RE:RE:Uphill battle in NASH for THOne thing to remember about NAFLD, not NASH, is that it is a pretty easy condition to reverse. I think I told that story here before, but about four years ago, after a CT-scan, my doctor told me that I had a fatty liver, in the following year, I lost 30 pounds, from 265 to 235. Then, after another CT-scan, the same doctor told me that my liver was back to normal. I am now at 230 pounds, and this spring I had another CT-scan and the same doctor told me I had no fat excess in my liver.
As I said before, I have a relatively serious chronic illness that I am treated and followed for. It contributed, before the diagnostic, to being slightly obese, at 265 my BMI was at 33, now at 230 my BMI is at 29, so not obese now, and I was midly obese then, and it was enough to have a fatty liver, and now my liver is normal with 13% weight loss. It is not the end of the world.
All that to say, that a patient in a trial that will change his eating and exercize habits can easily drop the fat content in his liver. In my my case I was not at the NASH stage, but still, for my doctor, on CT-scan, the change was obvious. Some patients could change their habits for a few months, but it is less likely they will do it for 18 months. In my case, having my illness diagnosed and treated helped me regain vitality and stamina, which allowed me to be physically more active, and on top of it, eating in a healtier way allowed me to lose the weight without a big effort and I am able to keep it that way now. So, all that to say that this NAFLD/NASH thing is tricky because it is closely related to how you eat and to physical activity, and if you feel better, the more likely you are to be more physically active. So to standardize that in a clinical trial is hard. NAFLD/NASH, like type 2 diabetes, is mostly a lifestyle condition. Bad food, bad eating habits, and being sedentary, and the more you gain weight, the harder it is to be physically active. It is a vicious circle.
jfm1330 wrote: Your analyst points out high placebo in non HIV, but it seems he does not take into account that HIV-NASH is likely harder to treat, so tesamorelin would be better in non HIV patients. Also, a critical aspect of the planned phase III is the 18 months of treatment. This will allow fundamental causes to be reversed to some extent, like epigenetic factors.
Epigenetic is a modified gene expression due to chronic biochemical abnormalities within a specific type of cell, in the case of NASH, liver cells, like too much fat accumulation or other modifications in the biomolecular environment. It likely takes time to reverse that with sustained fat reduction and other molecular modifications. 18 months is likely a key to achieve that. 18 months would also likely reduce the placebo effect since patients are more likely to settle back in their real eating and exercize habits.
SPCEO1 wrote: The following are comments on Egrifta in NASH from a US analyst. I would be interested to see if any among our medically competent group here would like to comment on his thoughts:
"I have seen their NAFLD data – the data is from a small trial in HIV patients with NAFLD – the MRI data is OK. True placebo in non HIV patients with NASH (not NAFLD) is like 15% which diminishes the effect there which makes me skeptical.
Also the question is what is the translatability of data from HIV patients with NAFLD to actual NASH patients? I don’t think we definitively know that and I am not sure they have data there.
Seems high risk to go straight into Ph3 NASH trial.
I have seen companies with better drugs and better data fail in NASH. It is a very tough space."
I think this is an overly harsh view of TH's data but it is nevertheless the standard view and the reason why the stock is not getting any respect for its NASH efforts. A few thoughts from a non-medical guy:
1.) MRI data - they had biopsy data so why is he focused on MRI data?
2.) I get the impression he may ahve only looked at one of Grinspoon's trials
3.) There were some NASH patients in the last Grinspoon trial if I recall cirrecctly, so it was not all NAFLD
4.) I thinnk AKRO had no placebo effect in their trial but their stock is still highly valued by Wall Street.
5.) While we don't know exactly how the data will translate from hiv to non-HIV patients, it seems fair to expect it to translate pretty well. I have to believe the tenedncy would be for Egrifta's impact to be better rather than worse on less difficult livers.
6.) While it is clearly high risk to go straight to phase III without the phase II data on non-HIV patients, can TH get a little respect for giving it a try or are we to conclude that Paul and his team are a bunch of kooks for doing so?
7.) Everyone has seen companies with better NASH data fail because, technically, TH does not have much, if any (depending on how you want to look at their data) on non-HIV NASH patients. And every drug has failed so far. So, I am not sure his last statement is worht much. I would have preferred he tell us a little more about why he thinks Egrifta is an inferior drug.
In the end, we can protest all we like but this does seem to be the prevailing view in the marketplace and is why TH is not given any value for its NASH program. Paul and his team need to understand this and provide analysts with a well-reasoned rebuttal.