Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap this week’s just-concluded 2021 TLMdX, the AASLD annual liver meeting. Discussion centers around the many areas of advance and novelty in the program, with particular attention to non-invasive testing, genomics and the increased visibility of patients and their needs throughout the program.
When AASLD announced that the 2021 TLMdX would be held as a purely virtual meeting, attendees and observers feared a loss of focus and the kind of amplifying energy that comes from being with colleagues. As this episode suggests, the breadth, quality and novelty of the meeting’s presentations generated exceptional positive energy even though colleagues could not meet in person throughout the event. In particular, this group noted the many ways in which the conference format and presentation implicitly challenges some older beliefs and perspectives about NAFLD, NASH and the people who live with these diseases.
Timestamps:
4:10 – Roger Green starts by saluting Manal Abdelmalek for giving the NAFLD Wrap-up Talk at TLMdX 2021
5:16 – Introducing other panelists
6:58 – Icebreaker question: Where did this meeting “make the biggest dent” in Fatty Liver disease?
12:21 – Manal discusses how she organized and prepared for talk
13:17 – Manal describes “somewhat surreal” feeling of seeing semi-quantitative histology fail in trials where so many non-invasive markers suggested proof of efficacy
14:07 – Manal points up first time in meeting that AI provided better clarity than human pathologist reads
16:13 – Jörn Schattenberg points out the inherent tension between needed accelerated endpoints and being tied to a severely flawed “gold standard” of biopsy
17:15 – Stephen Harrison’s simplest solution -“capitalize on working already done” to build links between MRE, fibrosis and outcomes
18:56 – Manal pushes back, “You’re assuming that biopsy is the gold standard” when we know how flawed it is
21:02 – Stephen: it’s time to “reach a common ground on what it takes to achieve replacement of histology with an NIT for a conditional approval.”
24:02 – Ian Rowe suggests that the story of FALCON 1 and 2 will strengthen FDA’s attachment to biopsy
26:13 – Stephen identifies strengthening the data that supports the credibility of NITs as a key activity in this effort
28:13 – Jörn: having a combination of NITs that each reflect different elements of the disease makes this effort easier and more credible
28:45 – Ian: controlled cirrhosis studies might allow quick validation and acceptance
29:35 – Manal: we know how to design better trials now and cites ALPINE 2/3 discordance between consistent NITs and a single disqualifying human histology read as proof that we need to do so
32:17 – Stephen: the path to a far richer, data-driven future explodes when we get our first drug approved
33:32 – Lars Johansson of Antaros Medical, a recent guest, joins from audience to ask Stephen whether we can reanalyze spleen volumes from old trial successes and failures and goes on to suggest reanalyzing imaging data possibly with AI
34:52 – Stephen salutes Lars’s “very good insight” about the potential to reanalyze the “huge” bodies of data from older trials
35:54 – Jörn agrees, but cautions that we need to keep primary focus on getting a drug approved
36:51 – Lars questions whether findings from NITs will limit drug approvals to certain types of drugs vs. being replicable to approve different classes of drugs. Stephen’s eloquent answer comes down to “some will, others will not”
38:01 – Manal concurs with Stephen
38:41 – Lars returns to audience
39:25 – Manal returns to Louise Campbell’s idea that one thing coming from meeting has to do with genomics, citing Million Veteran database
40:16 – Manal describes how single cell RNA data will shape the future of diagnostics and treatment in Fatty Liver diseases
41:10 – Louise refers back to a Friday talk from Yaron Rotman in which he noted that genomics would have limited impact in day-to-day world but real value in assigning patients to clinical trials and identifying those at highest risk, then goes on to discuss other papers having to do with genetics as a possible reason for high variability in placebo response between trials.
42:38 – Stephen supports Louise’s point by discussing diabetic patients and ballooning
43:42 – Stephen raises the diversity inherent in microbiome data as playing a role in making Fatty Liver so complex to characterize and treat
45:10 – Jörn points out that any drug that can “elevate above all these thresholds” and complexities will have to be “quite robust”
46:23 – Stephen envisions the day when drugs are approved based on MRE and the scarcity of MREs around the world creates a new set of challenges
47:37 – Manal observes that “precision medicine has been hot and heavy,” which spurs Roger to note that all the key advances mentioned in the meeting are tied to advances in computing and modeling power that allows us to integrate more data and analyze it better
48:12 – Roger’s closing question: The biggest story coming from 2022? Stephen, Manal and Ian say different versions of “Phase 3 results.” Jörn says momentum around having “everyone at the table” will drive improved care for patients. Louise says having an in-person element in meetings will improve the energy around patient advocacy. Roger says the combination of empowered patients and better NIT and drug data will change most rules…
57:05 – Business section
