Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). On the last full day of the program, several vitally important drug development studies were presented during the late-breaker and dedicated sessions. The conversations in this episode will review some of the most important findings
This particular conversation discusses two presentations on resmetirom, the late-breaker safety results (and some preliminary, secondary efficacy markets) from the Phase 3 MAESTRO NAFLD-1 trial, and a separate study looking at 180 cirrhotic patients in the open-label cohort of MAESTRO.
MAESTRO NAFLD-1 was a double-blind, randomized, placebo-controlled trial of 80 or 100 milligrams of resmetirom versus placebo, with close to 1,200 patients in these three cohorts. There was a fourth 100mg open-label cohort as well, with 180 cirrhotic patients among the trial population. For MAESTRO NAFLD-1, the primary endpoint was safety. In addition, there were several key secondary endpoints, including pathogenic lipids, certain MRI characteristics, along with along with FibroScan (both KAP and KPA). To primary author Harrison, the “take home point” from this study was “there was no bad news from MAESTRO NAFLD-1, and it did meet its primary endpoint with all the key secondary endpoints under hierarchical control having statistical significance as well.
One more interesting point from this presentation. Because the study was fielded during the COVID-19 pandemic, patients in the three closed-label arms missed an average of two months of doses due to pandemic-related logistical challenges. Despite this, the secondary endpoints demonstrated efficacy, although some demonstrated reduced efficacy compared to what we would expect from a full course of therapy.
Stephen then shares significant data from the first 105 patients in the open-label cirrhosis group. Without going into detail, the “take home point” here is that “in addition to the safety and tolerability… we were moving noninvasive tests in a way that made us feel like something positive was happening relative to maybe some early portal hypotensive changes.” Stephen notes the caveat that the researchers performed neither endoscopy nor HPG measurements in this population.