Surfing the MASH Tsunami

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Stephen Harrison joins Louise Campbell and Roger Green for an insight-laden episode about challenges and opportunities in NASH drug development. This conversation continues from the preceding discussion on screen fail rates. Louise starts by asking what would the ideal patient look like for an attempt at lowering screen fail rates. Stephen responds with two assertions. The first suggestion is that higher hemoglobin A1C is indicative of disease activity in the fibrosis needed to qualify. Second, Stephen identifies utility in retrieving a FibroScan-AST score as a promising prescreen strategy. From here the conversation considers the variability of liver biopsy and whether there is a convincing impetus for establishing guidelines on the biopsy reading process. As the session winds down, Roger raises the idea that hepatocellular ballooning should be considered as a continuous variable. This proposition primes the following and final conversation to dive deep into the science and art of pathology reading.

If you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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Stephen Harrison joins Louise Campbell and Roger Green for an insight-laden episode about challenges and opportunities in NASH drug development. This conversation breaks away from commentary around the FDA ADCOM meeting on obeticholic acid after Louise begins with a synopsis of the meeting outcome and her general agreement with the preceding conversation’s analysis. From there Roger shifts focus to a powerhouse paper produced by Stephen (and co-authored by friends of the podcast Alina Allen, Julie Dubourg, Mazen Noureddin and Naim Alkhouri) which was published in Nature Medicine earlier in March 2023. When asked what would be the one or two sentences that could best capture it, Stephen simply suggests the title says it all. “There are tremendous amounts of challenges we're faced with in drug development, but those are equally matched by opportunities.” He goes on to tease that the upcoming EASL Congress in Vienna will provide a venue to unpack pioneering insights which will inform new directions in a rapidly moving field. Specifically, Stephen points to interest in what’s emerging from AI-assisted digital pathology. He underscores the role of AI-assisted digital pathology to be pivotal in ushering in a new generation of NITs.  “We need to fully understand how effective our noninvasive tests are in… diagnosis monitoring, response to therapy, predicting outcomes and predicting the magnitude of effect change that links not to biopsy but to an outcome measure.”

On the back end of this session, Roger asks whether there is a specific subject or sector that will catalyze our understanding and management of patients with Fatty Liver. Stephen immediately points to the diabetic population as a set of patients that are going to allow the field to advance quicker. He reasons that endocrinologists are also working intently to better understand and solve this issue. The remainder of the conversation transitions to the topic of screen fail rates.

If you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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Stephen Harrison joins Louise Campbell and Roger Green for an insight-laden episode about challenges and opportunities in NASH drug development. This first conversation begins with an update from Stephen on what he has been working on since last appearing on the podcast. He notes new and exciting data emerging from NGM on aldafermin, an FGF19, which indicates that multiple different mechanisms are demonstrating a positive impact on cirrhosis. Stephen shares that he is “becoming more convinced that we can move the needle in this toughest to treat patient population, albeit prior to them developing decompensating disease. There is hope that this population is not too far gone and we can be impactful.”

From here he goes on to offer an impression on the outcome of FDA’s ADCOM meeting for obeticholic acid as a treatment for pre-cirrhotic fibrosis due to NASH. Among other takeaways, Stephen emphasizes the FDA’s prioritization of safety. If there are safety concerns, there is a need for mitigation strategies to de-risk those concerns. His second point is that statistical significance on a surrogate endpoint does not guarantee conditional approval from the FDA. “The therapeutic index of a drug needs to be such that you're providing a benefit in not having a potential adverse event profile that's similar, if not even higher.” In other words, is the juice worth the squeeze?  Stephen suggests that this first drug really has to set the right tone in terms of user friendliness. The ability to readily be adopted by frontline prescribers outside of the hepatology specialty is critical. As a final thought on the subject, Stephen states the appeal behind pleiotropic drugs that can attack multiple different organ systems with a single pill or injection. 

If you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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This week on Surfing NASH, Stephen Harrison speaks with Louise Campbell and Roger Green about challenges and opportunities in NASH drug development. The conversation comes aptly after the outcome of FDA’s ADCOM meeting for obeticholic acid (OCA) as a treatment for pre-cirrhotic fibrosis due to NASH. The group considers and comments on the safety profile of OCA and what the FDA requires in a first drug approval. However, this session extends much farther to offer a positively stimulating deep dive into the ongoing developments of a range of other therapeutic candidates and research directions for Fatty Liver disease. From the outset, Stephen shares that he is more convinced that we can move the needle in the toughest to treat patient populations prior to them developing decompensating disease. “There is hope that this population is not too far gone and we can be impactful.” Listen on to discover just what is so convincing in this space and what are the elements that give the group hope for the future of Fatty Liver disease.

00:00 Introduction

04:26 What has Stephen been working on since last being on the podcast?

06:21 Stephen's take on the outcome of the FDA ADCOM meeting on OCA for NASH

12:52 Discussing drugs with strong metabolic foundations

16:29 2023 Nature article on challenges and opportunities in NASH drug development

21:40 Disease progression in the diabetic population and screen fail rates

32:17 Deeper dive into histopathology

36:55 Closing question on the future of clinical trial design

If you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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On Friday May 19, 2023, an Advisory Committee for the FDA convened to discuss the benefits and risks of obeticholic acid (OCA) 25 mg for treatment of non-alcoholic steatohepatitis (NASH) with fibrosis. As reported in a press release from Intercept Pharmaceuticals, twelve of 16 voting-eligible members of the ADCOM voted “no” (with two abstentions) on the voting question, “given the available efficacy and safety data, do the benefits of OCA 25 mg outweigh the risks in NASH patients with stage 2 or 3 fibrosis?” Fifteen of 16 voting-eligible members (with no abstentions) voted to “defer approval until clinical outcome data from trial 747-303 are submitted and reviewed, at which time the traditional approval pathway could be considered.”

In this episode, Founder and CEO of the Global Liver Institute, Donna Cryer, joins Surfers Jörn Schattenberg and Roger Green for a session which draws from raw reflections on the FDA ADCOM meeting and its outcome for OCA. The reactions and discussion that unfold are both sobering and constructive as the group reckons with the unfavorable results and the way forward for the liver community. Critically, the group agrees on the idea that this event simply should not be dubbed “another NASH drug goes down.” Rather, the focus remains on the Committee message that goes, “If a drug under this definition of efficacy has a safety profile where we can trust doctors to be able to manage it, we’ll go with it because we understand the patient needs.” Listen on for the full analysis and stay tuned as Surfing NASH continues its coverage in subsequent episodes this week with different KOLs and stakeholders.

If you enjoy the episode, have questions or interest around the outcome of the FDA ADCOM meeting and OCA, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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Surfing NASH offers an exciting preview of EASL Congress 2023 with new guest and EASL Vice-Secretary, Aleksander Krag, alongside EASL Educational Councillor, Sven Francque, and Surfers Jörn Schattenberg, Louise Campbell and Roger Green. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease.

This conversation begins with Jörn describing his anticipations for the meeting where he will be Chair of two separate sessions. One such session of interest will be in the context of a Meet the Experts panel on lean NASH. He also goes on to note excitement for late breakers and learning about novel compounds and newly emerging Phase 3 results. In summary, Jörn describes EASL Congress as “the place where we really shape the future of NAFLD therapy.”

From here Louise highlights her interest in virtually viewing sessions on patients and advocacy and nurses and allied health. Aleksander notes an emphasis in this year’s agenda on having interactive, hands-on elements to participate with. For example, there will be educational opportunities to engage the community with learning how to administer FibroScan. Roger notes the EASL Studio as a capturing component to look out for this year. There will be two studios: one around new treatments, pathways and drug development, and the other dedicated to nomenclature. Roger goes on to describe his personal interest in discovering the latest directions of drug development and noninvasive testing. As the session winds down, Aleksander delivers a comprehensive and compelling list of important activities to be on the lookout for. Surf on to discover what they are.

If you enjoy the episode, have questions or interest around EASL Congress 2023 and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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Surfing NASH offers an exciting preview of EASL Congress 2023 with new guest and EASL Vice-Secretary, Aleksander Krag, alongside EASL Educational Councillor, Sven Francque, and Surfers Jörn Schattenberg, Louise Campbell and Roger Green. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease. In this lively session, the group covers the following topics and more:

00:00 Introduction and meeting Aleksander Krag

10:22 Sharing first impressions and anticipations around EASL Congress 2023

21:09 Discussing educational opportunities

23:10 Comparing in-person and virtual attendance experiences

24:46 Lists of 3 things "you can't miss" for different participating groups

27:30 On building the program

29:57 Scientifically stimulating sessions

31:47  Integrating allied health

34:43 The value of posters and engaging students

36:35 Why should anyone attend virtually?

45:04 What will make this meeting special in the end?


Listen to the full feature for the most detailed preview of the event and follow along as the Surfers convene for live coverage. If you enjoy the episode, have questions or interest around EASL Congress 2023 and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. Program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Surfer, Roger Green, on site from Dublin to review their reactions immediately after the conference ended.

This conversation From the Vault begins with Roger calling attention to a debate around NITs that took place on the opening day of the meeting. Mazen revisits what he has described on this podcast as the coming “combo-combo” world. The group generally agrees that biomarkers in primary care ought to be simple, cost effective and accessible. However, Sven utters a word of caution: while acknowledging the positive potential of NITs, it is still important to evaluate its limitations.

The episode concludes with a round of final reflections. Roger asks for panelists to forecast the most important thing that will have changed between now and when we return for the NAFLD Summit 2023. Surf on to find out what the panel predicts.

This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.

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Donna Cryer joins Jörn Schattenberg, Louise Campbell and Roger Green for an impactful episode which weighs the complexities of competing needs across all Fatty Liver stakeholders. The session expands discourse on the recently discussed ICER draft report to consider a developing landscape around nomenclature consensus and other important and impending decisions. Critically, the group grapples with challenges associated with honoring the precedence of patient-centricity.

This final conversation begins with Roger’s note that while patient stories are driven with emotion and impact, the actual patient journey through diagnosis to treatment can unfortunately be a mechanistic and confusing process. With this in mind, Roger asks how do we bring a more holistic sense of what it means to be a patient or patient advocate to all of these issues discussed as they continue to amplify in a bigger, broader way. Donna’s moving response and the various final thoughts from the other panelists encapsulates the need for patients to be respected for the professional skills they possess which can contribute real impact on how the field moves forward in a stronger, more multi-disciplinary fashion. Listen to the full segment to hear the moving statements.

If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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Donna Cryer joins Jörn Schattenberg, Louise Campbell and Roger Green for an impactful episode which weighs the complexities of competing needs across all Fatty Liver stakeholders. The session expands discourse on the recently discussed ICER draft report to consider a developing landscape around nomenclature consensus and other important and impending decisions. Critically, the group grapples with challenges associated with honoring the precedence of patient-centricity.

Donna opens this conversation with several calls to action for patient advocacy in the NASH community. Her first recommendation is to recruit different disciplines to administer and evaluate an impact report regarding nomenclature consensus. Next, and more broadly, she asks all stakeholders to consider how to genuinely and effectively build an inclusive advocacy community. Roger asks Jörn what he believes to be realistic that the field can do for these aims today. First, Jörn notes that many different societies can agree on what is considered to be a severe patient and what an unfavorable outcome is in terms of liver disease. He goes on to say that with therapies in the pipeline and tests like FIB-4 available and widely implementable now, we have indeed come a long way as a field. The risks he perceives with topics such as the ICER draft report and nomenclature consensus revolve around slowing, detouring or dismantling the tremendous progress that has been made. As the session wraps up, Donna offers her thoughts on where this is all heading. 

Listen to the full feature to engage with these impactful moments. If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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