Surfing the MASH Tsunami

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After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. This conversation speculates where potential bottlenecks in getting drugs to patients might emerge.

Louise points to payers as a significant barrier en route to product adoption. Roger suggests it depends on the healthcare system, but generally agrees with Louise. He references the past development of a Hep C treatment for a comparable example. Payers slowed adoption of drugs with clear long-term benefits due to the short-term cash outlays. Jörn also shares his belief that payers will be the source of bottleneck. He suggests that appropriate patient pathways and stratification provide the best counter-strategy. In response, Louise returns to her point that our health systems are not ready to implement Fatty Liver drug therapy yet, much less over the next 6-12 months.

The conversation then shifts to the more recent theme of a “combo-combo world,” coined by Mazen Noureddin in Season 3, Episode 43. Mazen had introduced the idea that combinations of biomarkers are necessary to diagnose and stage, while combinations of drugs provide optimal therapy. To finish, Jörn discusses the value of the consortia – LITMUS, NIMBLE, NAIL-NIT and Rohit Loomba’s Goldmine – in moving this issue forward.

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After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. This conversation focuses on exciting data they anticipate for multiple different drugs. They also discuss the implications positive drug trials and anticipated approvals will have for NAFLD treatment.

Roger starts by discussing the educational work Intercept was beginning before obeticholic acid received its complete response letter in 2020. He underlines the logic that doctors will be more eager to learn how to treat when given a reliable way to achieve results.

Jörn expresses specific enthusiasm about the future of FGF-21s as implicated by the recent Akero Phase 2b results. Roger then notes the promising data and/or approvals on the horizon for four different modes of action. He suggests that with these, the ideas of combination therapy and disease regression or resolution may become real for the first time. Louise agrees about the promise of the medications. However, she expresses strong concern that the diagnostic and patient management structures will not be in place before the drugs arrive. This shortcoming will slow the ability to bring these benefits to patients. Jörn returns to the excitement about the drugs and the idea that significant amounts of data may come as soon as November’s AASLD meeting. As the conversation ends, the group begins to explore where bottlenecks in getting drugs to patients might exist.

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After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. This conversation explores the role of multiple biomarker tests in the diagnostic process and how these might vary in the panelists’ home countries.

To begin, Louise notes that in the UK, many primary care physicians do not perform even basic liver tests, making it impossible to compute FIB-4. Roger questions whether publicizing of guidelines like the AACE or EASL guidelines will speed uptake of FIB-4. The guidelines recommend that front-line physicians not screen their T2DM patients for NAFLD, since 80+% will test positive. Instead, they recommend using a FIB-4 test to identify patients at risk due to current fibrosis. Roger then asks whether these guidelines will move into actual practice. Louise and Jörn each note that in their countries, front-line professionals are not required to perform liver enzyme blood work. Yet, these tests are pivotal for early liver screening. Louise doubts that change will come until after an expensive drug is approved, at which point there will be economic motivation to test. Jörn is more hopeful that with simple tests, he and other hepatologists can educate endocrinologist colleagues on the reasons to adopt this testing strategy over time.

As the conversation wraps up, Jörn begins to segue from the future of care pathways to the exciting future of drug development.

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After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. This conversation focuses on the need for different specialties to align in treating the complete range of non-communicable metabolic diseases.

Jörn starts the conversation with a personal highlight: he attended last month’s EASD meeting for the first time. Historically, few hepatologists attend this meeting. He views his attendance as indicative of a trend: hepatologists and endocrinologists working together on diabetes and NAFLD. Louise echoes the sentiment that liver health is gaining traction as a critical function of holistic patient management. However, she notes cardiology appears to be slow on the uptake. She also asserts that nurses should have a clear role in this discussion around holistic patient management.

Roger links collaborative energy to a completely different kind of energy formation: capital investment. He notes Akero’s recent filing for $230 million in equity to help bring efruifermin to market based on Phase 2b results. If this effort succeeds, it may signify that the financial markets are becoming more optimistic about NASH drugs after several years of extreme skepticism.

As the conversation winds down, Jörn returns to his original theme to discuss how endocrinologists have received the concept of liver disease as part of multimorbidity management in patients living with T2DM. He reports that the endocrinologists have been eager to learn the liver testing tools and metrics they should use. They require simple tests with high negative predictive values. That way, they know when it is time to send a patient to the hepatologist. This reminds Roger of Quentin Anstee’s talk in Dublin about the different roles that first and second biomarker tests play in the diagnostic process. The conversation finishes with Roger making a correlation between Quentin’s talk and Jörn’s recent experiences engaging with the endocrinology community.

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The last month has witnessed several major Fatty Liver conferences and others that touch on NAFLD in the context of metabolic disease. One common theme has been the need for different specialties to align in treating the complete range of non-communicable metabolic diseases. In this episode, Roger Green, Jörn Schattenberg and Louise Campbell propose factors that have the potential to dramatically shift the force around fatty liver disease over the next six months.

Jörn starts the conversation with a personal example of a larger trend: he attended last month’s EASD meeting for the first time. Historically, few hepatologists attend this meeting, but Jörn believes his attendance is indicative of a trend: hepatologists and endocrinologists working together on diabetes and NAFLD. Louise echoes the sentiment that liver health is gaining traction as a critical function of holistic patient management, although cardiology appears to be slow on the uptake.

Roger links this collaborative energy to a completely different kind of energy formation: capital investment. He notes Akero’s recent filing for $230 million in equity to help bring efruifermin to market based on Phase 2b results. If this effort succeeds, Roger suggests that it may signify that the financial markets are becoming more optimistic about NASH drugs after several years of extreme skepticism.

Next, Jörn returns to his original theme to discuss how endocrinologists have received the concept of liver disease as part of multimorbidity management in patients living with T2DM. He reports that endocrinologists have been enthusiastic about the idea and eager to learn the liver testing tools and metrics they should use.

The group then responds to the AACE guidelines promoted last May. The guidelines recommend that front-line physicians not screen their T2DM patients for NAFLD, since 80+% will test positive. Instead, guidelines recommend using a FIB-4 test to identify patients at risk due to current fibrosis. Roger asks whether these will move into actual practice. Louise and Jörn each state that in their countries, front-line treaters are not required to perform liver enzyme blood work. These tests are pivotal for early liver screening. Louise doubts that change will come until after an expensive drug is approved, at which point there will be economic motivation to test. Jörn is more hopeful that with simple tests, he and other hepatologists can educate endocrinologist colleagues on the reasons to adopt this testing strategy over time.

The conversation shifts to speculation as to whether prescribers or payers will be the source of bottleneck in patient care pathways at the outset of a drug approval. The group generally agrees that pushback will come from the payers and that healthcare systems are not yet ready. They then look towards the social and political will to take action on the crisis. In response to Roger’s question, the group acknowledges the immense hurdles present in changing provider behavior over the next 6-12 months while stressing the importance of provider education and patient empowerment.

Finally, the group discusses the future of the recently coined “combo-combo world,” where correct diagnosis will require a combination of biomarker tests and treatment may require a combination of therapies. At the end, Roger asks what changes each member envisions. Surf on to find out.

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The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. In Season 3, Episode 46, program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Roger Green on-site from Dublin to review their reactions immediately after the conference ended. The panelists note the impact of weight change and lifestyle modification in clinical trials while utilizing insights from the bariatric and diabetes fields.

In this episode From the Vault, Roger Green, Stephen Harrison, Ali Aminian and Wayne Eskridge discuss how weight loss and GLP-1s or Double/Triple Agonists in relation to SPLENDOR. This conversation comes from Season 2, Episode 61.3.

Season 3, Episode 46 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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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 final conversation 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.

Send us Fan Mail

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 Roger Green on-site from Dublin to review their reactions immediately after the conference ended. In this conversation, the panelists examine the impact of weight change and lifestyle modification in clinical trials while utilizing insights from the bariatric and diabetes fields.

This conversation continues the issue of Hawthorne effects in trial design. Hannes starts by noting we can learn from obesity trials – and also from TV shows like “Biggest Loser” – that people regain weight without continued support. Roger shares a thought he believes might have come from absent co-host Louise Campbell, recalling the immediate impact FibroScan has on illustrating results and influencing patient motivation. Sven notes that the issue of lifestyle management in a NASH trial has been a significant issue for the Liver Forum and other supportive groups in terms of trial design and also the power calculations that shape trial size. Mazen closes the discussion by stating that recent meta-analyses show that placebo rates tend to run around 20% and that this might be the right placebo result for power calculations. As the conversation winds down, he shares his guiding principle for these issues: “Prepare for the worst and hope for the best.”

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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The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. In this conversation, the panelists explore issues around clinical trial design, focusing specifically on the value of Phases 2a and 2b and whether improvement in patient self-management during trials is a research artifact or a replication of reality.

This conversation addresses two issues in clinical trial design. First, Roger Green draws on the Session 9 discussion of failed trials to ask which is the right way to proceed when a drug in a Phase 2b trial fails to reach its primary endpoint but a subanalysis reveals a second possible path to Phase 3. He notes that this was the case with elafibranor, one of the Session 9 case studies, as well as obeticholic acid, a drug whose Phase 3 trials met its efficacy endpoints but is not yet approved due to regulators’ seeming perception that it lacks an acceptable cost:benefit ratio. The group points to reasons these may have been solid decisions before noting that the market and scientific community both expect higher performance from drugs today than they did several years ago. Mazen Noureddin asks whether exceptionally promising drugs might consider moving directly from Phase 1b to Phase 3; the group agrees that Phases 2a and 2b will have value for virtually every drug at this time. 

The final question comes from Roger, who asks whether improvements in patients’ diet and lifestyle during the clinical trial constitute a “Hawthorne effect,” as some stated on Saturday morning. He notes that in the literature, a Hawthorne effect is a change that might affect clinical trial results but will have no meaning in day-to-day practice. By that standard, improvements in patients’ diets and lifestyles do not constitute a Hawthorne effect since we want to effect these behaviors in all patients. Mazen Nouredin disagrees, noting that after trials, patients’ behaviors tend to revert to pre-trial levels, thus making improved behavior a confounding factor in analyzing trial results. The group comes to no clear consensus on this issue.

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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The 2022 NAFLD Summit uniquely 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. 

At the outset of this episode, the group discusses the benefits of participating in a smaller conference more focused on the challenges presented by the field of NAFLD. Mazen likens the NAFLD Summit to NASH-TAG, asserting that these specific conferences advance the field and address deeper layers around the issues that matter most.

Mazen goes on to raise the issue of glycemic control and the impact of glycemic control on NASH drug performance. This bleeds into a brief point about the value of simply stopping fibrosis progression instead of the need to prove regression. He then identifies two sessions he considered particularly valuable: the Saturday morning autopsy of failed Phase 3 trials and therapeutic discussion about drugs at different stages in development. This segues into a discussion of optimism derived from the recent Akero and Altimmune results. In terms of Altimmune, Mazen asks whether the drug should go directly from Phase 1b to Phase 3. The panel generally believes that Phases 2a and 2b have value for virtually all development drugs. Further, the panel agrees that the presentations on three failed Phase 3 trials were richly valuable and that each offered its own clear lessons for researchers.

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.