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Posted On: 11/04/2021 11:21:18 AM
Post# of 154677
NASH is a huge and open market. It's good to see some preliminary results.
I'm pretty sure they are reporting fat content based on MRI-PDFF and fibrosis based on the MRI cT1 time, at least in the P2 DBPCT:
https://clinicaltrials.gov/ct2/show/NCT04521114
Assume that the open label portion, first N=5, used the same endpoints.
For comparing our results to others, we reported fat down ~5-45% and fibrosis down 0-10%. We can look at recent results from Phase 2 FXR agonist trials measuring the same thing, like from Metacrine:
https://www.globenewswire.com/news-release/20...grams.html
Mean Change (Baseline to Week 16)
Placebo (N=20) 3 mg (N=21) 6 mg (N=20)
Liver Fat Reduction (MRI-PDFF) % ±SD
-7.5% ± 21.0% -26.9% ± 27.8% -9.3% ± 55.8%
Median Liver Fat Reduction (MRI-PDFF) %
-1.5% -28.6% -26.9%
% of patients with >30% Liver Fat Reduction (MRI-PDFF)
11.8% 47.1% 35.3%
The above were actually pretty good results, with median ~25-30% reduction in liver fat content, 35-47% responders vs. 12% placebo, and good tolerability. However for other reasons, Metacrine canceled the program and the stock tanked just a few weeks ago.
It looks like 30% reduction predicts a good clinical response:
https://pubmed.ncbi.nlm.nih.gov/32882428/
Will need to do biopsies for Phase 3 (if our P2 results support going forward).
Lipocine had good Phase 2 results with their NASH drug, a testosterone precursor:
https://ir.lipocine.com/2021-08-25-Lipocines-...LiFT-Study
Their numbers aren't very clear "At 12 weeks, treatments with LPCN 1144 resulted in statistically significant liver fat reduction, assessed by MRI-PDFF, meeting the pre-specific primary endpoint of the LiFT clinical study. Statistically significant reduction in liver fat was observed compared to placebo: up to a mean of 9.2% absolute reduction and a 46.8% relative reduction in liver fat."
"up to"?
They got a FTD from FDA today based on these results.
Madrigal may be the leader in NASH with their resmilteon, with Phase 2 reported here:
https://www.sciencedirect.com/science/article...3619325176
They showed a mean 33% and 37% (12 and 36 weeks) reduction in fat content on MRI-PDFF compared to 10% for placebo. (Amazing in itself to think about how consistent is the placebo effect across NASH trials 10% - how does that work?).
They are hoping to file their NDA 2H 2022 and be first to market for NASH.
It's interesting yesterday's PR says N=90 now. I thought it was originally 50, then 60 (to get more biomarker data?), but now 90? So is it 60 in placebo-controlled trial at 700, then another 30 open-label at 350 mg dose? We should hear about the 60 at 700 by the end of the year. Fingers crossed.
We simply need more data for comparison purposes, but so far, so good.
I'm pretty sure they are reporting fat content based on MRI-PDFF and fibrosis based on the MRI cT1 time, at least in the P2 DBPCT:
https://clinicaltrials.gov/ct2/show/NCT04521114
Assume that the open label portion, first N=5, used the same endpoints.
For comparing our results to others, we reported fat down ~5-45% and fibrosis down 0-10%. We can look at recent results from Phase 2 FXR agonist trials measuring the same thing, like from Metacrine:
https://www.globenewswire.com/news-release/20...grams.html
Mean Change (Baseline to Week 16)
Placebo (N=20) 3 mg (N=21) 6 mg (N=20)
Liver Fat Reduction (MRI-PDFF) % ±SD
-7.5% ± 21.0% -26.9% ± 27.8% -9.3% ± 55.8%
Median Liver Fat Reduction (MRI-PDFF) %
-1.5% -28.6% -26.9%
% of patients with >30% Liver Fat Reduction (MRI-PDFF)
11.8% 47.1% 35.3%
The above were actually pretty good results, with median ~25-30% reduction in liver fat content, 35-47% responders vs. 12% placebo, and good tolerability. However for other reasons, Metacrine canceled the program and the stock tanked just a few weeks ago.
It looks like 30% reduction predicts a good clinical response:
https://pubmed.ncbi.nlm.nih.gov/32882428/
Will need to do biopsies for Phase 3 (if our P2 results support going forward).
Lipocine had good Phase 2 results with their NASH drug, a testosterone precursor:
https://ir.lipocine.com/2021-08-25-Lipocines-...LiFT-Study
Their numbers aren't very clear "At 12 weeks, treatments with LPCN 1144 resulted in statistically significant liver fat reduction, assessed by MRI-PDFF, meeting the pre-specific primary endpoint of the LiFT clinical study. Statistically significant reduction in liver fat was observed compared to placebo: up to a mean of 9.2% absolute reduction and a 46.8% relative reduction in liver fat."
"up to"?
They got a FTD from FDA today based on these results.
Madrigal may be the leader in NASH with their resmilteon, with Phase 2 reported here:
https://www.sciencedirect.com/science/article...3619325176
They showed a mean 33% and 37% (12 and 36 weeks) reduction in fat content on MRI-PDFF compared to 10% for placebo. (Amazing in itself to think about how consistent is the placebo effect across NASH trials 10% - how does that work?).
They are hoping to file their NDA 2H 2022 and be first to market for NASH.
It's interesting yesterday's PR says N=90 now. I thought it was originally 50, then 60 (to get more biomarker data?), but now 90? So is it 60 in placebo-controlled trial at 700, then another 30 open-label at 350 mg dose? We should hear about the 60 at 700 by the end of the year. Fingers crossed.
We simply need more data for comparison purposes, but so far, so good.
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