approved in the way that brings maximum benefit to patients. He points to biopsy as one proof point. More important, he believes the advocacy from patients has led to an approval process and label that “de-risks” the MASLD space for future investment.  The other panelists agree. Wayne Eskridge points back to biopsy as a particularly critical issue. Jenn Jones believes the collective effort has improved accessibility as well. Tony Villiotti acknowledges a concern that the FDA had been “dismissive” during the Obeticholic Acid Advisory Committee last year and describes himself as “pleasantly surprised” by the patient centricity of the final Rezdiffra label. Louise Campbell says this label might become a “game changer” if it signals that Madrigal will help MASH patients, most of whom live with co-morbidities, get support in navigating their array of issues. As the conversation ends, Roger Green makes a specific point that Madrigal’s offer to support medical exceptions signifies a deep understanding of the actual challenges to early uptake and a commitment to do better than companies in the past.

10m

Mar 23

This conversation focuses on advocates reactions throughout the day on Thursday, March 14, the day Rezdiffra became the first MASH drug approved in the U.S.  Specifically, panelists discuss their thoughts and feelings as they reflected on Rezdiffra’s approval in the context of their personal experience. While no panelist is eligible to receive Rezdiffra as indicated, some thought back that day on their earlier patient experiences, while others thought of the patients for whom they advocate.  During the day, all the panelists describe themselves as having reflexively refreshed their screens, waiting for news, and a few described real concern over seeing the announcement that morning from AASLD withdrawn a little while later. Once the announcement came out officially, reactions varied. Wayne Eskridge was the first to reflect on his reactions. He recalled his initial diagnosis in 2014 or 2015, a “very emotional” event in his office because, at that time, the diagnosis sounded like a death sentence. Tony Villiotti says the approval did not resonate with his experience, but that he felt a surge of hope for those who might benefit today and in the years ahead. Mike Betel seconds his statement, mentioning that the lack of a biopsy requirement was an excellent benefit for patients. Jenn Jones likes the idea that the drug is non-invasive and believes "this is the start of a new era" for MASLD patients of all kinds.

13m

Mar 23

This conversation focuses on two issues: (i) identifying the right target MASH patients for Rezdiffra, and (ii) the extensive Madrigal patient support program for Rezdiffra. It starts with Roger Green asking the group how the current set of target patients is defined. Jeff McIntyre points out that these are the patients currently treated for F2 or F3 MASH in the US healthcare system. Roger asks if this is analogous to the idea of “warehoused” patients observed in Hepatitis C. Jeff suggests these are quite different from warehoused patients in that warehoused patients are not being treated at all, whereas all the target MASH patients are engaged in some form of treatment.  Next ,Roger notes that Wayne Eskridge published a long post earlier in the day about the extensiveness of the Madrigal patient support program. Wayne discusses the program in some detail, in the process explaining why this process appears likely to be more engaged, interactive and helpful than the typical patient portal program.

9m

Mar 23

Last Thursday, March 14, REZDIFFRA (resmetirom) became the first drug approved in the US for MASH. Five leading North American MASLD patient advocates join the Surfers to discuss their feelings about this approval along with the opportunities and challenges that lie ahead. 00:00:00 - Surfs Up: Season 5 Episode 7 Opening introduction from an excited, enthusiastic panel, including brief quotes taken directly from the episode discussion. 00:05:55 - Groundbreakers Each panelist shares one piece of good news from the previous week. 00:11:19 - Advocates recall March 14 As March 14 progressed, advocates attitudes moved from excited anticipation to anxiety to deep happiness. 00:17:41 - Advocates describe their feelings as patients None of these advocates are Rezdiffra candidates themselves, but each reflected on their personal experiences with MASLD and what the future holds for patients who are or will be candidates for Rezdiffra. 00:22:33 - Identifying target patients This conversation starts with Roger Green asking the group to describe where the number "315,000 target patients" came from. After the group replies, Jeff McIntyre and Louise Campbell explain how this is different from a "warehoused" patient population, and Wayne Eskridge discusses the exciting, progressive Madrigal patient support program. 00:29:53 - The advocates role today Jeff begins this discussion by emphasizing the role GLI has shepherded and advocates have played in informing FDA about patients key concerns for the label. He describes how these are reflected in the approval decision and label, with biopsy being the most obvious example. The other advocates agree, with Mike Betel emphasizing how closely the leading advocates co-ordinate with GLI and each other. Louise suggests it will be a "game changer" if FDA takes a similar view to labels for other metabolic diseases. Roger points to Madrigals discussion of medical exception as proof of their commitment. 00:37:10 - The advocates role tomorrow Advocates agree that this approval creates new, broader opportunities for education and outreach. To Jeff, the approval will allow advocates to ask bigger questions on emerging needs. He offers treatment for cirrhosis and drug reimbursement as two such areas. 00:41:22 - Slowing the patient flow Roger asks what steps advocates can take to slow the flow of patients through the progressive stages of MASLD. Tony Villiotti notes that this is the primary goal of NASH kNOWledge, starting with childhood education. Jenn Jones states that publicity about Rezdiffra may lead patients with MetALD or ALD to explore how they can protect their own livers and seek early detection. 00:46:15 - Overwhelming the system Louise describes herself as "slightly fed up" at individuals who  fear "overwhelming the system." Instead, she says, systems should build capacity to reflect the scale of the disease. Roger notes this may be harder to execute in the US than in countries where governments control their healthcare systems. Jeff points to the US Veterans Administration as a possible model for ways to build capacity.  00:52:21 - Emerging role of primary care Louise states that much treatment will shift to primary care over the next 5-7 years.  Roger agrees and seconds Jeffs comments about the role the VA can play. 00:54:55 - Closing question Roger asks each panelist to identify a healthcare stakeholder group that needs to take a lesson from the issues discussed today. Answers vary widely. 01:02:06 - Question of the Week The question asks what good ideas listeners have for other stakeholder groups in the aftermath of REZDIFFRAs approval. 01:02:54 - Business report This weeks news on audience metrics, future episodes and why there will be no Vault conversation again this week

1h 5m

Mar 21

As the conversation wound down, Roger Green offered panelists to address any issue pertaining to Rezdiffra, the first MASH drug, that had not come up in the hour-long conversation.  The seven panelists raised eleven exceptionally diverse issues between them. Rather than provide a simple list of issues, the co-hosts invite you to listen to this short conversation to gain a fuller appreciation of each point.

8m

Mar 19

This conversation revolves around one question: "What lessons should the BioPharma industry take from the launch of Rezdiffra?" Answers revolve largely around clinical trial design and, generally, taking a broad, long-term view of what the trial must accomplish to optimize drug adoption. More specifically, Roger Green starts this conversation by noting that much of the SurfingMASH audience works in pharma or biotech. He asks what lessons they should take from this experience. Zobair Younossi responds first, commending Madrigal for “doing the right thing” and being persistent for years, even when it appeared that Rezdiffra would come to market years after the anticipated first drug. To Zobair, "the right thing" includes conducting multiple trials at different diseases and targets, including large samples in each trial, and introducing NITs as endpoints. Jeff McIntyre also feels that using NIT markers to parallel biopsy in clinical trials has created a major bridge to an all-NIT, post-biopsy initial diagnosis plan. Louise Campbell asks what impact the two-day NIT workshop the FDA conducted last autumn had on any of this. Zobair, who works closely with the FDA, suggests that the agency is taking time to process this information collaboratively. He believes the agency is moving in the right direction, if more slowly than we might like.

7m

Mar 19

One pivotal question surrounding the launch of Rezdiffra is "Which MASH patients are the correct targets for the first MASH drug?" This conversation focuses on the tools and education the health system will need to locate these patients and have them treated by the appropriate prescribers.   The conversation starts by considering educational goals. Zobair Younossi asks what is practical and proceeds to answer his own question.  He starts by pointing out that most early patients will be found in GI practices. This presents a challenge. While hepatologists and their advanced providers have the knowledge they need to identify patients and prescribe, most of the target patients are being treated in gastroenterology practices, and this group is not as knowledgeable about the disease, screening, staging and treatment. For 2024, he says, educating this group must be the primary focus of education. Zobair notes that other specialty organizations are aligned with the need to screen, stage and treat, but the lay practitioners in these specialties also will need education.  Jeff McIntyre agrees strongly with Zobair’s assessment. Jeff asks: education to what points or outcome? Jeff views education as needing to address two issues: proper prescribing and use of the drug, but also proper identification of patients. To Jeff, these are the key needs in educating gastroenterologists and their advanced providers, but also key issues for educating patients so they can advocate effectively for themselves.  Jörn Schattenberg states that Rezdifra’s safety profile is a critical benefit. It alleviates some concern that a well-meaning provider might prescribe for a patient with compensated cirrhosis due to a lack of precision with current tests.  Roger Green notes that the excellent Rezdiffra safety profile will resolve a dilemma physicians have with most first-in-class drugs: how to do no harm while getting the drug to the right patient. This safety profile makes the dilemma less profound, although it is no less important to keep in mind.  Returning to education, Laurent Castera closes this conversation by noting that he works at a “liver clinic inside a diabetes clinic,” and that the diabetes screening protocol—an annual FibroScan for every patient with suspected advanced liver disease, followed by referral to a hepatologist—is working well. 

12m

Mar 19

This conversation focuses on the necessity of using NITs to screen and identify Rezdiffra patients, while at the same time acknowledging the shortcomings of current tests. Panelists suggest some different NIT testing strategies while commenting on upsides and potential challenges for each MASH NIT. Laurent Castera joins the conversation at the beginning, which is helpful given his extensive research and knowledge of the surrounding communities. Laurent points out that distinguishing F3 patients from F4 will be a difficult challenge to solve, in part because we used categorical scores for fibrosis instead of recognizing that it is, in fact, a continuum where, in Laurents words, "you are not 1.2 or 1.5. Youre F1, 2, 3 or 4." Having a drug will facilitate a shift from the old-school categorical view to a more linear one.   Laurent goes on to comment that it is not clear exactly how we will use NITs, but that liver stiffness will certainly be one key metric, one he describes as "a prediction scale." He also comments on the problems caused by relatively low arbitrary cutoffs here, 12.25) and the need for (a) repeat measures and (b) use of at least two tests. He mentions platelet counts as one important example.   Jörn Schattenberg discusses the importance of clinical observation and judgment. Zobair Younossi takes that point further to stress the importance of conservative judgment in assessing for cirrhosis. Laurent suggests that a second, "more specialized test" that is "not related" to VCTE will tremendously improve accuracy.  I comment that one important issue is that individual prescribers will now start treating with Rezdiffra and will derive opinions about the drug based on their experiences with the first few patients for whom they prescribe. I suggest that similar patterns may be true for NITs and ask how panelists anticipate providers will receive education on NITs.  Louise Campbell talks about the roadmap that Madrigal showed of what theyre going to have their reps and MSL trained doctors on and believes that will be exceptionally helpful. She also feels it is vital that practitioners early in the patient visit change also be well-educated on this topic. She notes that many of the people focusing on this topic, including former panelist Suneil Hosmane, now at Madrigal, are first-rate.  Jeff McIntyre closes the conversation by suggesting there will be a "huge patient role," because patients are people who can demand, or at least ask questions of doctors that will lead the doctor to do things they might not otherwise and to get more informed on related issues. Jeff notes that we have not come up with an adequately specific answer to the question, "Whats the best NIT?" which mandates that we keep educating and speaking out.

15m

Mar 18

* This conversation focuses on what panelists see as a key (and somewhat unusual) benefit of Rezdiffra: that having a prescription drug for MASH creates a better environment for discussing lifestyle intervention and improving overall patient adherence with diet and exercise.   This conversation focuses on the impact of having a drug on getting patients to comply with lifestyle interventions. Zobair Younossi starts by noting that, historically, it has been "very difficult" to institute successful lifestyle interventions because patients "are not used to thinking about lifestyle as a prescription." Now, providers can counsel patients to adhere to a regimen that includes medication lifestyle changes.   Jörn Schattenberg notes that Rezdiffra is indicated in the label as an adjunct to diet and exercise, which is common wording for most metabolic drugs. Zobair agrees but notes that this is still difficult to achieve in practice. One example: in the US, not everyone can comply with the idealized Mediterranean diet. As he notes, diet recommendations must be geographically and culturally relevant. I note that in my 25 years of marketing research, one thing I learned was that physicians feel they "have nothing" when all they can offer patients is lifestyle modification. With a drug in the discussion, the provider can "flip the script" to make lifestyle intervention adjunctive to the drug.  Jeff McIntyre points out specifically that having Rezdiffra to prescribe will help reduce stigma by "medicalizing" the recommendation to lose weight and add exercise. In effect, Jeff says, this takes the onus off the patient to feel responsible for their own disease. Zobair discusses a recent publication from the Global MASH Council on the impact of stigma.   At this point, Laurent Castera joins the conversation.  He adds the thought that having a drug to prescribe will increase interest among primary care providers. He also notes the importance of the label coming without a biopsy requirement, "a very important message to convey."  The conversation ends with Ian Rowe sharing his concern that it will be "quite difficult" to differentiate patients living with advanced fibrosis patients from those living with cirrhosis.

11m

Mar 18

FDA approval of the first MASH drug, Rezdiffra, on March 14 marked what co-host and Key Opinion Leader Jörn Schattenberg describes as a "watershed moment" for hepatology. This opening discussion covers how panelists heard the news of Rezdiffras approval, how they reacted, and their initial thoughts about appropriate patient targets. As the conversation starts, the various panelists describe their moves throughout the day on March 14th and their reactions when word of the FDAs approval came. They all describe having felt various degrees of trepidation as the day progressed. Jeff McIntyre describes him and his friends as "constantly refreshing our screens" throughout the day. Zobair Younossi probably felt less anxiety than others, while some of the Europeans described feeling more. This was replaced by excitement and joy at the final announcement. Jörn Schattenberg describes the day as a "watershed moment," that, in Zobairs words, "energiz[ed] for the entire field." Panelists go on to describe the patients they expect to prescribe Rezdiffra for at launch (now for the US, whatever comes available on the EMR). Jörn intends to prescribe initially for F3 patients but realizes he might not know exactly how to distinguish them from early-stage cirrhosis. Zobair points to prescribing for F2 and F3 patients as indicated in the label.

11m

Mar 18

Last Thursday, March 14, REZDIFFRA (resmetirom) became the first MASH drug approved in the US. A global panel of Key Opinion Leaders convenes to discuss their excitement about this approval, the opportunities it will create and some of the (largely manageable) challenges it might present. 00:00:00 - Surfs Up: Season 5 Episode 6 Opening introduction from an excited, enthusiastic panel, including brief quotes taken directly from the episode discussion. 00:05:02 - Groundbreakers Each panelist shares one piece of good news from the previous week. 00:08:15 - Waiting for news and initial reactions Panelists  describe their moods throughout the day on March 14 and reactions when word of the approval came from FDA. They describe feeling varying degrees of trepidation as the day progressed without word from the agency, replaced by excitement and joy at the final announcement. 00:14:30 - Specific patients to target or avoid Panelists describe the patients they expect to prescribe REZDIFFRA for first (now for the US, when it becomes available for EMA).  The group aligns on the benefits for F3 F2 patients (the two groups listed on the label) but shares concerns about accurate identification of F3 vs. compensated cirrhosis. 00:17:07 - Impact on explaining lifestyle interventions Zobair Younossi notes the historical difficulty of getting patients to view lifestyle modification as a specific prescription to be followed. He, Roger and Jeff all makes points to suggest  that  the combination of drug + lifestyle modification will be easier to explain to patients. 00:26:32 - Staging and screening patients using NITs Laurent Castera joins the conversation as the topic switches to proper use of NITs.  Previously, Jörn Schattenberg and Ian Rowe touched on challenges in deciding which patients have F3 fibrosis vs. early stage cirrhosis. Now the group explores the relative value of different strategies for qualifying patients. One key: while FIB-4 is an efficient screening test in largely negative populations, it produced a high level of false positives in specialty practices. 00:33:50 - How to educate providers Roger points out that individual providers will conduct individual "clinical trials" in their own practices. This makes provider education on proper use critical to launch success. Louise Campbell commends Madrigal for the education pathway they laid out during the webcast. Jeff discusses the important role patients must play. 00:39:06 - Finding the initial patients Apropos of education, Zobair points out that most early patients will be found in GI practices. Jeff points out that these patients are already in the system and can be easily identified. 00:43:12 - Why REZDIFFRAs strong safety profile matters so much Panelists that REZDIFFRAs safety profile alleviates some concern that a well-meaning provider might prescribe for a patient with compensated cirrhosis due to inadequacy of current tests. 00:48:39 - Suggested takeaways for industry Panelists suggest that industry learn from the large sample sizes and thoughtful use of NITs found in the REZDIFFRA trial protocols. 00:52:20 - FDA and NITs Louise asks how important FDAs two-day NIT workshop last year was in the agency not requiring biopsy prior to prescribing. Zobair says agency officials are moving slowly down a path toward greater acceptance. 00:53:53 - Closing Thoughts Each panelist shares a closing thought. The topics vary widely. 01:01:06 - Question of the Week The question is what impact REZDIFFRAs approval will have on individuals day-to-day work. 01:01:47 - Business report News on audience metrics, future episodes and why there will be no Vault conversation this week

1h 4m

Mar 16

This conversation comes from our first look at MASEF, last September, when lead author Mazen Noureddin joined the Surfers to discuss his recent breakthrough paper on this new NIT.  The original conversation had a robust write-up: https://pubmed.ncbi.nlm.nih.gov/37505221/#:~:text=Based%20on%2012%20lipids%2C%20body,%2DAST%20(FAST)%20score.

13m

Mar 10

After some final discussion about GLP-1s, this conversation entails Roger Green summarizing what he has heard in the episode so far and testing for confirmation or correction. It goes fast and covers significant ground.  Naim Alkhouri starts this conversation by discussing patients for whom he would prescribe resmetirom vs. GLP-1s. Lean MASH patients are likely to receive resmetirom. Earlier fibrosis patients are more likely to receive semaglutide. A multimorbid F3 patient might receive both.  Roger asks how things might change with tirzepatide, since it is a dual agonist with strong MASH-lowering effects. Naim expresses doubt that tirzepatide will be antifibrotic, since neither GLP-1 nor GIP have direct liver effects. He has more faith in the glucagon dual- and triple-incretin agonists.  The rest of the conversation involves Roger stating themes he has heard earlier and asking for confirmation or amendment. It moves pretty fast, covers a lot of territory, and receives some agreement and some correction.

11m

Mar 10

This conversation touches on two important subjects: the impact of different potential resmetirom prices on the size and structure of the treatable MASH population, and the impact GLP-1s are having (and will have) on clinical trial recruitment and basic patient treatment.  It starts with Naim Alkhouri expressing concern over the $39-52K price he has heard for resmetirom, which ICER has deemed cost-effective. He mentions another paper that says a price of $19,000 would be cost-effective. To Naim, this magnifies a question that is already quite widely considered: when to prescribe resmetirom vs. a GLP-1 agent. He discusses some patient factors that might go into his decision.  Naim describes ways that GLP-1 use, which can be sporadic or episodic, is affecting clinical trial recruitment. Ian Rowe discusses the current use of GLP-1s in the UK and suggests that if the price for resmetirom is high enough, GLP-1s will receive significant use.  Naim Alkhouri shifts direction slightly, from discussing current GLP-1s to exciting recent clinical trial report. He focuses on two: survodutide from Boehringer Ingelheim and efruxifermin from Akero Therapeutics. Recent exciting results from BI and Akero suggest to Naim and others that the future for drugs is bright.  Ian Rowe anticipates a significant amount of co-prescription of GLP-1s and resmetirom in this population. GLP-1s have already demonstrated clear cardiovascular, weight loss, and HbA1c-lowering benefits. To Ian, that creates sufficient motivation to prescribe GLP-1s to multimorbid patients with diabetes, obesity and most likely MASLD or MASH. To him, the price of resmetirom will have a tremendous impact on how often UK physicians rely on GLP-1s alone.

11m

Mar 10

This conversation focuses more tightly on the specific challenges with the current approaches that use NITs to diagnose and stage advanced MASH fibrosis and explores several newer options and ways of thinking about the challenge. Roger Green notes that recent papers discuss the failure to predict accurately with FIB-4. He asks how we can improve predictive performance. Louise Campbell notes some specific challenges, after which Jörn Schattenberg praises John Dillons work in automating lab detection algorithms. He also reiterates his view that repeat testing will be pivotal in good test protocols. Ian Rowe rejoins the conversation (from a faulty Internet connection) to comment that our inability to stage patients reliably will lead to government payers like NHS believing that they will need biopsy to stage patients accurately and treat them cost-effectively. Jörn says Germany will work differently and if EMA approves it, it will launch in Germany. Roger asks about new tests on the horizon and specifically whether there is sufficient improvement in diagnosis, staging or treatment. He refers specifically to MASEF and Naim Alkhouris earlier comments about four scan vendors at his conference. Ian says there are tests that can rise to this task, but they are not produced in sufficient quantity and cost too much to become a first-line option. Naim notes that the most exciting tests are a couple of years away. Ian returns to Jörns earlier point about the value of sequential testing vs an individual test. Louise suggests that device size will be pivotal for primary care.

14m

Mar 10

This conversation explores the challenges with using the current non-invasive tests (NITs) to diagnose patients with F2/F3 advanced MASH fibrosis. If tests today cannot achieve the requisite level of precision, panelists explore other ways to define patient targets. Roger Green starts by recalling that in a recent episode (Season 5 Episode 2 https://www.buzzsprout.com/1235408/episodes/14504051), Jeff McIntyre suggested that in the US, the initial patient population may be as small as a few hundred thousand people. Ian Rowe states that current tools are incapable of placing these patients in a narrow diagnostic or therapeutic window. Jörn Schattenberg takes a "pragmatic" approach to defining the patient he is certain to treat; test results are a small part of his calculus. Naim Alkhouri shifts the discussion to focus on VCTE cutoff points for cirrhosis. The interplay between Naim and Ian suggests that different practices and guidelines carry with them different cutoffs. Jörn expresses gratitude that the can watch the US and learn from that experience. He notes the tension between wanting a cost-effective system and large numbers of patients clamoring for the new medicine. The need to rule some patients out is obvious, the way to do so is challenging. Asking, "What can we do besides scan" or use conventional tests, Naim discusses some newer options, starting with the metabolomics-based MASEF score discussed in Season 4 Episode 39 https://www.buzzsprout.com/1235408/episodes/13501043. He also mentions the LiverFast test. Jörn describes factors that can render a test inappropriate for a particular patient. Louise suggests the right test will depend on the specific question the provider is trying to answer.

12m

Mar 10

This conversation explores why proper use of non-invasive tests (NITs) will play a pivotal role in increasing the number of patients diagnosed and treated for MASH. It becomes particularly pivotal if, as expected, the first MASH drug is approved later this month. Roger Green starts this conversation by describing why he considers NIT use and adoption one of the two pivotal patient treatment issues for 2024. Jörn Schattenberg notes that he has not received any referrals from PCPs or endocrinology based on elevated FIB-4, which would happen if enough front-line treaters were adopting the new clinical care pathways. Educational efforts have begun, but do not seem to be changing behavior yet. As Jörn puts it, "Were still preaching, and I havent seen it in much activity." Naim Alkhouri states that his experience is the same as Jörns. He reminds us that we covered some of these issues in a 2023 end-of-year conversation (S4 E50.3 https://www.buzzsprout.com/1235408/episodes/14192833). He reiterates his concern with FIB-4 as a standalone first-line test and states his preference for combining it with an in-office scan. He comments that at the recent Desert Liver Conference, four companies displayed these devices, each with a different price point and convenience factor.  Ian Rowe describes the British experience as being different: "every patient with elevated ALT in the context of metabolic risk factors has a FIB-4 and now has a FibroScan." His biggest concern is that tests are insufficiently precise. If we have top-end and bottom-end cutoffs, he fears, "youre going to end up excluding a lot of patients who would be potentially eligible for treatment."

8m

Mar 10

In 2024, the two major areas for change in diagnosing and treating MASH  are new drug approval and changes in use of NITs. Naim Alkhouri and Ian Rowe join Jörn Schattenberg, Louise Campbell and Roger Green to consider what might change with NITs and how having an approved drug might change thinking on this issue. 00:00:00 - Surfs Up: Season 5 Episode 5 Opening introduction, including brief quotes taken directly from the episode discussion. 00:02:36 - Introduction and Groundbreaker Panelists congratulate Naim on the recent, highly successful Desert Liver Conference. In the groundbreaker, each panelist shares one piece of good news from the previous week. 00:06:36 - Why Focus on NITs? Roger describes why he considers this issue worthy of an episode. Naim and Jörn both state that they have received no referrals from PCPs or endocrinology based on elevated FIB-4 tests. Ian notes that the UK has guidelines and pathways built into some protocols; these make it challenging to stage a patient as F2 vs F3 vs early compensated cirrhosis. 00:13:06 - NITs and treating F2/3 MASH patients  Ian says that current tools are incapable of defining the small nitial target patient population Jeff McIntyre suggested in Season 5 Episode 2 https://www.buzzsprout.com/1235408/episodes/14504051.  patients clearly enough to place them in a narrow diagnostic or therapeutic window. Jörn takes a "pragmatic" approach to defining the patient he is certain to treat; test results are a small part of his calculus. Naim shifts the target patient to focus on VCTE cutoff points for cirrhosis. There is no clear cutoff. 00:18:45 - Tests worth using beyond the widely discussed options Asking "What can we do besides scan" or use conventional tests, Naim discusses some the new blood-based tests. Jörn describes factors that can render a test inappropriate for a particular patient. Louise suggests the right test will depend on the specific question the provider is trying to answer. 00:22:59 - Improving on FIB-4 Roger notes that recent papers discuss failure to predict accurately with FIB-4. In the conversation that follows, panelists agree that automating test results and using a series of tests instead of a single event will both have real value. 00:28:27 - New Devices and Blood-Based Tests for Use in Office Roger asks about new tests on the horizon and specifically whether there is sufficient improvement in diagnosis or treatment. Naim notes that the most exciting tests are a couple of years away. Ian returns to Jörns earlier point about the value of sequential testing vs an individual test. Louise suggests that device size will be pivotal for primary care. 00:35:30 - Impact of Resmetirom Price Naim expresses concern over the $39-52K price he has heard for resmetirom. Roger states that price reflects size of target market. At that point, the discussion veers toward factors that drive drug prices higher. 00:40:22 - Impact of GLP-1s on treatment and resmetirom Roger asks the group what the impact of consumer-driven GLP-1 use is likely to be on US prescribing of MASH drugs. Ian discusses use of GLP-1s in the UK and suggests that if the price for resmetirom is high enough, GLP-1s will receive significant use. Recent exciting results from BI and Akero suggest to Naim and others that the future for drugs is bright. 00:47:16 - Final question This entails Roger summarizing what he has heard in the conversation and testing for confirmation or correction. It goes fast and covers significant ground. 00:53:26 - Question(s). of the Week The question is what else will change, besides prescribing, once a drug is improved and what the industry can to do optimize change. 00:54:06 - Business Report News on audience metrics, the upcoming Question of the Week, future episodes and this weeks co

57m

Mar 07

Two years ago,  conducted two episodes with Chris Estes, then the chief modeler for the Center for Disease Analysis Foundation exploring issues around CDAFs then-recent publication of a NASH/MASH disease model. This conversation centers on issues of advanced fibrosis. We thought it might be interesting to look back at that episode in lieu of todays topic. Here are the summary notes from 2022:

15m

Mar 03

As the episode comes to an end, the group winds up focusing on the need for better, more frequent MASH education as a pivotal need if we are to flatten the growth curve of the MASLD pandemic. In the process, the discussion returns to the risk for women and the important role they can play.  Louise Campbell starts this conversation by harkening back to the issue of post-menopausal women. As she notes, women provide most of the hands-on care in health system, and also do most of the cooking and food shopping for the home. To Louise, targeting women also targets children, so educating women will have multiple derivative benefits. Zobair Youonossi agrees completely, particularly for the low SDI countries. I suggest that slowing prevalence and disease has two elements: fewer patients at the starting line (or with early MASLD) and better therapies and programs for patients who already live with the disease. I also ask whether the consumer uptake of GLP-1s might have an impact in the US. Zobair states that educating children is the key long-term driver and that the effect of consumer medical behaviors like taking GLP-1s is likely to be minimal. He also believes that MASLD requires more attention from global and national governmental and non-governmental players…NOW! This episode does not have a formal closing question, but the rest of this conversation offers a wrap-up of each panelist’s perspective.

9m

Mar 03

This conversation focuses largely on the work of the Global NASH Council, an effort of over 200 stakeholders in more than 50 countries to address a range of macro issues in the MASLD space. Zobair Younossi, who is the Global NASH Council Chair, starts this conversation by discussing a specific Global NASH Council project on how to implement guidelines for different specialties across regions. He offers two reasons this is such an important project. __ __ Zobair goes on to discuss other Global NASH Council projects, ranging from shared biopsies to the previously mentioned modeling activities. He notes its growth in size and expresses gratitude to the other global MASLD leaders, including Jörn Schattenberg, who are part of one of more of the Councils major projects. Roger Green asks Zobair to put the guidelines project and the Councils policy focus in the context of his earlier comments about high SDI vs. low SDI countries. He describes differences in what food insecurity means between the two types of nations and how that should affect each country’s pursuit of policy and guidelines. He also suggests that it will be more important to provide patient and provider information for specific low SDI countries.

8m

Mar 03

This conversation starts with a focus on slowing the growth of the MASLD pandemic, and then veers slightly into a discussion of the specific issues post-menopausal women face with MASLD.  Roger Green starts by commenting how it seems both pivotally important and highly efficient to find a way to flatten the growth curve, and he asks Zobair what he considers key to doing so.  Zobair replies that the key is to focus on multidisciplinary care centered around primary care, which will require extensive physician education. He also comments that countries may differ widely in what their current MASLD priorities should be. He introduces the idea of the sociodemographic index and the difference between high and low SDI countries. To Zobair, it is critical to elevate the issue of how to support low SDI vs. high SDI countries, which involves, in different ways, every stakeholder from WHO down to patients and their advocates.   Louise Campbell shifts focus to point out that the article raises a point about the increased risk of MASLD to postmenopausal women. This brings up a range of comments, the most important of which revolve around the need to educate OB/GYN physicians and their allied providers on the important liver risk to post-menopausal women.

10m

Mar 03

Initially, this conversation focuses on how cost-effectiveness issues relate to the MASLD Disease Burden. In the process, Zobair Younossi provides education on some of the metrics and concepts pivotal to drug value assessment. Roger Green starts off asking how the economics of treating MASH stack up against hypercholesterolemia at the birth of statins in the 1980s, where the medical benefit was clear but economic was harder to manage. Zobair proceeds to describe the process by which the cost effectiveness of drugs is measured, computation of Quality Adjusted Life Years, or QALYs, and how different countries vary in the level of QALYs they consider cost effective. He also notes that within the US, at least, we may be willing to accept five times greater cost per QALY than for another. He also points out that cost effectiveness grows as new therapeutic options include price competition into a market. Louise Campbell shares the specific US cost numbers from Zobair’s article, which she describes as “frightening,” particularly given the rate of growth in the disease and society’s lack of efficacy in shifting the curve on this. Zobair responds by saying that one goal of the article was to create awareness that regular surveillance of diabetic patients for MASLD could have a significant economic impact in the US.  As the conversation winds down, Jörn Schattenberg comments that all this is a team effort and Zobair agrees heartily.

10m

Mar 03

In this opening conversation on MASLD disease burden, Zobair Younossi summarizes and expands on some key points from the recent Diabetes Spectrum review article he co-authored with Linda Henry. Zobair starts by discussing the recent review article, which he describes as "a summary of a large body of evidence thats being generated." He points to three pivotal issues: __ __ Jörn Schattenberg joins the conversation to commend Zobair on his work, which, as Jörn puts it,  "educate[s] us as physicians on where the risk factors and the at-risk populations are, and were moving that way. I mean, were trying to focus on patients with diabetes that are more advanced from the hepatologist perspective." He also discusses the ongoing effort to educate endocrinologists and primary care about these issues as well, since those two specialties treat the lions share of diabetic patients.  Zobair goes on to describe the Markov models of disease cost his group has built already in seven countries, and plans to build in more. Key point: MASLD is costly everywhere, but the structure of cost and, most importantly, public health solutions will vary from country to country.

11m

Mar 03

Zobair Younossi, Chair of the Global NASL Council, publishes seminal papers  on MASLD epidemology, cost of disease, and related public health needs regularly. Co-hosts Jörn Schattenberg, Louise Campbell, and Roger Green ask questions and share perspectives from their own experiences. 00:00:00 - Surfs Up: Season 5 Episode 4 Opening introduction, including brief quotes taken directly from the episode discussion. 00:02:45 - Introduction and Groundbreaker Panelists swap brief, lighthearted comments about where they are geographically and where they have been recently. In the groundbreaker, each shares one piece of good news from the previous week. 00:11:15 - Epidemiology article Zobair Younossi discusses the recent review article, published earlier this month in . He starts by discussing incidence and growth rates for MASLD, MASH, and cirrhosis across the world, and how these differ by country. He goes on to discuss the impact of MASH on patient Quality of Life and the high correlation between multi-metabolic patients (most notably diabetics) and negative outcomes. 00:15:55 - Panel questions and comments Jörn Schattenberg joins the conversation to praise this and other of Zobairs works for helping physicians know what to do when they decide to become more engaged in treating MASLD and MASH. This leads Zobair to discuss the Markov model they have created to evaluate burden of disease. 00:19:14 - Costliness and cost-effectiveness of therapy In response to a question from Roger Green, Zobair describes the criteria and metrics used to evaluate the cost-effectiveness of a new drug or diagnostic. Louise Campbell comments on how high and underappreciated the social and economic burdens of disease are to every global society. Zobair notes that health economists do not focus on liver disease as a discreet set of costs and burdens. 00:27:17 - Goals and activities for the next few years Roger states that given how fast the  MASLD and MASH populations are growing, an effort to "flatten the curve" would be heroic. Zobair replies that each country needs to fight liver disease, but that each country will have different immediate challenges. 00:31:28 - Womens health and liver health Louise notes that the epidemiology paper refers to the high level of risks among women over 55. This leads to a discussion between Jörn, Zobair and Louise on the higher risk level post-menopausal women experience and some pathological elements that make this important. 00:34:58 - Global NASH Council Zobair bridges this portion of the conversation to discuss the work of the Global NASH Council, a group of >200 members in >50 countries organized into different workstreams to create knowledge and awareness around MASLD and MASH. 00:38:59 - Low SDI and High SDI countries To Zobair, one element in the global effort on MASLD and MASH is the recognition that High SDI (wealthier) and Low SDI (power) countries face dramatic differences in the challenges they face. 00:41:14 - Reducing the rate of disease growth To Louise, educating women might be a key to driving awareness, both because post-menopausal women live at higher risks and because they cook and schedule for their families. This leads to a broader discussion about the most effective education starting with children. Finally, Zobair discusses the importance of making all stakeholders PLUS global agencies recognize the scale of this challenge and to act in concert with increasing urgency. 00:48:42 - Question of the Week The first Question of the Week asks what steps each of us can take to help stem the pandemic. 00:49:41 - Business report News on audience metrics, the first Question of the Week, next weeks episode and this weeks conversation

52m

Feb 29

Our first conversation focusing on the new MASLD nomenclature surfaces as part of our coverage of the EASL Congress 2023. Hepatology researchers and key opinion leaders Sven Francque and Ian Rowe joined Jörn Schattenberg and Roger Green to discuss the value of the new nomenclature and its current and anticipated impact on their practices.  This conversation focuses on the outcome of the nomenclature process, a three-stage Delphi process that produced new names and classifications for what had previously been known as fatty liver disease and henceforth will be known as steatotic liver disease (SLD). Sven, who was actively involved in the entire exercise, gives a concise summary of the process by which the new classifications were developed and how the new terminology will work. The rest of the conversation focuses on three issues. __ __

15m

Feb 27

This conversation ties up several issues related to MASH and the new MASLD nomenclature that the panel did not touch on earlier in the episode. These range from the impact the nomenclature might have on other elements of treatment to the impact of this effort over time. Finally, the panelists grade the process to date (they admit, their views might be a bit biased) and signs of success.  Roger Green starts this conversation by asking what impact panelists believe the new MASLD nomenclature might have on NITs. From one perspective, Meena Bansal notes that it should have no impact given that NAFLD/NASH and MASLD/MASH map so similarly on top of one another. From a different perspective, Jeff Lazarus asks whether the nomenclature and accompanying guidelines from professional societies will result in more testing. The group aligns around the idea that patients living with Type 2 diabetes are an excellent target for increased testing with NITs given the high overlap of the two groups. Maru Rinella comments specifically that all efforts to tie T2DM to MASLD as frequently common metabolic diseases will be helpful and that discussing the proper use of NITs might be one way to make this connection. Louise Campbell agrees that increased focus on "Healthy Livers, Healthy Lives" will drive exactly these kinds of discussions. The rest of the episode consists of Roger asking panelists three questions, to which they respond:  __ __

12m

Feb 27