[Question] how do you actually verify MASH
how do you actually verify MASH. I would rather ask a basic question now than get this wrong quietly for two months.
Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
Sent a vial to Janoshik because there was nothing on file. 99.1% against a claimed 98.5%. First entry for this compound in my own log.
Looked for independent results across this whole site and found almost none. Worth knowing before forming an opinion.
Ask me anything specific. Anything general I will probably get wrong.
best — the order this archive was captured in
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.
Left up. It reads the paper carefully and is explicit about the population.
That figure is from the obesity programme, and this thread is about the hepatic one.
this board is small because the compound is early
Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
Small fix — dual agonist, GLP-1 and glucagon. No GIP arm in this molecule.
Spent an evening on the histology scoring system and understood the trial literature far better afterwards.
Is that a weight number from a different programme?
Bought small because the evidence base is early. That is the only defensible position I could construct.
Bought small because the evidence base is early.
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.
Went slowly because everything published describes a deliberate escalation. That is the extent of what I will say about it.
read the histology endpoint definitions before quoting a response rate
a liver endpoint is not a weight endpoint with better marketing
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.