regulatoryscience

This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute).

In this final conversation, Roger prompts the group to share additional takeaways from the meeting that they feel would be valuable for the audience to review in the published slides. Michelle shares that the meeting strongly made clear the importance of collaborative thought and grappling with different perspectives while guided by patient needs. Jeff states that while it’s easy for the community to become self-congratulatory on the precipice of a first drug approval, he saw how approvals will morph and magnify challenges, particularly in terms of clinical trials going forward. Roger highlights how the meeting reframed for him the narrative around patient journey. Lastly, Veronica voices her appreciation for all forms of feedback which will help the Forum “push the science, push the thinking, and push the innovation to make things happen.” 

If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.


Stay Safe and Surf On!

This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute).

Roger leads this conversation by asking the panelists to pick a particular session that captured their attention in a way that could not have been predicted. Michelle first mentions how the agenda as a whole illuminated the depth of the issues surrounding drug development for the fatty liver field. Veronica points to an interactive session titled NASH Drug Development in the Era of Approved Drugs, commending friends of the podcast Manal Abdelmalek and Pamela Danagher for their brilliant moderation. She says that hosting an unscripted panel in a safe environment with engaged participants is a way to “push the envelope and move the field forward.” Jörn notes data presented from the European Heart Journal as an exciting example of exploring and utilizing literature from outside the liver field. At this point, Mazen offers a more tangible description of some content covered. He details general concepts behind a session on Cirrhosis Working Group Updates which included his presentation on Compensated Cirrhosis Risk Stratification. As the conversation winds down, Veronica reminds that the slides from the event are published on the Liver Forum website and well worth a review. 

If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.


Stay Safe and Surf On!

This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute). Veronica leads this conversation with a recap of how the Forum aims to advance the regulatory sciences for the treatment of NAFLD/NASH and liver fibrosis by providing an independent and neutral venue for multi-stakeholder dialogue. She underscores the importance of being able to convene as a community to discuss how drugs get researched and approved, and how patients participate in this ongoing process. Jeff notes that patient involvement has increased with each successive year and points to a panel discussion following a presentation on OCA Program Learnings that featured a patient representative. Veronica later comments on the Forum’s history of representing patient voices at both an organization and individual level. Michelle reminds that “at the end of the day, it's about making people feel, function and survive better.” From the patient perspective, halting progression and stabilizing disease are significant quality of life components for treating NASH. Jörn agrees that this message around stabilization of disease can be better amplified before describing how the energies of the meeting carried through to Europe where he was attending remotely. Roger, who also attended remotely, comments positively on the cohesiveness of the program. Finally, Mazen introduces a few of the specific scientific topics explored. Namely, he touches on cirrhosis, the future of combination therapy, clinical trial design and a session on statistics which proved entertaining with charismatic presenters. 

If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.


Stay Safe and Surf On!

NASH-TAG 2023 proved to be a watershed moment for Fatty Liver disease as exciting drug development readouts, powerful academic work on non-invasive tests and the willingness to dive into the toughest questions aligned in Deer Valley, Utah. In this weekend’s conversation series, Surfing NASH reviews its diverse coverage of the conference by showcasing key excerpts across six recordings with various KOLs, patient advocates and stakeholders.

This conversation consists exclusively of an exchange between Donna Cryer and Roger Green. The session begins by Donna noting that while the data is cause for enthusiasm, she is concerned that this alone does not guarantee an inevitable approval. In addition to good data, she suggests, is the need for good regulatory science. As she points out, Intercept hit its endpoints in 2020, yet no approval was gained at the time. “Good regulatory science” is, in her words, conclusive, granular and contains a simplified message. Roger asks for an example of what might not constitute good regulatory science. This leads Donna to recall that the fireside chat, although titled regulatory, focused more on clinical trial designs than how to prepare for advisory committees, health technology assessments and Phase 4 trials. She notes that during this discussion, a good question surfaced regarding how equipoise will change once drugs are approved. The implication: what FDA is currently seeking in Phase 4 becomes unrealistic once drugs reach the market. At this point, Roger returns to Scott Friedman’s comment about the “straitjacket of biopsy” and how that impacts thoughts around trial design and “proof.” Donna adds that real-world evidence is the up-to-date approach these days, and it will be available once we have more experience with the medicines. 

As the session winds down, Roger goes back to the adiponectin analyses predicting non-response as being his favorite part of the meeting and explains why. Donna shares that one of her favorite moments came when Claude Sirlin, a radiologist, asked how they can become more involved here. Roger responds that radiology may succeed biopsy as a “hard standard” of efficacy. In the final moments, Donna discusses some of the presented data and questions that embodied a public health perspective. 

For our look back at NASH-TAG 2023, Jörn Schattenberg and Roger Green are joined by Amy Articolo and Naim Alkhouri for a discussion which dives into the therapeutic efficacy of recently announced data on resmetirom, NITs, bariatric surgery and more. Adjoining this session is a bonus interview with Donna Cryer on her impressions and key takeaways which largely look into the movement of regulatory science. In combination, this two-part episode encompasses contrasting and thought-provoking perspectives on addressing the opportunities and challenges in moving the Fatty Liver field forward.

Naim opens the first conversation by noting the positivity emitted, echoing Scott Friedman’s position that momentum from Madrigal’s emerging data on resmetirom animated the wider program. In addition, he highlights that granularity around Intercept’s study of patient response to obeticholic acid (OCA) revealed improvements among the F3 population. For Naim, OCA is a drug he has envisioned to be applied toward advanced disease and serves undermet needs of F3 patients. He concludes that in the wake of these aforementioned results, there remains plenty of opportunity to improve and other biotechs “are still in the game” with the energy to back them.

At this point, Jörn underscores the strong presence of academia and involvement of various consortia as further evidence of progress. Amy joins to comment on the vibrant and dynamic discussions around NITs and how to enrich trials. She suggests that the dialogue has reflected the advancements of the field and how work can be enhanced with collective contribution. This leads to thoughts on pharmacodynamic change and demonstrating value to payers. Roger distills a main idea: if only 24% of patients show a one-level regression of fibrosis in a given period of time, there is much to learn about the other 76%. Conversation continues around narrowing the indeterminate zone and improving biomarker concordance in NITs. After exploring considerations in moving beyond biopsy, the group investigates the role of bariatric surgery. While recognizing the validity of bariatric surgery as a treatment option, Naim points to a brighter future of preventative hepatology whereby action precedes BMI levels of 50 and higher. At the end of the session, Roger asks each panelist for one unexpected thing that might happen in the next year.

In the following interview, Donna opens with a powerful statement: hope is not a strategy, and optimism is not inevitability. Specifically, she is determined to match the trajectory of regulatory science to that of the momentous energies emerging from clinical science. In doing so, relationships and open lines of communication are key for meeting agreed endpoints. Next, the two talk about addressing the indeterminate zone in a different context and opportunities for harnessing real-world evidence. As this conversation moves forward, it becomes clear that Donna is committed to connecting patients to care today, and not only after a drug approval. In closing, she fields the same question as the preceding panelists, but offers a very different answer. Surf on to find out.