small win: MASH stopped being a problem at week 43
small win: MASH stopped being a problem at week 43. Full detail below, and I have tried to keep the editorialising out of it.
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
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.
If two or three other people have done the same thing we might actually learn something. Alone it is an anecdote.
best — the order this archive was captured in
Independent result logged. There are almost none for this compound, so it is genuinely valuable.
Agreed that the endpoint definitions matter enormously and almost nobody reads them before quoting a response rate.
Correction: that is the imaging endpoint, not the histological one. The paper reports both and they differ substantially.
Agreed that the endpoint definitions matter enormously and almost nobody reads them before quoting a response rate.
Agreed — and the endpoint definitions are where the actual claim lives.
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost no
Disagreeing with this bit: that number comes from a different programme with a different population.
Disagreeing with this bit: that number comes from a different programme with a different population.
joaquin_ivaturi is right that biopsy and imaging endpoints are not interchangeable.
Small fix — dual agonist, GLP-1 and glucagon. No GIP arm in this molecule.
It is a dual agonist at the GLP-1 and glucagon receptors. The glucagon arm is associated with increased energy expenditure and with effects on hepatic fat, which is why the development programme is oriented towards liver disease.
Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use.
This. Biopsy-confirmed and imaging-suggested are different evidentiary categories and get run together constantly.
That is an escalation schedule for an unapproved compound and this board does not host those.
Yes — histological endpoints are a far harder bar than the surrogate measures people are used to quoting.
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.
the titration in the trials was slow and deliberate
Sent a vial to PeptideMeter because there was nothing on file. 99.3% against a claimed 99.0%. First entry for this compound in my own log.
Disagree — that is a weight endpoint from a different programme and you are quoting it in a hepatic context.
Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
Is that a weight number from a different programme?
Which phase and which arm are you quoting?
The endpoint vocabulary, because you cannot read this literature without it.
Resolution of steatohepatitis without worsening of fibrosis and improvement in fibrosis without worsening of steatohepatitis are the two standard composite endpoints, both scored on biopsy by pathologists against a defined system. Liver fat fraction is an imaging surrogate that correlates imperfectly with histology.
A trial can move the surrogate substantially and the histological endpoint modestly. Both results are real; they answer different questions. Anybody quoting a response rate here should say which endpoint it refers to, and most summaries do not.
The escalation schedules in the published protocols are slow and deliberate, and the tolerability tables show why. That is a description of the trials rather than a suggestion for anybody.
glucagon agonism and energy expenditure is the mechanistic thread
- 1Independent result logged. There are almost none for this compound, so it is…7 comments in this branch · started by u/liver_enzyme_liz
- 2Independent purity results for this compound are very sparse across the…7 comments in this branch · started by u/incretin_ivy