Last week, roughly 5,000 hepatology stakeholders met at the ExCel Centre in London for #ILC2022, the first major hepatology Congress with significant in-person attendance since the start of the COVID-19 pandemic. This wrap-up episode covers some of the major drug development and patient screening themes that emerged from ILC.
The previous ILC2022 episodes spent virtually no time on NASH drug development, so moderator Roger Green starts by suggesting this episode pay specific attention to the medications covered in the late-breaker session and Friday press conference. Stephen Harrison, who presented the resmetirom late-breaker and two other resmetirom studies at the conference, started by talking about the resmetirom late-breaker, which reported initial Phase 3 results from the MAESTRO NAFLD-1 trial. The trial's primary endpoint was safety, with several secondary metabolic endpoints. Stephen describes the drug as "safe and well-tolerated in over 1200 patients treated for one year with 80mg or 100mg versus placebo." On the secondary endpoints, there were "statistically significant reductions in anthropogenic lipids, LDL, APO B ,triglycerides , lipo A" and MRI- PDFF. Also, Stephen notes that because this study took place at the height of the COVID-19 pandemic, patients in the 80mg, 100mg and placebo cohorts missed an average of two months of doses over a 12-month study. Despite this challenge, the drug showed significant effects in MRI-PDFF and MRE. All told, Stephen sees "no bad news" in MAESTRO NAFLD-1.
He shifts focus to the cirrhotic study. Resmetirom was safe and well-tolerated in this population and, non-invasive tests moved in a way that suggested possible movement on early portal hypertensive changes. Stephen notes that the upcoming MAESTRO Outcomes study will allow researchers to learn whether the pathophysiologic changes are linked to outcomes. Mazen and Jörn make generally supportive comments.
Michelle picks up by describing the late-breaker as "generalizable." As she notes, most patients in practice miss doses, which makes these results more akin to real practice. Louise reads this data to say that even in primary care, patients can improve if screened and treated properly.
Jörn takes lead to review the accuracy of biomarkers, specifically ALT and FIB-4. He discusses his presentation based on 2000 liver biopsied patients in the MAESTRO NAFLD-1 population. Of these advanced patients, 26% had normal ALT levels and 80% had ALT levels less than 2x normal. Jörn makes the point that we must find ways not to miss these patients when they appear in hepatology practices since cannot rely on ALT, or even FIB-4, to identify significant disease.
Stephen moves on to discuss the dual GLP-1/glucagon agonist pemvidutide. The pemvidutide study is a Phase 1 with 34 patients focusing on safety and pharmacokinetics. He comments that atherogenic lipids were reduced more than with standard weight loss, points out highly promising results around liver fat, mentions a 14-15% drop in liver volume over 6 weeks and notes a highly tolerable safety/side effect profile. Mazen notes how remarkable he found it that after 12 weeks, 100% of patients on the 1.8mg dose achieved 5% weight loss and 55% achieved 10%.
Jörn shifts the conversation to discuss the semaglutide late-breaker. While semaglutide showed no efficacy in reducing fibrosis for cirrhotic patients over a 48-week period, the group saw positive signs in sema's high level of safety coupled with the ability to meet secondary goals: weight loss, HbA1c reduction. Michelle suggested that this study and others like it might give hepatologists comfort in prescribing GLP-1 today for obese or diabetic patients with NAFLD or NASH. Louise mentions a statin presentation she attended with a similar message about the benefit of non-NASH dru
