genuine question about MASH that I am slightly embarrassed to ask
genuine question about MASH that I am slightly embarrassed to ask. I would rather ask a basic question now than get this wrong quietly for two months.
Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
Bought small because the evidence base is early. That is the only defensible position I could construct.
What this compound is actually being developed for, since the boards treat it as a weight-loss molecule with a footnote.
It is a dual GLP-1 and glucagon receptor agonist, and the glucagon arm links to hepatic fat and energy expenditure. The headline programme is metabolic liver disease, with endpoints scored on biopsy rather than on a scale.
That matters for how the data should be read. A histological response rate in a biopsy-confirmed population answers a very different question from a mean weight change in an obesity trial, and quoting one in place of the other — which happens in nearly every thread here — is not a comparison.
Tell me where this is wrong. That is the useful part of posting it.
best — the order this archive was captured in
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.
Is that a weight number from a different programme?
the titration in the trials was slow and deliberate
Which phase and which arm are you quoting?
Which endpoint — histological response, fibrosis improvement, or fat fraction?
I would not read across from the obesity programmes. Different population, different endpoint, different question.
phase 2 in liver disease is a different evidence question from weight
Yes — nothing containing this is approved anywhere, which is the first fact and usually the last one mentioned.
That figure is from the obesity programme, and this thread is about the hepatic one.
This. Biopsy-confirmed and imaging-suggested are different evidentiary categories and get run together constantly.
Agreed that the endpoint definitions matter enormously and almost nobody reads them before quoting a response rate.
Removed the escalation schedule. Unapproved compound, no protocols for other members, no exceptions.
MASH endpoints are histological, which is a much harder bar
biopsy-confirmed is not the same as imaging-suggested
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
Disagreeing with this bit: that number comes from a different programme with a different population.
Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use.
the weight numbers are secondary to what this is being developed for
Small fix — dual agonist, GLP-1 and glucagon. No GIP arm in this molecule.
Small fix — dual agonist, GLP-1 and glucagon.
Agreed — and the endpoint definitions are where the actual claim lives.
Are you reading the publication or a summary?
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
Biopsy-confirmed population or imaging-selected?
Correction: that is the imaging endpoint, not the histological one. The paper reports both and they differ substantially.
Has anyone posted an independent purity result for this compound?
- 1Agreed that the endpoint definitions matter enormously and almost nobody…6 comments in this branch · started by u/elin_tamm