Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.
The manufacturing argument is the underrated one. Peptide synthesis capacity has been the binding constraint on this entire class, and a small molecule is made in ordinary chemical plants. If it holds up in phase 3, the supply and price picture changes more than the efficacy picture does.
Where I think it is weakest: the completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.
The narrow version of the question is whether a non-peptide oral agonist can match injectable exposure in practice, or whether the convenience is bought with a lower ceiling. I have searched first, so if this is covered somewhere point me at it and I will read it.
MASHdoc_SA said:The manufacturing argument is the underrated one.
Agreed, and ALT falling is not the same as fibrosis improving. Enzymes are a crude proxy; FIB-4 or elastography is what tells you about the thing that matters.
MASHdoc_SA said:The manufacturing argument is the underrated one.
Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. Small molecule does not automatically mean cheap. Price is set by what the market will bear and by patent life, not by cost of goods, and I would not assume the savings reach patients.
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View ResultsAnswering the narrow version, because the broad one does not have a single answer. Orforglipron is a small molecule rather than a peptide, which is the whole point: no SNAC absorption enhancer, no fasting window, no cold chain, and oral bioavailability in the tens of percent instead of around one. Phase 2 put it near 14.7% weight loss at 36 weeks on the top dose with a side-effect profile that looks like the injectables.
NurseKim_ATL said:Agreed, and ALT falling is not the same as fibrosis improving.
This matches mine closely enough to be worth saying so out loud. Posting only so the count is not one.