-- MAESTRO Phase 3clinical studies proceed, with more flexible allowances in visits and study drug dispensing for enrolled and screened patients at impacted sites, intended to maintain patient safety and trial integrity during the COVID pandemic.

PDFF vs NASH resolution (ROC) PRO-C3/C3M ratio changes - Main/Extension study

-- Abstracts accepted for oral presentations at postponed or cancelled scientific meetings (EASL 2020; AASLD, Emerging Topics, 2020 are described here. Key findings include:

• New analyses demonstrate that liver fat reduction at 3 months after starting treatment has clear predictive power for NASH resolution and fibrosis reduction on subsequent liver biopsy.
• Once daily oral 80 mg and 100 mg Phase 3 doses of resmetirom deliver at least 50% to more than 60% reductions in liver fat, respectively, and, based on new analyses of Phase 2 data, are associated with a statistically significant 64% NASH resolution (p60% had fibrosis reduction.
• New data demonstrate that resmetirom robustly and statistically significantly (p50%) was correlated with a greater than 60% likelihood of NASH resolution with fibrosis reduction. Liver fat reductions at 80 mg and 100 mg, the Phase 3 doses, are impressive with relative: absolute fat reductions of 50%: 9.7% and 64%: 15.7%, respectively, as demonstrated in Phase 2. Available data, including our own, also indicate that liver fat reduction and NASH resolution are directly associated to a reduction in fibrosis.  

  Dr. Stephen Harrison, M.D., Principal Investigator of the study, and Medical Director for Pinnacle Clinical Research, San Antonio, Texas, and Visiting Professor of Hepatology, Oxford University, and Principal Investigator of the MAESTRO studies commented, “There is significant rationale for NASH patients to continue in clinical trials during the COVID-19 pandemic. With their high prevalence of diabetes and metabolic syndrome, NASH patients are at higher risk for developing life-threatening complications from COVID-19 infection. Controlling the liver disease and metabolic risk of such patients may help them survive COVID-19.  Moreover, NASH patients in clinical trials can be well-managed for safety. Because resmetirom is in Phase 3, supported by substantial safety data and has shown benefit in NASH and parameters of metabolic syndrome, I believe MAESTRO trials are well-positioned to maintain enrolled patients in the studies, continue recruiting at unaffected sites and restart quickly at affected sites once the pandemic conditions are alleviated.”

  He added, “I am particularly excited about the high predictive power of liver fat reduction on NASH resolution with fibrosis reduction demonstrated in resmetirom’s Phase 2 study. Moreover, PRO-C3 is a robust non-invasive biomarker demonstrated to be strongly correlated with NASH fibrosis. New analyses show that resmetirom statistically significantly reduces markers (PRO-C3/C3M) of net collagen deposition in the liver further supporting the potential anti-fibrotic action of resmetirom.”

  EASL (European Association for the Study of the Liver) Abstract Publication - Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to predict treatment response on NASH liver biopsy: a secondary analysis of the resmetirom randomized placebo controlled Phase 2 clinical trial. Loomba, R, Bedossa, P, Guy, C, Taub, R, Bashir, M, Harrison, SA

  Summary and findings:

  Resmetirom treatment resulted in significant reduction in hepatic fat as assessed by MRI-PDFF after 12 and 36 weeks that was associated with higher rates of NASH resolution compared to placebo on week 36 liver biopsy assessment. The aim of this secondary analysis was to examine the potential of early reduction in MRI-PDFF to predict histologic response in patients with NASH including both placebo and resmetirom treated patients. The study cohort was assessed for those who had a ≥ 30, ≥ 40 and ≥ 50 % decline in MRI-PDFF between baseline and week 12 as predictors of NASH resolution.  

  To determine the potential predictive power of liver fat reduction on NASH resolution, data were analyzed from 107 NASH patients (n=34 placebo, n=73 resmetirom) with paired baseline/week 36 liver biopsies (read by two blinded central pathologists) and paired baseline/week 12 MRI-PDFFs. Including the MRI-PDFF/biopsy data from both MRI-PDFF responders and non-responders (including placebo patients) the relationship to a NASH resolution response was assessed.

  In patients with NASH resolution, the mean week 12 fat reduction (MRI-PDFF) was 56%. The predictive accuracy was determined by calculating the area under the receiver operating characteristic curve (AUROC) and its 95% confidence intervals (CI)s. The AUROC was 0.89, the optimal MRI-PDFF reduction with best balance of true positive and false negative rates was 41.5% (p