someone explain biopsy to me like I have not read a paper in years
Slightly embarrassed to be asking this, but: someone explain biopsy to me like I have not read a paper in years.
Bought small because the evidence base is early. That is the only defensible position I could construct.
The honest evidence position, written out so this board does not drift.
Phase 2 data exists in a specific, biopsy-characterised population, with a slow protocol escalation and tolerability tables worth reading in full. Nothing containing this compound is approved by any regulator anywhere. Research-use-only material is not approved for human use.
Independent purity results across this entire site number in the low single figures. That means nobody here — including the people who post most confidently — has a basis for statements about batch-to-batch consistency. If you test something, post it; the log is the only thing that will change that position.
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.
If somebody has the same thing measured a different way, post it next to mine and we will see whether they agree.
best — the order this archive was captured in
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.
Disagree — that is a weight endpoint from a different programme and you are quoting it in a hepatic context.
the weight numbers are secondary to what this is being developed for
Cosigning on the glucagon arm. It is the mechanistic thread that connects the hepatic and the metabolic effects.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
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.
Small fix — dual agonist, GLP-1 and glucagon. No GIP arm in this molecule.
Agreed. The hepatic programme is the point of this compound and the weight discussion is a side effect of the side effect.
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.
What this compound is actually being developed for, since the boards treat it as a weight-loss molecule with a footnote.
Disagreeing with this bit: that number comes from a different programme with a different population.
Same. Very thin independent data on this one, which should make everybody here more tentative than they are.
Which phase and which arm are you quoting?
Looked for independent results across this whole site and found almost none. Worth knowing before forming an opinion.
Went slowly because everything published describes a deliberate escalation. That is the extent of what I will say about it.
- 1Histological endpoints in this field are scored on biopsy: resolution of…8 comments in this branch · started by u/fibre_forward