Surfing the MASH Tsunami

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The wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.

This conversation starts with continued focus around the new nomenclature, but moves on quickly from there to Louise's highlight of the year. She talks about how patients now play a larger role in all facets of education and drug development. Jörn agrees with this note and suggests that the level of patient involvement in this disease is far greater than what is observed elsewhere. Roger agrees with both statements, although expresses caveats about the need over time to move forward from simply including patient voices to actually listening to what they have to say and taking guidance from them with higher degree of success. From here, Roger introduces his highlight which is a combination of NIT development that will make these tests more pivotal on patient diagnosis management and, separately, new artificial intelligence modalities that utilize biopsy results to produce better pictures and a far more sophisticated level of disease understanding than we've had to date. Jörn and Louise both comment on issues they consider pivotal and highly valuable in terms of the use of NITs and lessons from AI.

Reviewing this episode and the various conversations is a strong reminder of how much information has already become available this year and what it portends in terms of future episodes and an ever-increasing explosion of new information about liver disease, drugs, testing, and so much more. If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, 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 wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.

This conversation focuses significant attention on issues related to the change in nomenclature that was rolled out in final form at the recent EASL Congress in June. It starts with Roger sharing an item from a recent news story about Madrigal Pharmaceuticals deciding not to engage in the nomenclature change until regulatory agencies ruled on it - a logical step given where resmetirom stands in the approval process. Roger comments that while the name change is necessary, there are some challenges in terms of communicating the disease. Louise notes how important communicating disease properly is in educating patients and expresses concern that professionals might not communicate the disease (or communicate it properly) if there is confusion around nomenclature as there currently appears to be. Jörn asserts that we're not confused about the disease that patients have, but only how to describe it. Roger suggests that while he is not concerned about hepatologists communicating new nomenclature, he does have concerns around the ease and clarity by which primary care and nursing professionals who populate the frontline will be prepared to deliver this new information. Jörn and Louise agree with this take and Jörn states that we need to shift focus towards looking at how to educate the frontline treat categories if we are to succeed with this nomenclature and the work that needs to be done for this disease.

Reviewing this episode and the various conversations is a strong reminder of how much information has already become available this year and what it portends in terms of future episodes and an ever-increasing explosion of new information about liver disease, drugs, testing, and so much more. If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, 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 wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.

This conversation begins with Louise detailing a paper that she recently co-authored on 'The Accuracy of Ultrasound Controlled Attenuation Parameter (CAP) in Diagnosing Hepatic Fat Content.' The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy. Notes on the topic broaden to consider the value of elastography and the challenges of making proper use of it. From here, the group shares comments around how the major events and conferences have panned out so far for 2023. Jörn notes that while the volume of information available grows over time, a clear set of events which captures attention relates to the advancement of resmetirom as a potential first approval for NASH-directed therapy. He recounts the trajectory of this story beginning in December 2022 with a press release of positive Phase 3 topline results, to follow up data presented at EASL Congress 2023 in June. Jörn highlights his excitement for analyzing these results on the podcast with Stephen Harrison, Principle Investigator of the MAESTRO studies. Briefly, Jörn underscores the second key event of the year: new nomenclature for liver diseases. When his comments around this conclude, the trio spend the rest of this conversation discussing the importance behind a resmetirom approval and some of the interesting data that emerged from later releases of the MAESTRO trials.

Reviewing this episode and the various conversations is a strong reminder of how much information has already become available this year and what it portends in terms of future episodes and an ever-increasing explosion of new information about liver disease, drugs, testing, and so much more. If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, 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 episode From the Vault looks back to the podcast's first episode dedicated entirely to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Surfing alongside this rich discussion are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green.

Roger begins this conversation by stating that everyone eventually makes poor dietary choices. The group agrees through various examples that the key is to not let a momentary shortcoming deter progress along the wellness journey. Shira emphasizes that relapse is part of the process and ought to be factored into patients’ long-term plans. She goes on to disclose her love for chocolate and how patients can still have some of their favorite foods in their new diet. This leads Ken to describe diet as simply one aspect of a full-life balancing act. For him, perfectionism is the enemy. The group goes on to consider the psychology of decision making around diet in similar terms to that of addiction treatment. Louise notes that while the field of NAFLD deals with areas requiring immense psychological support, those resources are lacking for patients. In addition to including a dietician on the team, she adds emphasis to the benefit of cross-training physicians with education on mental health support. Ken agrees and comments that the US insurance system makes it hard for patients to get the collateral support they need.

If you have questions, comments or interests around this subject, 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 wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.

Louise starts by detailing a paper that she recently co-authored on 'The Accuracy of Ultrasound Controlled Attenuation Parameter (CAP) in Diagnosing Hepatic Fat Content.' The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy. From here, Jörn shares his take on the biggest stories of the year thus far. He begins by recounting the December 2022 press release of positive Phase 3 topline results for resmetirom and describes how the data was presented at EASL Congress 2023. Jörn highlights his excitement for analyzing these results on the podcast with Stephen Harrison, Principle Investigator of the MAESTRO studies. Secondly, Jörn underscores the adoption of new nomenclature as an obvious hallmark of the year.

Roger notes several developments in the resmetirom story following the EASL presentation, namely around a submission to FDA and potential timeline for approval. Louise suggests that, "from the patient advocacy perspective, there has to be something approved shortly to prove that the path that the FDA has set is actually achievable." The group also explores the importance behind having quality of life measures as opposed to solely targeting histological improvement of fibrosis. These ideas lead Roger to register his interest in developing understanding around the role of inflammation which has been explored more recently on the podcast.

The conversation shifts to consider the new nomenclature and what activities are required in its successful implementation. Several important ideas emerge around education and moving forward collectively in continued pursuit of promoting liver health and saving lives. Jörn summarizes that fundamentally the patients and the disease remain the same and that there is actionable knowledge around how to prevent, diagnose and treat. As the session winds down, the trio focus on providing a glimpse into what's coming up for the SurfingNASH program. Listen on to learn more about what you can expect to hear from the Surfers!

If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, 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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Last year, Stephen Harrison expounded on a string of press releases presaging some of the most promising data of the last decade in NASH drug development. As Principal Investigator, he reviewed on the podcast Phase 2b results from Akero’s HARMONY Trial. This is a 24-week study evaluating the efficacy and safety of the FGF-21 agonist efruxifermin (EFX) in patients with clinically relevant NASH (F2-F3). The study met its primary endpoint for both the 50mg and 28mg EFX dose groups. Respectively, 41% and 39% of EFX-treated patients experienced at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24 (compared with 20% for the placebo arm).

Stephen walks through his presentation on Akero’s lead product candidate EFX and two important points emerge. First, Stephen and Sven Francque share the idea that “not all FGF-21’s are created equal.” FGF-21’s themselves need to be stabilized due to their two-hour half-lives. The first FGF-21, pegbelfermin, was PEGylated and revealed significant challenges in clinical development. EFX is a bivalent structure – two molecules stabilized by a fusion protein. This appears to work far better. The conversation continues with more points and questions about the study results and implications. An interesting idea surfaces: EFX might function better as an induction therapy to be followed by an oral maintenance therapy and a long-term monotherapeutic solution. As the session winds down, the group speculate the dynamics of what happens when disease regresses to a point where there is far less liver damage.

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This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.

This final conversation covers a range of topics. Jörn starts off with comments around the importance of safety as well as some thoughts about dosing strategy relative to safety and initial tolerability. Stephen picks up on this issue before moving on to consider whether the drugs discussed have an impact on cravings for alcohol and might be successful in a broader set of patients. He then goes on to identify two concerns for the agent class: suicidal ideation and possible amounts of lean muscle loss, both of which need to be for further. Jörn notes that lean muscle loss might be particularly critical in the study of patients with cirrhosis who are frail to begin with. Stephen continues by discussing a review of the frequency of lean muscle loss for GLP-1s, suggesting a 20 to 50% loss in many cases. Finally, Louise comments on the possible psychological effects of this weight loss. All this leads to Roger's final question which asks what have we learned in the last month that might affect research or conceptual thinking going forward? The topics each panelists chooses vary largely, but the concepts and all the thoughts around them are stimulating and worth a listen.

Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence. If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On

Send us Fan Mail

This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.

This episode starts with a welcome (and happy birthday) to Roger as he belatedly joins the discussion. From here Mazen discusses some of the implications of the anticipated upcoming approval for resmetirom and what that will mean for treatment, drug development and noninvasive tests. Stephen nexts dives into the phase 2b pemvidutide trial in greater detail. In response, Jörn notes that the weight loss is not what you might have expected from a GLP-1 and asks whether this has to be a function of GLP-1 to glucagon ratio. Stephen notes that there is a relatively high level of glucagon to GLP-1 in pemvidutide that might translate not only into greater antifibrotic activity, but also possibly a lower level of side effects relative to a combination agent with a lower level of glucagon compared to GLP-1.  

Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence. If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On

Send us Fan Mail

This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.

Mazen starts this conversation by stressing the importance of omics, particularly metabolomics and proteomics, in creating a single blood-based measure that can offer standardization around evaluation or, otherwise, a small set of standard tests. He goes on to describe breakthrough obesity presentations at the ADA meeting and returns to the question that he raised in Episode 31: do we need NASH drugs given how powerful the upcoming weight-loss pharmacotherapies will be? He simply says, yes we do, and describes why. Stephen returns to the topic of omics, stating his preference for additional omics works, albeit with some skepticism about proteomics. That said, he questions whether omics will get a far enough and expresses hope that epigenetics might get even further. The rest of this conversation entails Mazen, Stephen and Jörn discussing biomarkers and omics issues. Stephen wraps up the session by noting that we will have plenty to talk about in this arena for years to come. Finally, he mentions AI as another key area for future growth.

Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence. If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On

Send us Fan Mail

This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.

Jörn and Mazen begin by prompting Stephen with questions around the FASCINATE-2 study outlined in the previous conversation. Stephen confirms that the data presented was based on a planned interim analysis of a prespecified subset of patients at week 26 of a 52-week trial. Mazen next asks questions designed to challenge Stephen to reveal how excited he truly is about the drug (denifanstat) and surrounding data. Specifically, Mazen asks whether denifanstat feels like an add-on agent when compared to more 'mainstream' FGF-21 agents. Stephen responds by referring to a need for what he characterizes as a plethora of agents before commenting on possible and practical differences between orals and injectables. He suggests that injectables seem to produce faster drops in liver fat reduction and ALT improvements than orals, although orals may 'catch up' over time in a sort of 'tortoise and the hare' phenomenon. From here Stephen describes the ways which he might use injectables first in more severe patients before introducing orals after achieving the desired effect. He also talks about simply starting with orals in less severe patients. The group digs deeper into these ideas by introducing ACC inhibitors and pan-PPAR agonist, lanifibranor, to the conversation. Finally, concluding comments return to the theme that injectables might produce stronger efficacy results, although there are several agents yet to be clearly differentiated among orals.

Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence. If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On