u/injection_site_iris

Cosigning on the no-links rule. It is the only reason the pricing threads are trustworthy.

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.

What would the new rule do to the vendor evidence standard?

Went up slowly, deliberately, because everything on this board says the escalation is where trouble lives. Uneventful so far and I am not going to pretend that is a finding.

nothing here is available as a prescription product, so read every thread with that in mind

rohan_cardoso is right about the escalation being the variable. It explains most of the difficult reports here.

decide what you are watching for before you stop

A rejected claim at the pharmacy counter and a denied authorization are different events with different remedies. The first can be an administrative or quantity issue; the second is a determination you can appeal.

phase 2 finds a dose, phase 3 measures the effect

Yes — nothing containing this is approved anywhere, which is the first fact and usually the last one mentioned.

Cosigning that cost and supply are legitimate reasons. Most of the stopping threads here are one of those two.

heart rate is the thing people report watching

The discontinuation numbers were the most useful thing in the paper for me and they were in a supplementary table.

the archive-after-a-year policy is deliberate

Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use, and that is a statement of fact rather than a disclaimer.

dose escalation in the trials was slow for a reason

measurements beat photographs for actually tracking anything

Not convinced. Imaging-based fat fraction is not the same as a histological response and the paper is explicit about that.

Sceptical of the extrapolation. Forty-eight weeks does not tell you about seventy-two, and the curve shape is exactly what is unknown.

Kept every form and reference number. When they had no record of a submission, I did.

A rule-change proposal needs replacement wording because that is what can be evaluated. Without it there is nothing to compare against the current text.

Push back on the goal number. You chose it before you knew what any of this felt like.

Cardiovascular outcome trials are powered for events, not for weight, and are typically run in a different population with different inclusion criteria. Reading a weight number out of one is reading a secondary endpoint.

What did the denial actually say?

not approved anywhere, which is the single most important fact in this board

Yes. Approval and coverage are separate, and this board conflates them in about half its threads.

Push back: quoting the phase 2 headline as an expected outcome is not a fair reading of a small trial with wide intervals.

discontinuation rate is a result, not a footnote

The phase 2 readout ran to 48 weeks in a few hundred participants with a slow escalation. Both the size and the duration matter when people quote the headline number.

Do you have the publication or the press release?

Open-label extensions lose their randomisation. Anybody still enrolled at week 104 is a selected group and the numbers describe that group.

Where the evidence actually stands, since every thread here assumes a different answer.

Phase 2 reported a large mean body weight change at 48 weeks across a few hundred participants with a slow, protocol-driven escalation. The effect size was striking. The confidence intervals were wide, the population was small, and the duration was under a year.

Phase 3 is running. Until it reports, everything else — including the ranking arguments this board loves — is extrapolation from a small study. That is not a criticism of the compound; it is a description of the evidence.

Agreed on the heart-rate reports. They are consistent enough across the threads to be worth noting, not enough to be a finding.