S3-E4 - NASH-TAG 2022 Wrap-up: What Did We Learn about Fatty Liver Disease and Clinical Trial Design?

Send us Fan MailSurfingNASH invited four attendees to the NASH-TAG wrap up (three first-timers, two corporate executives) to focus on presentations and discussion from the fireside chats. Highlights include:4:20 – Introduction of first-time panelists Amy Articolo (Novo Nordisk), Erin Quirk (Terns Pharmaceuticals), Rachel Zayas (AGED Diagnostics) and the returning Ian Rowe (University of Leeds)12:55 – Opening question: what about NASH-TAG 2022  surprised you most?13:04 – Consensus: energy and passion. Rachel mentioned the vast divergence in  balloon hepatocyte readings16:19 – Led by Stephen, group discusses powerful single slides22:51 – Question: What single presentation had a real impact on your thinking?23:04 – Rachel: Single Cell Transcriptomics, which can identify disease drivers. 25:53 – Ian: Scott Friedman’s point about the need to balance blocking fibrosis with maintaining sufficient collagen for scar healing.27:16 – Amy: Talks about upstream effects resonated because Novo Nordisk works to develop combination therapies.28:53 – Erin: One “pleasant takeaway” was big companies sharing findings “shoulder to shoulder” with smaller ones.30:04 – Roger: Rate reaction to fireside chats using 6-point scale. Erin, Amy, Rachel all say 5. Liked diverse viewpoints, high energy level. Ian says 4, maybe 3. Fears that following the path laid out in meeting will lengthen drug development. 36:06 – Stephen: We need to improve use of histopathology, design and implement a multi-year path to NITs as outcome drivers and develop NAIL-NIT, a multi-company, “agnostic” data repository to utilize everyone’s data to “ask the big questions” and drive large prospective trials. Also, we should provide analytics and perspective on unresolved issues that are delaying final FDA guidance document47:02 – Amy: Key is to impact patients’ lives, which is more “function and feel,” less survival. We’ll look back on this as "The moment of change” 48:59 – Roger: FDA has becoming more open and encouraging since 01/21 webcast 50:33 – Roger: Stephen’s push to lower screen fail rates from 80% to 50% will drive 2.5x increase in eligible patients, thus shortening trials, reducing costs 52:35 – Stephen: This can also reduce placebo response rates, which are a major issue in interpretation 54:27 – Erin: Should we even be looking at liver tissue when pathologists are so mislaligned on balloon hepatocytes? Stephen: Eventually, perhaps not. But the ongoing trials today have to rely on histology55:02 – Erin: Are we creating medications that patients actually will want to take, given that many choose not to participate in trials? Louise: Decision is individual, but those who take time to make it wisely have the greatest prospects for success57:14 – Ian: Findings from trial populations and natural history populations can vary widely. Also, the NITs we use in trial need to work financially for the larger population59:20 – Amy: Expanding trial population into primary care or OB/GYN would broaden target dramatically1:01:02 – Question: something you hope to see that is different in a year and something you believe you will see1:01:14 – Louise: Patients and advocates at future Fireside chats1:01:29 – Rachel: Tests that look separately at the different NAS elements instead of creating composite scoring1:02:02 – Erin: A positive Phase 3 study result1:02:31 – Amy: Solid and actionable programs to create solutions to issues identified this past weekend1:03:03 – Ian: Expect positive Phase 3 data. Hope to see discussion around NITs that correlate consistently with histology and drive changes in outcomes1:03:21 – Stephen: Hope to report positive Phase 3 trial1:05:04 – Roger: Believe AI histopathology will play larger role; hope this entails more than simply emulating human brain 1:08:03 – Business section