Global Liver Institute Founder and CEO Donna Cryer and Key Opinion Leader Professor Scott Friedman joined Roger Green at NASH-TAG 2022 for a fast-moving, far-reaching conversation on drug development and scientific advances in Fatty Liver disease.

This episode includes the entire discussion, plus a shorter conversation with Roger and patient wellness advocate and SurfingNASH co-host Louise Campbell focusing on some of the lessons emerging from NASH-TAG’s first day.

2:17 – Roger Green introduces the agenda for today’s episode
5:25 – Actual conversation begins
5:42 – Donna Cryer: “Favorite phrase” from the NASH-TAG Day 1 is “lessons learned”
7:02 – Scott Friedman on NASH-TAG Day 1: equal parts sobering and promising, with a major conceptual change
7:34 – Scott’s “sobering” points: highly anticipated clinical trials “did not pan out;” “we don’t know where this disease starts” or where to start treating it; and “we tend to approach the disease as one size fits all”
9:06 – Scott’s “promising” points: digital histopathologies, gene regulation and epigenetics, diagnostics, organoid technologies and more
11:33 – Roger: We need to think of “combination” treatment strategies not only in terms of static same-time combinations but also sequencing of medications as replacements or add-on combinations
11:57 – Roger: Vincent Wong did well to describe NGM discontinuing aldafermin in non-cirrhotic NASH as commercial, not clinical, decision
12:58 – Donna: To de-risks trials, include patients when setting objectives and goals and designing trials to achieve them
14:42 – Roger: This is more valuable for smaller companies whose budgets require more narrowly focused trials
15:28 – Scott: One other element to consider is patients’ “disappointment when things don’t work.”
16:20 – Donna: Patients realize the first drug “doesn’t have to be perfect”
17:13 – Donna: Interdisciplinary discussions at NASH-TAG are a very hopeful development
18:04 – Scott: learning about the underlying biology makes me hopeful, even though we do not know which elements matter most
18:42 – Roger: the double and triple agonists appear very promising in terms of weight loss potential with acceptable side effects
19:10 – Scott: Weight loss reverses a biology we can’t seem to accomplish with drugs, but the body fights efforts to maintain lower weight
20:18 – Donna We need multidisciplinary, multifaceted approaches that do not rely on patients’ willpower
21:11 – Donna: Key is to pull together all the elements we know to create complete care approaches that work for different types of patients
22:24 – Scott: “Personalizing” is not just about therapy, but also how the patient copes with the disease
23:02 – Donna: I remember early in my care being jealous of cancer patients for the holistic care they were able to receive that liver patients weren’t
24:48 – Roger: My experience as a cancer patient taught me that drugs need to be tolerable
25:55 – Donna: Do we believe that pruritis will continue to be an ultra-rare indication when it is implicated in so many liver diseases?
26:25 – Scott: Companies are developing new, more elegant biologic definition of the processes that cause pruritis, which should lead to better therapies
26:42 – Roger: One thing that makes oncology different is that ONCs are willing to experiment out of label with medications. Will we see more of this in hepatology, specifically Fatty Liver?
27:16 – Scott: Hepatology is a more conservative community and NASH is a far slower moving disease
28:04 – Scott: In more urgent and symptomatic cases, hepatologists have been as creative as they can, but nothing has worked so far, given the limited underlying biologic understanding
28:59 – Donna: When they are approved NASH drugs will be prescribed in a polypharmacy setting and for patients who have multiple healthcare costs. I hope manufacturers will act responsibly.
30:14 – Donna: Pricing for pruritis agents might inspire a backlash. Patient advocates will not support current pricing.
31:01 – Roger: Keep in mind that modeling comes from finance departments are targets cash management and budgeting issues
31:34 – CLOSING QUESTION: What do you believe will change in the next year and what do you hope will change?
31:40 – Scott: Hope to see a drug trial result that will get over the finish line. Expect to see advances in NITs and digital histopathology
32:41 – Donna: Hope and expect two things: alignment between advocates, researchers, manufacturers and regulators on what mark we need to hit and what will happen once we hit it, and clarity around best use of NITs
33:31 – Roger: Expect to see adoption of digital histopathology in 23, maybe even end of next year. Hope to see widespread acceptance that stabilizing fibrosis is a perfectly acceptable clinical outcome for drugs.
34:33 – Scott: We’ve known all along that FDA considers non-progression from advanced fibrosis to cirrhosis an acceptable endpoint.
36:03 – Louise and Roger chat about fine points from NASH-TAG sessions and the first part of S3 E2.
45:55 – Business Section