gilead sciences

This episode follows S2 E43 in discussing the possible role of NASH cirrhosis clinical trials in the transition from biopsy as gold standard to a post-biopsy world. Terns Pharma CEO Sen Sundaram joins this conversation from the audience to ask whether the term "cirrhosis" is medically helpful or might warrant replacement with "end stage liver disease." After vigorous discussion on this point, Sen departs and Stephen Harrison leads the group through a review of four ongoing NASH cirrhosis trials. The discussion veers into the issue of which analytics methods designers are specifying and why. At one point, Naim Alkhouri, frequent guest and principal investigator on the Gilead combination agent trial before the session ends. His specific contribution: MRE was not included in the Gilead trial largely for cost reasons.

The most striking fact to emerge from this conversation relates to the "beyond the biopsy" question. MRE is emerging as a highly reliable NIT that appears to produce reliable results regardless of mode of action and is generating correlations and ratios to fibrosis level decreases and other key metrics, yet it is not included in the designs of any ongoing NASH cirrhosis trial. Stephen describes this as the "stovepiping" of data. Companies consider the data they need, not ways it can be aggregated with other trials to solve larger issues. This issue bears further exploration in later episodes.

Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap this week's just-concluded TLMdX 2021, the AASLD annual liver meeting. 

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. That did not happen. Instead, the breadth, quality and novelty of the meeting's presentations generated exceptional positive energy despite the virtual setting. 

4:10 - Roger starts by saluting Manal for giving the NAFLD Wrap-up Talk at TLMdX 2021, then introduces 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 and describes "somewhat surreal" feeling of seeing semi-quantitative histology fail in trials where so many non-invasive markers suggested proof of efficacy
16:13 - Jörn points out the inherent tension between needed accelerated endpoints and being tied to a severely flawed "gold standard" of biopsy
17:15 - Stephen's simplest solution: capitalize on existing study results to link MRE, fibrosis and outcomes
18:56 - Manal counters: this assumes  biopsy is the gold standard, when we know it is seriously flawed
21:02 - Stephen: it's time to "reach a common ground on what it takes to achieve replacement of histology with an NIT"
24:02 - Ian suggests that the FALCON trial history will strengthen FDA's attachment to biopsy
26:13 - Stephen's key to moving beyond biopsy: strengthening the data that supports credibility of NITs
28:13 - Jörn: having a combination of NITs that each reflect different elements of the disease makes 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,  cites story of ALPINE 2/3 as proof
32:17 - Stephen: the path to the data-driven future explodes when the first drug is approved
33:32 - Lars Johansson (Antaros Medical)  joins from audience to ask Stephen whether we can reanalyze spleen volumes from old trials  and reanalyze 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
38:41 - Lars returns to audience
39:25 - Manal returns to Louise's  thought 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 various talks involving the patient-treatment impact of genomics and others implicating genetics as a possible reason for high variability in placebo response between trials.
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
48:12 - Closing question: The biggest story a year from now? Stephen, Manal and Ian focus on "Phase 3 results." Jörn, Louise and Roger focus on ways patient empowerment will focus attention on better patient solutions.
57:05 - Business section

Jörn Schattenberg and Mazen Noureddin join the Surfers to discuss five recently-reported or ongoing clinical trials in NASH cirrhosis. The reviews focus on study findings and their implications, but also on the methods used to conduct each trial and the implications of these designs on generalized learning and ability to move beyond the biopsy.

Stephen Harrison leads the group in discussing recent results from NASH cirrhosis trials, including the REVERSE trial with obeticholic acid, the FALCON 2 trial with pegbelfermin and a post-hoc analysis of Galectin Therapeutics' Phase 2 trial for belapectin. The group also discussed ongoing trials including the FGF-21 efruxifermin, the FGF-19 aldafermin, the Galectin-3 inhibitor belapectin and the combination agent trial from Gilead Sciences. Along the way, Terns Pharma CEO Sen Sundaram joins from the audience to ask whether the name "cirrhosis" is the most appropriate way to define the disease, given all that we are learning. This session takes a deep look at cirrhosis, with focus on clinical trials, disease pathology and patient management.

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).

After having time to think, six of the panelists who covered sessions at the Fourth Global NASH Congress get together one more time to conisder key takeaways from the Congress. This conversation is organized around competing strategies for diagnostic testing as the NASH market evolves.

After hearing presentations from 43 speakers at the Fourth Global NASH Congress, six SurfingNASH panelists convene once more to debate how the diagnostics market will develop. With a profusion of options, physicians, payers and regulators will have decisions ahead. There is some disagreement on the year in which events will happen, but not on the basic pattern of market evolution.

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. 

The SurfingNASH coverage team from the Fourth Global NASH Congress convenes one more time to consider key takeaways from the Congress. Manal Abdelbalek, Naim Alkhouri, Ian Rowe, Suneil Hosmane, Louise Campbell and Roger Green all share high points, opportunities and lingering questions.

On April 28 and 29, 2021, over 175 Fatty Liver stakeholders from across the globe convened virtually for the Fourth Global NASH Congress, and Surfing the NASH Tsunami was there to hear each of 43 speakers and share highlights with our listeners. Now that the Congress has ended and everyone has had time to reflect, the coverage team convenes one more time to consider the implications of what we heard about diagnostics, drugs, non-pharmacological interventions and changing paradigms. This discussion includes controversy and probing questions, all with laughter and camaraderie.

The SurfingNASH Team has curated over three hours of recordings from the Fourth Global NASH Congress to highlight pieces that discuss the current and future states of diagnostics in Fatty Liver disease. You will hear Manal Abdelmalek, Naim Alkhouri, Suneil Hosmane, Ian Rowe, Jörn Schattenberg, Louise Campbell and Roger Green sharing opinions and debating issues.

Discussions about diagnostics ran through SurfingNASH's entire coverage of the Fourth Global NASH Congress. Listen here for some of the diagnostics highlights. The group discusses exciting new precision diagnostics, urine and breath-based biopsies, realistic expectations for diagnostics in market today and implications for clinical trials and patient treatment and other related questions in a fast-moving set of pieces.

Manal Abdelmalek, Jörn Schattenberg and GenFit Global Diagnostics Leader Suneil Hosmane join the Surfers to review presentations from Day One at the 4th Global NASH Congress.

On April 28, over 175 NASH stakeholders from across the globe will meet virtually to hear 23 presentations from leaders in academia and industry. SurfingNASH has selected 11 presentations to discuss in a session we will record right after the conference concludes. The speakers and their broad topic areas are:
Manal Abdelmalek -- innovative non-invasive non-device diagnostics
Jörn Schattenberg -- Developmental drugs that address fructose metabolism
Suneil Hosmane -- Leading edge diagnostic strategies and agents in development
Louise Campbell -- Challenges in using and assessing non-invasive diagnostics in initial diagnosis and secondary/tertiary patient care
Roger Green -- Regulatory perspectives

Jörn Schattenberg and GenFit Global Diagnostics Leader Suneil Hosmane join the Surfers to review non-invasive testing themes to be covered at the 4th Global NASH Congress.

Keynote Speaker Suneil Hosmane joins Louise Campbell and Roger Green to form the coverage team for the 4th Global NASH Congress. In this conversation, Jörn Schattenberg joins them to review non-invasive testing topics covered at the Congress. This conversation discusses advances in technology and the need for non-invasive tests that provide stronger positive predictive value. Listen to get a feel for what commercial, financial and R & D actors can hear about by attending the event on April 28 and 29.

NASH-TAG Co-director Michael Charlton and Ian Rowe join Roger, Louise and Donna to review the morning that Michael himself identified as one of two highlight sessions of NASH-TAG 2021.

The Saturday morning session of NASH-TAG 2021 envisions a world of clinical trials without biopsies, considers implications of enrolling co-morbid and other challenging patients, ands winds up with a debate about the role of diabetes drugs in the future of NASH therapies. 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 #3 or the podcast, we will review them in later NASH-TAG episodes and try to get feedback from those at the meeting.

The Surfers and guests Manal Abdelmalek, Naim Alkhouri and Akero Therapeutics Chief Development Officer Kitty Yale share high-level perspectives on the FDA Webcast, both before and after the group's detailed conversation.

The panel shared overall impressions and key takeaways from the FDA webcast on NASH Drug Development, both before and after the detailed discussion. Key issues included the agency's continued reliance on histology coupled with a willingness to accept digital pathology results, the importance of risk: benefit ratio in drug evaluation, the importance of a composite fibrosis+steatosis endpoint, and new approaches to clinical trials for cirrhosis.

Reviews of Phase 2 drug trials and diagnostic strategies reveal that NASH is close to multiple breakthroughs.

Naim Alkhouri and Mazen Noureddin join Louise and Roger to review highlights from Sunday at The Digital Liver Meeting. Naim, Mazen and Roger review results from drug trials that reveal that multiple drugs (monotherapies and combinations) with potent effects on liver fat reduction and fibrosis are moving through the pipeline. Louise discusses a trial that relies on non-invasive techniques to assess histologic improvement and fibrosis regression in cirrhotic patients, signaling one more way that non-invasive techniques might replace biopsy. Finally, Louise and Roger team up to discuss a US-based 20-year study showing us the many ways that lean NASH prognosis and co-morbidities differ from overweight or obese NASH. A session filled with information, theorizing and high spirits!

In this week’s episode, we focus on Intermountain Healthcare’s announcement that it has formed a “comprehensive health platform company focused on elevating value-based care capabilities.” The new organization, named Castell, will be led by Rajesh Shrestha as president and CEO. Shrestha will continue to serve as vice president and chief operating officer of Community Based Care for Intermountain.

Other briefs include:

• Gilead Sciences’ research and development collaboration with Belgian biopharmaceutical company Galapagos NV, valued at more than $5 billion.
• Genentech’s recent spate of research agreements.
• John Muir Health is forming “a comprehensive relationship” with Optum.
• The closing of Michigan’s Together Health Network.
• Physician participation in CMS’ Advanced Alternative Payment Models doubles in 2018.
• Care New England withdraws from merger discussions with Lifespan and Brown University.
• Memorial Hermann names Dr. David Callender as its new president and CEO, effective September 1.

About Darwin Research Group
Darwin Research Group Inc. provides advanced market intelligence and in-depth customer insights to health care executives, with a strategic focus on health care delivery systems and the global shift toward value-based care. Darwin’s client list includes forward-thinking biopharmaceutical and medical device companies, as well as health care providers, private equity, and venture capital firms. The company was founded in 2010 as Darwin Advisory Partners, LLC and is headquartered in Scottsdale, Ariz. with a satellite office in Princeton, N.J.