Thursday, June 9, marks #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. With over 200 affiliated organizations and sponsors, many holding their own events, International NASH Day is not only a major day for education and communication, but also in a sense NASH's "New Year's Day," a moment to take stock of the last year and make resolutions for the future.
To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.
Stephen went first, focusing on a pivotal change in Phase 3 trial design. Unti now, corporate sponsors have conducted one large Phase 3 trial with F2 and F3 NASH patients. The initial phase of the trial would include 1,000 - 1,200 patients with the goal of achieving sub-part H approval based on conditional endpoints. This trial would keep enrolling patients until there were enough patients in the trial for 4-7 years to prove an outcome-based endpoint and achieve full approval. In the new design, two trials transpire in parallel: the original trial with F2 and F3 patients and a trial with well-compensated cirrhotic patients focused solely on achieving an outcome. This design should prove easier to recruit, less expensive, and more likely to achieve outcome-based endpoints more quickly. Also, it allows the sponsor to evaluate "co-endpoints," as Stephen puts it, instead of needing to achieve dual endpoints. This way, the sponsor can succeed by achieving fibrosis improvement with only a stable NAS score or a decline in NAS score with no worsening of cirrhosis.
All three panelists expressed admiration and appreciation for the benefits of this approach. Stephen noted how many people needed to collaborate for this to come to fruition and how much more collaboration is taking place in the community.
Jörn went next, focusing on the extraordinary breadth in focus and content of pivotal conferences during the year. He mentioned the fireside chat with regulators at NASH-TAG and the broad discussions in Barcelona exploring how best to serve patients after we have a drug.
Louise focused on systems thinking, mostly related to diagnostics, focused on how best to use non-invasive methods to screen, diagnose and stage patients. What she found striking is that these discussions are taking place before drugs are approved, which suggests the possibility that shorter after we have drugs to prescribe, we will have systems and protocols to get the drugs to the patients that need them most. Louise contrasted thought development in NASH to Hep C, where the drugs came along before we knew how to find the patients.
Rounding out the group, Roger talks about the Law of Unintended Consequences and the Intercept Complete Response Letter from FDA. He recalled the initial thoughts that the failure to approve obeticholic acid would signal a perilous downturn in interest in Fatty Liver disease. Instead, he suggested, the passion of the community coupled with lack of funds led stakeholders to ask better questions and focus on more practical issues, which has led to the convergence we are seeing today.
As the conversation wound down, Stephen and Jörn noted that providers will not tolerate "No" for an answer, recalling patients who suffered from HCC and died too young.
In the end, Roger asked the group to make a bold predictions about what will happen next year, when the group gets together on the eve of International NASH Day once again to survey the past year. The predictions were bold and optimistic. You will need to listen to or view the episode to learn what they were.
