RE:RE:This comment from LTF ay be of interest re: NGMI am not sure exactly what she was referring to but perhaps NGM was choosing a shorter time period in order to get results faster and spend less money but this blew up in their face since it likely takes longer for fibrosis to be halted or reversed. Alternatively, perhaps the way they set up the trial was to go for being the best drug in the space if the trial worked and bit off more than they could chew. Or it could be both that she was referring to.
qwerty22 wrote: Do you know what she means by "greed grab", I'm not getting the significance? Is she just talking about them rushing thru a short trial in order to get to the registrational trial backfiring on them?
I take her point that some detail of NGM's program might have worked against them. The short time of the trial maybe worked against the fibrosis endpoint. I can imagine a time component to all this. Fat deposition leads to toxic levels of fat, that triggers inflammation and cell damage/death, and in turn that triggers the scarring (fibrosis), that needs to happen in sequence. Treatment to reverse that still has to start with fat reduction, which in turn reduces inflammation which in turn stops the build up of fibrosis and then allows it's clearance. Reduction in fibrosis is the last step in the healing process and therefore takes time.
I imagine a simple small study where you start treating patients and then mri and fibroscan them every month to measure liver fat levels and fibrosis changes over time. In my simple model fat starts coming down at some point then there is a lag of x months a fibrosis comes down. I don't think anybody has ever tried to measure changes over time. Maybe that's not practical (I'm not suggesting any company does it) but it would be interesting to know the timing of this process.
SPCEO1 wrote: Good Morning Everyone, I want to chat a little bit about NGM. First, the two histological endpoints for pivotal Phase 3 NASH trials are- histological NASH resolution without worsening of liver fibrosis or histological improvement in liver fibrosis without worsening of NASH. Aldafermin was successful in the former endpoint but not the latter. The incovenient NASH truth is that NGM fell into the greed trap-this term denotes biiotech trying to achieve the more lucrative endpoint irrespective of what their investigative therapy is designed to do. Mechanistically, resmetirom/MDGL and aldafermin are similar in the sense that they are designed to alleviate fat accumulation with subsequent histological NASH resolution and "some" improvement in liver fibrosis. MDGL has consistently maintained histological NASH resolution as its primary endpoint-that remains the case for the pivotal Phase 3 trial in progress. So why did NGM deviate from an endpoint that is more feasible to mechanism of aldafermin to that which is not???? I don't have any specific answer to that question but it sounds like the greed trap. On release of the data, the usual culprits were blamed---the NASH patients. Based on FDA guidelines, this was a succsessful trial. I am left to ponder whether NGM proposed liver fibrosis to the FDA as the primary endpoint during the design of the trial ???--This is a logical conclusion which explains the abrupt discontinuation of aldafermin for NASH F2/F3 fibrosis. Look at column 4 and row 2 in first table denoting histological NASH resolution. Next, table 2-column 4 and row 1 on the robust liver fat reduction by aldafermin. You all know by now that I am not a fan of short treatment duration of 24 weeks ot less. An ideal treatment duration for NASH study should be 36 weeks and up. FYI, AKRO has followed the foodsteps of NGM/aldafermin-we know how that it will end unless revisions are made. In the absence of unforeseen error or safety signal-MDGL has the sizeable lucrative NASH therapeutics market on approval. This is where we are based on current events.