Surfing the MASH Tsunami

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Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. To reflect on the insight-laden occasion, Stephen Harrison and Jörn Schattenberg join Roger Green to explore emerging drug development stories in detail.

In this session, conversation shifts from resmetirom to Mazen Noureddin's "NASH Monopoly" game and focus on the value of FGF-21s and glucagon agents. Stephen posits two comments about GLP-1s. First, there is now adequate data suggesting that GLP-1s will not melt away all liver fat and as a result lead to dramatic fibrosis regression. Second, we know from a small sub-cohort of patients in Akero's SYMMETRY trial that patients already on fairly low doses of GLP-1s saw what Stephen describes as an 'incredible' and incremental benefit for the FGF-21 agent, efruxifermin. The group notes that while glucagon dual and treble agents are likely to produce dramatically more robust results in weight loss and liver defatting than GLP-1s alone, they still seem unlikely to 'usurp the need for other types of agents.' From here discussion considers the FGF-21 class. Stephen notes that two drugs, efruxifermin and pegozafermin, have demonstrated significant efficacy against fibrosis. As the conversation concludes, the panelists agree that earlier, more aggressive screening to arrest cirrhosis will become pivotal and will not occur until the right drug becomes available. 

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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Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. To reflect on the insight-laden occasion, Stephen Harrison and Jörn Schattenberg join Roger Green to explore emerging drug development stories in detail.

This conversation continues on data presented by Stephen on the MAESTRO series of trials for resmetirom. It starts with a few clarifications on data presented in regards to liver volume. This discussion point evolves to consider how liver volume is not well understood and the three speculate what sort of useful insights can be derived from bridging that gap in knowledge. Stephen steers discussion back to the specific data by discussing the resmetirom safety profile. First, he shares the practical implications of safety for these drugs in everyday use. Next he provides an encouraging safety profile for the trial. As he does so, he shares thoughts about how to and how not to interpret a diahrea metric. Jörn responds by stating that the safety and liver volume profile suggest a reduction in liver pain and associated improvements to quality of life. He suggests the latter might be important with European regulators. As the conversation winds down, Stephen expresses his hope that the rolling submission with possible priority review and this profile will produce extremely positive news within the next 6 to 8 months.

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].

Stay Safe and Surf On!

Send us Fan Mail

Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. To reflect on the insight-laden occasion, Stephen Harrison and Jörn Schattenberg join Roger Green to explore emerging drug development stories in detail.

This conversation focuses largely on therapeutic candidate, resmetirom, and a series of MAESTRO-NASH trials that will hopefully lead to a first drug approval and treatment for NASH. Stephen, lead Principal Investigator of the MAESTRO program, begins by outlining the resmetirom clinical trial package in its entirety. Before Stephen shares numbers from the trial, Jörn opens a discussion around efficacy endpoints. He notes the structure of reading biopsy and suggests that reporting improvement in fibrosis and NASH resolution might not accurately reflect the extent of efficacy once the MAESTRO outcomes trial completes several years from now and patients are treated in practice. Stephen goes on to share the efficacy outcomes of the MAESTRO-NASH trial and offers notes from several different perspectives around dosing, placebo, metrics and other elements of the study population. Finally, Stephen suggests where in the liver he believes the drug works and why the drug might have more robust effects than can currently be measured using the testing tools available.

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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Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. For this feature, Stephen Harrison and Jörn Schattenberg discuss at depth drug development insights emerging from the meetings with host Roger Green.

As lead Principle Investigator, Stephen expounds on Phase 3 MAESTRO-NASH data on resmetirom that he presented during the opening general session. He begins with a cogent backdrop of the study parameters, including endpoint criteria, before detailing results and implications. In his analysis, Stephen notes the challenges of teasing how well a drug performs in comparison to placebo. He then expands on the power of AI in digital pathology and its ability to enhance assessment of biopsy beyond ordinal scoring systems. Jörn adds that these extension studies are fascinating for their ability to hone in on patient benefits experienced beyond liver histology alone. From here, the group discusses at length deepening the field's understanding of liver volume reduction.

Moving on, Roger revisits a metaphor from Mazen Noureddin in last week's episode which likened the two most valuable properties in "NASH Monopoly" to GLP-1s and FGF-21s. Stephen suggests a takeaway to be that "GLP's are coming to the forefront as a very active player in the fields of obesity, diabetes and ultimately CV risk reduction." The group next agrees that, in Jörn's paraphrased words, while a defatting effect on the liver can be beneficial, treating obesity by itself does not outright resolve fibrogenic burden and there remains the need for more liver-directed drugs. Stephen expands on his recurring phrase of "not all FGF-21s are created equal" while transitioning the group's focus to consider the fact that an increasing number of patients are progressing to cirrhosis. The remainder of the conversation posits fascinating and far-reaching speculations on the future study of disease including revolutionizing the way we diagnose HCC. In final comments, each panelist touches on one additional element in the drug development landscape to emerge out of an exciting month of June. 

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].

Stay Safe and Surf On!

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Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.

This final conversation between Roger and Jörn begins by moving beyond the subject of drugs to the importance behind noninvasive testing and the myriad ways by which the term artificial intelligence is being claimed. Jörn talks about a poster he shared at EASL around an AI-assisted mode called qVessel which investigates the ability of researchers to quantitate changes in blood vessels and liver architecture as fibrosis progresses. This example provides contrast between how we develop diagnostic scientific insight versus drug approval process versus clinical applications and patient treatment. The conversation continues on to highlight some of what Jörn and Roger consider to be some of the most exciting drug development pieces to emerge from the EASL and ADA meetings. This leads to comments around how the nature of the questions being asking in 2023 versus 2019 demonstrates how much the field has learned about liver disease over the last few years. Our entire key opinion leader and advocate team has been struck forcibly by how many studies in the last month provided significant advances in knowledge and how some of these advances may change an underlying appreciation of drugs, diagnostics, artificial intelligence, machine learning and how we think about Fatty Liver disease overall.

Both conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). Stay tuned for more in the subsequent conversations to be released. If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, 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

Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.

This first conversation with Jörn starts with discussion around the idea that even dramatic improvements in obesity medications will not resolve all issues related to fibrosis in MASLD patients. After speculation around the therapeutic landscape for NASH, conversation turns toward the new nomenclature consensus and what this will mean for the liver community and beyond.

Both conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). Stay tuned for more in the subsequent conversations to be released. If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, 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

Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.

This second and final conversation with Mazen continues to explore what we do or do not know about the different mechanisms of action in NASH drugs and the commercial implications. Later, the Monopoly metaphor around NASH therapeutic development as described in the preceding conversation is expanded. Roger shares his interesting idea on how Big Pharma is similar to the role of Hollywood in movie production and distribution opportunities. Finally, the two discuss why it is critical to move beyond ordinal histopathology reads in the drug approval process before sharing final thoughts around what factors are contributing to an exciting future for combating liver disease.

Both conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). Stay tuned for more in the subsequent conversations to be released. If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, 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

Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.

This first conversation with Mazen begins with comments on the many excellent drug development studies emerging from both EASL Congress and the ADA's Scientific Sessions meeting. While the two share exceptional results, they also explore potential downsides in terms of tolerability and longterm antibody inflammation. An illustrative new metaphor is coined by Mazen in which the NASH therapeutic landscape is likened to the game Monopoly. In "NASH Monopoly," each street or monopoly presents a mechanisms of action. The two most expensive streets to GLP-1s and FGF-21s. He goes on to commend and describe the promise of GLP-1s and the double and triple agents in development as leading to such significant weight loss that some question the need for bariatric procedures altogether.

Both conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). Stay tuned for more in the subsequent conversations to be released. If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, 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

Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego.   

This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.

The first conversation with Mazen begins with an illustrative new metaphor in which the NASH therapeutic landscape is likened to the game Monopoly. In "NASH Monopoly," each street or monopoly presents a mechanisms of action. The two most expensive streets to GLP-1s and FGF-21s. He goes on to commend and describe the promise of GLP-1s and the double and triple agents in development as leading to such significant weight loss that some question the need for bariatric procedures altogether. The conversation also covers some issues around non-invasive testing, nomenclature changes and how emerging drug classes will increase options -- and complexity -- for prescribers.

The second conversation includes two of the podcast's co-hosts, Jörn and Roger. For the most part, the focus stays on drug development issues. Jörn's first note underscores growing points of intersection between different fields concerned with managing metabolic dysfunction and how different toolkits might have positive impact on liver health. Roger switches the metaphor of Monopoly to a new description of the developing therapeutic landscape akin to a desert where mirages present as promising drugs and "any drink of water is as good as any other drink." As conversation continues, Jörn and Roger expound on the subject of new nomenclature and what this will mean for different stakeholders.

The two conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, 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!

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Surfing NASH delivered a second wrap-up session on-site in Vienna as a part of its real-time coverage of a truly thought-provoking EASL Congress 2023. This conversation held after the Saturday late breakers features key opinion leaders Hannes Hagström and Michelle Long, entrepreneur and epigenetics advocate Rachel Zayas and patient advocates Jeff McIntyre and Michael Betel alongside host Roger Green.

This conversation covers a few interesting moments from the conference, starting with the appearance of Tetiana Deshko to speak about the gruesome realities of public health care in Ukraine during the invasion. From there, Jeff talks about a broader issue of how we support funding of treatments in parts of the world that lack hepatologists or adequate resources. The group also discusses the idea that Predictive Health Intelligence in the UK has begun to improve patient screening dramatically with a simple, non AI-based data analysis methodology that could likely be applied in a variety of regions. Michael comments on the session where the question arose whether physicians should inform patients about having fatty liver disease before drug therapies were available to treat it. Spoiler alert: the patient advocate answer is an emphatic yes! Finally, Roger's closing question asks the group about what they learned in the meeting that will change their work going forward.

For a variety of reasons, EASL Congress 2023 has been looked forward to by the liver community with arguably an unprecedented sense of excitement and intensity. The conversations resulting from the podcast’s two real-time reviews suggest that the actual event met or exceeded such high expectations. If you have any question or interests around EASL Congress, 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!