efruxifermin

Jörn Schattenberg joins the Surfers to discuss drug development in cirrhosis, which evolves into a discussion about how to drive NITs forward.

Historically, NASH drug development strategy has started in advanced fibrosis with the goal of progressing to cirrhosis next. This episode suggests an entirely different approach.

The episode starts by discussing the complexities of treating cirrhosis and evolves into a discussion on why compensated cirrhosis might be the BEST place to achieve fast, successful drug development today.

Key moments include:

10:12 - Why discuss cirrhosis?

11:40 - Challenges in cirrhosis treatment and drug development

13:08 - A changing viewpoint on cirrhosis as drug development target

17:24 - NASH and cirrhosis disease progression

20:10 - Diagnosing and stratifying cirrhosis patients

24:20 - NITs might make cirrhosis a better drug development target than F2/3

30:06 - Building momentum to reconsider NASH and cirrhosis drug development

33:47 - Identifying the conceptual road block in the move toward NITs in cirrhosis

39:09 - Formulating a plan of action to strengthen cirrhosis drug development and treatment

40:53 - A "disruptive technology" to pool clinical trial results

44:28 - The challenge: pushing cirrhosis treatment and drug development forward

50:09 - Business section

Professor Arun Sanyal and Stephen Harrison provide a 40-minute briefing on fibroblast growth factor (FGF) agents and why they are so important to the future of NASH and NAFLD therapy. This conversation detours into health policy and screen fail rates before returning to consider the 2-5 year implications of FGF drug therapies.

After a simple opening from Roger Green, this conversation includes 4 key elements:

Health Policy

1:24 - Arun Sanyal discusses directions that Fatty Liver policy in India is heading, along with some its unique features (for example, focus on rural health)
2:58 - Louise Campbell discusses the gap between how the best British programs (as identified in Jeff Lazarus's paper) organize and operate as compared to what the recent British Liver Trust study tells us about overall Fatty Liver care in the U.K. After Roger makes a commitment to return to health services policy in future episodes, Louise asks a question about how high screen fail rates appear to be in this study. Stephen Harrison notes that these are not particularly high for a NAFLD or NASH study and explains why.
7:28 - Roger asks his final question, which is how panelists believe FGF 21s will be used 5-7 years from today. Arun Sanyal provides the first answer, which looks at FGF-21s and NASH in the context of metabolic diseases and discusses how GLP-1 and SGLT-2 agents that were originally indicated solely for Type 2 Diabetes have broadened indications and use by demonstrating benefit in related non-communicable metabolic diseases,
10:05 - The other panelists add smaller points to Arun's exceptional and global statement. Stephen concurs completely with one important addition: If FGF-21s demonstrate potent anti-fibrotic effects in NASH patients, this will give them a unique role in first line therapy. Louise follows up with her belief that uptake of these agents might mimic some of the Hep C drug and Roger concludes by saying that the entire range of FGF effects is not widely known and, as a result, it is difficult to predict how widespread use might be.

Professor Arun Sanyal and Stephen Harrison provide a 40-minute briefing on fibroblast growth factor (FGF) agents and why they are so important to the future of NASH and NAFLD therapy. This conversation focuses on the roles fibroblast growth factors (FGFs) play in fat metabolism, appetite and other issues related to Fatty Liver disease.

 After a simple opening from Roger Green, this conversation includes 4 key elements:

1:06 - Arun Sanyal discusses the different ways that fibroblast growth factors work in the body
4:21 - Stephen Harrison share some background on how fat gets into the liver in the first place
6:16 - Arun Sanyal describes the specific differences between FGF 2, 3 and 4 receptors in terms of physiologic impact and the role of adiponectin
9:50 - Stephen Harrison and Arun Sanyal comment briefly on the impact of adiponectin in terms of liver scarring

Professor Arun Sanyal and Stephen Harrison provide a 40-minute briefing on fibroblast growth factor (FGF) agents and why they are so important to the future of NASH and NAFLD therapy. This conversation focuses on FGF drug development to date.

After a simple opening from Roger Green, this conversation includes 4 key elements:

1:05 - Roger Green discusses recent history of FGF agents and podcast episodes discussing them
2:11 - Stephen Harrison discusses the efruxifermin BALANCED Phase 2a trial in F2/F3 NASH and Cohort C with cirrhosis patients
6:59 - Arun Sanyal and Stephen Harrison discuss future prospects for FGF-21 agents
10:34 - Arun Sanyal discusses specific receptor targets for different FGF agents and why they matter

This episode has specific discussions of efruxifermin and mentions of pegbelfermin and MK-3655, the former NGM-313.

Professor Arun Sanyal and Stephen Harrison provide a 40-minute briefing on fibroblast growth factor (FGF) agents and why they are so important to the future of NASH and NAFLD therapy.

This discussion combines a discussion of the role Fibroblast Growth Factors (FGFs) play in the liver and human body in general, followed by a discussion of what this implies for drug development in general and some of the specific agents currently in testing or market:

0:15 - Opening quotes - Stephen Harrison, Arun Sanyal, Roger Green

2:07 - Episode begins

2:57 - Meet Professor Arun Sanyal

4:47 - Quick Look at Health Systems and Policy: India, UK, future episodes - Arun, Louise Campbell, Roger

8:16 - Icebreaker and episode set-up - Roger and panel

13:07 - Efruxifermin trials - Stephen Harrison

18:00 - How FGFs work -- Arun Sanyal

21:13 - Liver pathophysiology and insulin resistance -- Stephen and Arun

28:13 - Q & A comparing agents in development - Roger, Louise Campbell, Arun and Stephen

42:09 - Roger offers two choices for the episode's Final Question. Arun provides an exceptionally thoughtful and thought-provoking answer.

The discussion itself includes three elements: first, a discussion of recent efruxifermin trials; second, a discussion of how FGFs work in the liver and rest of the body; and third, comparing and contrasting the various FGF-21 and FGF-19 drugs that are in development (or have been discontinued).

Quentin Anstee, Louise Campbell, Stephen Harrison, Mazen Noureddin, Ian Rowe and Roger Green convene to review #ILC2021 and share key takeaways and insights. This conversation covers issues around drug development.

The conversation addressed the various ways that the challenges that the COVID-19 pandemic created for clinical trials in 2020 played out in the drug development presentations at #ILC2021: a higher level of retrospective analysis of earlier trials and relatively few pieces of novel Phase 2b or Phase 3 research adding to knowledge and insight. The group noted that cirrhosis received relatively more attention and even some fresh data as with the efruxifermin late-breaker publication. Finally, the group discussed some of the studies and insights we can expect to see between now and 2022.

Key opinion leaders Quentin Anstee, Mazen Noureddin and Ian Rowe join Stephen, Louise and Roger to discuss the major lessons and dangling questions from #ILC2021.

The group shares perspectives, insights and questions on four key topics: diagnostics (including both non-invasive technologies and AI/machine learning), drug development, patient populations and policy.Mixed in here you will find discussions on food insecurity, polygenic risk and multi-disciplinary medicine. A great session to hear if you are still organizing your takeaways and questions emerging from the Congress.

Donna Cryer, Vlad Ratziu, Michael Charlton and Mazen Noureddin join Roger Green in reviewing the final day of #ILC 2021.

The conversation revolved around three themes: non-invasive tests as presented at the morning LITMUS session; two promising but incomplete drug trials for a new class of agents and a possible therapy for controlled cirrhotics, and the opportunities and challenges presented by digital meetings (with kudos to EASL for all the platform elements they strengthened from 2020).

Incoming EASL Secretary General Prof. Thomas Berg, Global Liver Institute President and CEO Donna Cryer and Genfit Head of Global Diagnostics Suneil Hosmane share their unique perspectives on Digital ILC 2021 with Roger Green.

In our lead-in episode for #ILC2021, Roger Green conducts interviews with three leaders, each with a unique perspective on what they value about this week's Congress. Incoming EASL Secretary General Prof. Thomas Berg discusses his view on the various ways the Congress will enrich knowledge and interaction in the global Fatty Liver community. Global Liver Institute President and CEO Donna Cryer shares the many ways that ILC has made patients and advocates feel they are welcome at the Congress and capable of making a contribution. Finally, Genfit Head of Global Diagnostics Suneil Hosmane identifies several areas of knowledge that he considers in assessing commercial opportunities. This can serve as a helpful introduction to the Congress or an opportunity to process what you have just seen and learned.

Jörn Schattenberg, Stephen Harrison, Louise Campbell and Roger Green identify specific sessions and presentations they believe will bring the greatest enlightenment around tough challenges and unaddressed issues in Fatty Liver disease.

The topics the Surfers identify vary greatly, from cirrhosis to NITs to public policy issues such as the relationship between food insecurity and NAFLD prevalence. The range of these topics speaks to the breadth and vitality of Digital ILC 2021, as do changes in the digital platform that allow for real-time interactions between attendees.

 Stephen Harrison and Jörn Schattenberg discuss what the titles of Digital ILC 2021 presentations tell us about possible findings in drug development.

Drug development presentations will occur throughout Digital ILC 2021, ranging from late-breakers to general session presentations to dedicated sessions. Stephen and Jörn use the titles of presentation to discuss areas of drug development, paying particular attention to treating cirrhosis on one end and drugs that address defatting the liver through metabolic modes of action.

 Joern Schattenberg joins the Surfers to identify exciting presentations and sessions from the Digital ILC 2021 meeting.

 Digital ILC 2021 kicks off one week from today, with four days of sessions covering the entire range of liver topics. Professor Schattenberg joins Dr. Stephen Harrison, Louise Campbell and Roger Green in identifying presentations, sessions and major themes they believe will import new knowledge and even change the ways we look at NAFLD and NASH. Want to get revved up for the Congress? Listen here.

EASL Scientific Committee member Luca Valenti joins the Surfers to "crystal ball" potential key outcomes from Digital ILC 2021.

The four panelists each predict one likely outcome from Digital ILC 2021. Interestingly, none of them focus specifically on clinical trials, but instead on a broader range of issues around understanding the metabolic underpinnings of NASH and determining treatment plans and strategy for today, before the new generation of medications arrives.

Roger Green narrates a series of interviews, conversations and viewpoints about NGM Biopharmaceuticals discontinuing its F2/F3 aldafermin program

The SurfingNASH team weaves interviews, conversations and text notes from 9 stakeholders, including US and EU KOLs, program heads, treating physicians, patient advocates and NASH patients into a narrative addressing key issues. Was the ALPINE 2/3 trial a clinical failure? What commercial considerations might have played into NGM BIo's decision? What lessons can we learn about clinical development strategies? NITs vs. biopsy? When to trust headlines and when not. There is a great deal to unpack in a 25-minute episode.

Mazen Noureddin returns to discuss the roles different drugs and drug classes will play in NASH therpy after current Phase 2b and Phase 3 candidates have been approved. This conversation lays out basic premises. 

In this conversation, Stephen Harrison and Mazen focus on how treatment guidelines and therapeutic choices might vary for patients starting at F2 vs. F3 vs. compensated (maybe even decompensated?) cirrhosis. One key issue is "de-escalation" -- whether guidelines will suggest treating with agents that are more potent injectible anti-fibrotics for later stage patients, then retreating to orals with broader metabolic effects when patients' fibrosis has regressed to F2 or F1. The subject of "backbone therapy" comes up for the first time here, although it will be in later conversations of this episode as well. Louise Campbell and Roger Green round out the conversation with questions and observations. There is a lot to unpack here, so listen, learn and enjoy.

Mazen Noureddin joins the Surfers to explore the issues and needs that will shape treatment guidelines in a world after NASH drugs come to market.

In Season 2 Episode 16, a discussion of cost-effectiveness led to the question, "How will treatment pathways and rules evolve as new NASH drugs come to market." Mazen Noureddin, who raised this issue with Stephen Harrison in the earlier episode, returns to explore the answer ten episodes later.

The discussion considers what the phrase "backbone therapy" will mean in the future of NASH therapy and which agent(s) might attain that status. It considers how treatment models might vary for patients with cirrhosis vs. those with NASH, and for compensated cirrhosis vs. decompensated cirrhosis. It explores the role that AI-driven algorithms powered through electronic records will play in helping primary care physicians, general gastroenterologists and general hepatologists (if there is such a thing) treat patient who might have not only NASH but a range of accompanying metabolic conditions.

This discussion covers a lot of ground in a very short time. It stimulates and challenges. Enjoy it!

After having time to think, six of the panelists who covered sessions at the Fourth Global NASH Congress get together one more time to consider key takeaways from the Congress. This conversation is organized around adoption of non-invasive testing in clinical development and when drugs will come to market.

After hearing presentations from 43 speakers at the Fourth Global NASH Congress, six SurfingNASH panelists convene once more to debate how long it will take before we have new medicines to use in identifying and treating patients. This is related to the question of when FDA and EMEA will accept non-invasive tests in pivotal trials. There was some disagreement on the year in which events will happen, but not on the basic pattern of market evolution. 

Manal Abdelmalek and Ian Rowe join Roger, Louise and Donna to review the morning that Vlad Ratziu and Michael Charlton both identified as the highlight session of NASH-TAG 2021. 

The Friday morning session of NASH-TAG 2021 highlights advancing research for five major NASH drugs in development, explores the question why drug trials fail and wraps up with a rapid-fire session on promising data. Surfers were excited about some of the new drugs and found the presentations from Vlad Ratziu and Mary Rinella about why cirrhotic and non-cirrhotic drug trials fail to be particularly powerful and well-presented. 

After the session, join SurfingNASH to sort out how what the data means, how the pieces fit together and what questions will require more exploration. If you send us any questions emerging from Session #1 or the podcast, we will try to review them during later NASH-TAG episodes.

Stephen Harrison previews NASH-TAG 2021, the pre-eminent NASH drug development meeting, which will take place from March 10-12.

This year marks the 5th annual NASH-TAG, a meeting focused solely on NASH drug and diagnostics development. The NASH-TAG format calls for "deep dives" into key issues and combines innovative presentation formats with debates on pivotal issues. Stephen Harrison walks Louise, Roger, and our guest Ian Rowe through the agenda. The panelists raise provocative questions about the agenda, and wander into informative conversations about how knowledge develops and how responses to the COVID-19 vaccine may prove instructive in motivating patients. Lots to think about here...and good motivation to register for virtual NASH-TAG.