NGM 282: Phase 2 trial results

General
1

Another fairly positive PSC clinical trial report…

“Effect of NGM282, a FGF19 analogue, in Primary Sclerosing Cholangitis: a Multicentre, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial”

Highlights

  • •NGM282 is a first-in-class, engineered analogue of the endocrine hormone FGF19.
  • •Administration of NGM282 did not significantly affect alkaline phosphatase levels in patients with primary sclerosing cholangitis.
  • •However, NGM282 significantly inhibited bile acid synthesis and improved serum markers of fibrogenesis and liver injury.
  • •These findings challenge the dogma about what the appropriate endpoints should be for trials in PSC.

https://www.journal-of-hepatology.eu/article/S0■■■■(18)32519-4/fulltext

2 Likes
2

Without long-term survival data, this result does not challenge the dogma, if that means the use of ALP as a predicting factor for PSC prognosis. I hope they have follow-up study on those patients. That last statement is purely academic argument.
But I’m always curious about the role of ALP in PSC since it’s originated from multiple sources in GI system.

3

My understanding is that ALP is not very good predictor in PSC eg as seen in Urso that improves ALP but does not seem to affect long term outcome.
I know there has been lots of analysis what factors should be used in clinical trials to measure effectiveness. No consensus exist yet…

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Did those Urso-responders have better prognosis when compared to non-responders? That’s why they still let those take Urso. That’s my impression. Don’t have that paper right now.

5

Yeah, I found one Urso paper from 2011 that concludes
“ Eighty-seven patients met the inclusion criteria. Normalization of alkaline phosphatase was seen in 35 (40%) patients. Five (14%) patients with normalization reached an end point whereas 17 (33%) of the patients with persistent elevation reached an end point ( P =0.02). Ursodeoxycholic acid was used similarly by both groups.”

So 14% vs 17% so it did help…at least in few cases…

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no, that’s 14% vs 33%, quite significant difference.

7

Oh my bad
Yes, seems indeed that ALP has reasonable predictive value