In advance of NASH-TAG 2022 this weekend, Jörn Schattenberg joins the Surfers to answer a key conference question: are we ready to pivot toward non-invasive tests and better uses of histopathology? The group explores a range of questions and ideas that are likely to emerge during Saturday night’s fireside chats.
The group explores a range of questions and ideas that are likely to emerge during Saturday night’s fireside chats.
7:03 – Stephen Harrison begins to discuss NASH-TAG 2022
7:45 – Jörn Schattenberg: we’re not ready to move beyond biopsy in 2022. Hope that we will bring forward the right program by end of the year
8:31 – Roger agrees
8:43 – Stephen agrees, but looks to determine how to resolve pivotal challenges
9:46 – Stephen lists discussants for the fireside chats, including regulators, researchers and industry representatives
10:30 – Stephen lists key topics for his talk on non-cirrhotic trial endpoints
11:37 – Stephen lists “hurdles” biopsy “needs to overcome”
12:40 – Stephen’s key issue for histopathology: why we only score one H&E and one tri-chrome read per sample. He suggests three H & E and promises to reveal data on this in his talk.
15:08 – Jörn: “Why three?”
16:08 – Stephen: no magic, three non-contiguous reads “just makes sense.” The goal is to find ballooned hepatocytes or clustering, which might not appear in one slide but will frequently appear elsewhere in the sample.
18:11 – Stephen: choose the slide with the strongest presence of disease
18:47 – Key benefit: we screen fail fewer people on ballooned hepatocytes
19:59 – Potential secondary benefit: reducing resolution scores in the placebo group
21:09 – Stephen: three companies looking at this. All see a major difference.
21:29 – Stephen: there are commercial issues as well: high screen fail rates inflate costs and take lots of time. This approach will save money and time.
24:13 – Stephen: I like Jörn’s idea about using AI here. It will enhance reproducibility.
24:52 – Stephen: another issue is the shift from one to multiple pathologists. Multiple pathologists turn out to drive screen fail rates higher. We need something to counter that.
26:49 – Louise Campbell: getting more tissue is beneficial for the patient
27:52 – Louise: a lot of NIT evaluation comes from pairing to biopsy samples. The more samples, the more opportunity to test NITs.
29:14 – Stephen shifts to getting beyond the biopsy. FDA issue: link an NIT to an outcome. The cirrhosis chat gives us our first shot on goal.
30:55 – Stephen: one challenge with non-cirrhotics is that NITs are not included in the major Phase 3 trials
32:07 – Jörn: this is a pivotal issue and NASH-TAG is the right place to discuss it
33:33 – Louise: consider quality-of-life as a high-value outcome measure
33:57 – Jörn: how do we explore stabilization of disease with NITs?
34:31 – Stephen: all these are reasons to “set the stage” with cirrhotic cohorts first, learn the lessons, then extend to non-cirrhotics
37:56 – Closing question: what will make 2022 successful to you in terms of moving this agenda forward?
38:17 – Jörn: data from the consortia
38:50 – Stephen: a clear idea of what will get us to a surrogate endpoint with NITs. Until then. improve histopathology practices.
39:54 – Louise: anything with histopathology that leads us toward NITs is good. Also, we will need to do more remotely as long as COVID keeps rearing its head.
40:51 – Roger: let’s learn more and make two cases one on economics and the other on data quality
41:17 – Stephen: one more thing: better economics and stronger data will motivate Big Pharma to invest
43:53 – Stephen: at the end of the day, it’s all about economics
44:53 – Roger: burnt money feels wasted, makes study investment feel like an expense
46:09 – Stephen: listen for more Saturday night
47:16 – Business report