reading MASH threads from 2024 and half of it aged badly
reading MASH threads from 2024 and half of it aged badly. It is the sort of thing everyone half-believes and nobody writes down.
Histological endpoints in this field are scored on biopsy: resolution of steatohepatitis without worsening of fibrosis, or improvement in fibrosis without worsening of steatohepatitis. Both are harder to achieve and to interpret than an imaging surrogate.
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
Phase 2 in a biopsy-confirmed population is a demanding design: recruitment is slow, the population is specific, and the results do not generalise to people who have not been characterised that way.
Research-use-only material is not approved for human use and nothing here should be read as a recommendation to use it.
best — the order this archive was captured in
Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use.
Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
biopsy-confirmed is not the same as imaging-suggested
research material is not approved for human use, which is why the clinical record here is thin
read the histology endpoint definitions before quoting a response rate
the hepatic data is what makes this compound different from the others
Careful with the mechanism claim. Glucagon agonism is plausible as an explanation and it has not been isolated as the operative one.
Push back: the evidence here is phase 2, in a specific population, and it does not support a general ranking.
Retitled to name the endpoint. Histological and imaging results are not interchangeable and the original title implied they were.
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independent testing on this compound is very thin
Correction: that is the imaging endpoint, not the histological one. The paper reports both and they differ substantially.
glucagon agonism and energy expenditure is the mechanistic thread
That figure is from the obesity programme, and this thread is about the hepatic one.
That figure is from the obesity programme, and this thread is about the hepatic one.
Agreed — and the endpoint definitions are where the actual claim lives.
Looked for independent results across this whole site and found almost none. Worth knowing before forming an opinion.
a liver endpoint is not a weight endpoint with better marketing
Correcting myself: the readout I quoted was the 45-week interim rather than the endpoint.
Right, and the trial titration was slow for reasons that are visible in the tolerability tables.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
Agreed. The hepatic programme is the point of this compound and the weight discussion is a side effect of the side effect.
not approved anywhere, and the boards forget that constantly
- 1Push back: the evidence here is phase 2, in a specific population, and it…9 comments in this branch · started by u/sofia_danquah
- 2Looked for independent results across this whole site and found almost none.…7 comments in this branch · started by u/employer_carveout