This is a 52 week trial. It is 4 times as long as ours.
They are proclaiming safety. We too have the same.
They seem to have efficacy in Early to Moderate Fibrosis after 1 year of treatment.
They are saying they met statistical significance in reductions in steatosis and fibrosis after 1 year using FibroScan.
Common adverse side effect diarrhea.
In the severe patients:
Similar to what we were appreciating, the worse the disease was, the better the improvements were. What is a significant fraction of patients?
They are looking at liver volume reduction. That is likely due to Ballooning. The reduction in Ballooning. That would happen with the reduction in Steatosis. The reduction in Fat. So they seem to be successful after 1 year of treatment in the reduction of fat in order to bring the ballooning down inorder to reduce the volume.
Their end point is a 2 or more reduction in NAS after 52 weeks. We did that in 14 weeks in 2 groups. Regarding PDFF, we did that in the 700 HM group lowering PDFF by 28%. That is a 2 point drop in NAS for the haplotype group. Regarding cT1, we did that in the 350 mg >950 cT1 group by lowering cT1 by 69. That too is a 2 point drop in NAS.
They have a lowering of LDL as a 2ndary endpoint and according to the heat map, we did that in the 700mg HM group only in 14 weeks.
They are still performing their trials, but are getting good safety data and are looking to try to get it expanded for cirrhosis. They are also looking for accelerated approval.
My gut is that they do fairly well in steatosis, but it takes them a year to get there. I don't feel they will do that well in fibrosis.
They may be a good choice for combination with LRM, but I don't know how hard it would be for them to incorporate LRM into their trials. We would only augment and improve their results.
They are proclaiming safety. We too have the same.
They seem to have efficacy in Early to Moderate Fibrosis after 1 year of treatment.
They are saying they met statistical significance in reductions in steatosis and fibrosis after 1 year using FibroScan.
Common adverse side effect diarrhea.
In the severe patients:
Quote:Baseline FibroScan VCTE (kPa 24.6) and MRE (5.7) scores were consistent with F4 fibrosis. Patients with lower MRI-PDFF (≤5%) at baseline had more progressed cirrhosis and greater spleen volumes. Similar to patients with non-cirrhotic NASH, liver volume was greatly elevated compared to normal at baseline.
Resmetirom reduced MRI-PDFF and LDL-C and other atherogenic lipids in patients with NASH cirrhosis and reduced FibroScan controlled attenuation parameter (CAP), VCTE, and MRE in a significant fraction of patients. The largest reduction in FibroScan VCTE (mean reduction of 9 kPa) occurred in the more advanced group (baseline PDFF ≤5%). Similar improvements were observed in MRE.
73% of patients, independent of baseline cirrhosis severity, had at least 15% reduction in liver volume at Week 52. Spleen volume was also reduced and was strongly correlated with liver volume change and exposure to resmetirom.
Reductions in liver enzymes and atherogenic lipids were similar across patient subgroups.
Resmetirom was safe and well tolerated. As observed in patients with noncirrhotic NASH, mild GI adverse events were seen at the beginning of therapy. No differences in safety parameters between patients with cirrhosis compared to noncirrhotic NASH patients were noted. No thyroid axis changes or hyper- or hypothyroid symptoms were observed.
Similar to what we were appreciating, the worse the disease was, the better the improvements were. What is a significant fraction of patients?
They are looking at liver volume reduction. That is likely due to Ballooning. The reduction in Ballooning. That would happen with the reduction in Steatosis. The reduction in Fat. So they seem to be successful after 1 year of treatment in the reduction of fat in order to bring the ballooning down inorder to reduce the volume.
Their end point is a 2 or more reduction in NAS after 52 weeks. We did that in 14 weeks in 2 groups. Regarding PDFF, we did that in the 700 HM group lowering PDFF by 28%. That is a 2 point drop in NAS for the haplotype group. Regarding cT1, we did that in the 350 mg >950 cT1 group by lowering cT1 by 69. That too is a 2 point drop in NAS.
They have a lowering of LDL as a 2ndary endpoint and according to the heat map, we did that in the 700mg HM group only in 14 weeks.
They are still performing their trials, but are getting good safety data and are looking to try to get it expanded for cirrhosis. They are also looking for accelerated approval.
My gut is that they do fairly well in steatosis, but it takes them a year to get there. I don't feel they will do that well in fibrosis.
They may be a good choice for combination with LRM, but I don't know how hard it would be for them to incorporate LRM into their trials. We would only augment and improve their results.
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