Greetings... haven’t been on here much. All this stuff is just my own guesses and opinions (standard disclaimer!), as always please do your own DD. So there truly isn’t a lot put out by Viking on the ALT stuff, nor have they ever indicated a need to put out more. They seemed satisfied to cut max dose, and to express that ALT was only thing involved, and really never got (or stayed) That much elevated. The trial was phase 1, 14 days of dosing, and they saw the mean (add all the ALT levels together and divide up and get an average) - so a mean increase in ALT levels that was dose dependent. Imho not a limiting thing based on the data available, based on the limited stuff they had from 14 days of dosing. So the more they gave, the higher the average ALT. They said the highest was in the 40 mg dosing (not being used in phase 2), ALT only (no mention that AST or alk phos or bili going up) with the highest being ALT of 1.5 times the ULN (upper limit of normal) in the 40 mg group. They don’t say if 1.5x ULN was the average they got in that group, or the highest they saw. I’m assuming it may have been highest seen, but unsure on that one, and neither to me is really that scary at this time while waiting on much better and longer data sets.
I could talk about this stuff for a really long time from a lot of angles, but it’s just too hard to guess. A lot of drugs that do stuff involving the liver can transiently (briefly) raise LFT’s... which makes us look closely and make sure it’s not getting out of control. A good example would be Hepatitis C treatment drugs. We know that our drug likely shall (continue to) provide massive lowering of liver fat, really quickly (based on only 14 days of dosing the results were substantial in lowering fat in that same ph 1 trial).
I could provide a lot of analogies on like was it too much too fast and the mechanism involved is contributing vs other pathophys angles, or is it necessarily an awful thing in clinical context, etc, but who knows at this time. Either way, they likely realized they didn’t need that huge of a dose based on how well it worked after 14 days, and was overkill. So the doses they subsequently picked seemed reasonable for ph 2. Is it something where LFT’s will naturally normalize regardless as the fat burden resolves and ongoing inflammation ebbs, who knows. Is it likely to cause ongoing damage after the drug is gone... that would be really unexpected based on what we know and other data etc, but that’s why the post dosing monitoring period with the phase 2 is so helpful with our current ph 2. So in our case, it’s this weird thing where we have a drug that we originally found to do something really really well... and phase 2 becomes just as much about finding the sweet spot dose, and assessing longer term tolerability. 1.5 times the upper limit of normal ALT-only (there are several liver markers) elevations at highest dosing with overkill efficacy would surprise me if it kept us from market, but anything is possible if new stuff is revealed, so it’s not like some 100% guaranteed nothing... no drug ever is at this stage of course. And I’m not bragging here in saying that our drug seems to be more potent and effective vs MDGL based on phase 1’s. If we jacked up the MDGL dose to huge comparative levels to hit a 40 mg equivalent dose of 2809, would we see LFT increase similarly... as a betting man, I’d say there’s a reasonable chance. Several things could make it not happen, but beyond the scope.
Anyways, they didn’t terminate the current trial early... and dosing is being finished. This seems to suggest to my betting man’s brain that there was less likely to be found some cumulative additive dose ALT thing. That’s the type of thing that leads trials to be altered and higher dose arms to be eliminated. So yeah, we may see a transient something etc, or may see it briefly and then gone, or whatever.
I am typing on my phone (as usual), and really hate going into long winded wild scenario guesses and postulations and spelling it all out in this format. So I guess I will just give you my short story version. I’m willing to continue my bet based upon all the scenarios I can create, and the MDGL competition implications. Even if stuff was there, I still think it will place an equal amount of scrutiny on MDGL... and end up in both of our drugs getting to phase 3’s based on what I continue to view as a reasonable and likely tolerable risk benefit setup. If our stuff shows more ALT stuff than before, or a longer term dosing concern, the FDA might make MDGL do a higher dosing arm or put them through more scrutiny too, it’s not like we have to automatically lose, if you get my drift. It would be hard for this stuff, if still there, with a trial that has been allowed to complete, to sink us at a phase 2 to phase 3 transition point. Buyer beware, anything’s possible. My bet is that this trial, if it shows even identical profile to phase 1... which was pretty great in My Opinion, will get us to phase 3. Now anything’s possible. When u talk transplants and no effective available treatments at the moment, the talk is generally about SAE’s, that would keep us from phase 3.
If you have specific what-if scenarios, I don’t mind delving deeper, but I don’t want to overwhelm with 20 different what-ifs. Once we get the actual data, I will explain a lot more, and really hash out clinical implication possibilities, if the need arises. So I guess I can only say that I am holding, and I personally find this situation a tolerable unknown for me, based on my working knowledge and the risks benefits we currently know.
If you google the list of FDA approved drugs that require liver cautions and monitoring, it would blow your mind. It’s impossible to keep up with clinically, and growing all the time... internet drug interaction checkers and monitoring recc guidance checkers are the new norm in medicine, for reasons like this... not fda denials. Denials lately have been reserved for toxic drugs and drugs with proveable and unavoidable pathophys flaws that make them worse than getting no treatment, or the current standard. The current standard remains... no available treatments, and the nash market seems to be growing by the day, given our country’s fast food lovin ways. The 3 month follow-up data is really what I’ll care about, and seeing how quickly the ALT normalizes. Statins are pretty nasty drugs imho, we aren’t competing against angels, nash aside. In fact, I think that we are most appealing in buyout situations to statin makers. Statins are going the way of the dinosaur lately, losing their luster imho. Having a statin alternative with a potentially tolerable side effect profile would boost any of the statins existing marketing channels and shoot some steroids (sarms lol- joke!) into what is quickly becoming a difficult marketing dept for a lot of these companies that are unable to differentiate themselves... let alone the combo drug combinations they could potentially one day spin off to make their toxic statins more palatable to currently weary patients and doctors.
To all the longs, friends, fellow Vikings, hope all is well. What a ride! I’m still clutching tightly to most of my position. We may be rowing to Valhalla in a few months. And Greens... dang... your passion for this company... there was once a time when $10 seemed an impossible dream lol. Now I don’t think I’ll be happy with anything under ___ ??? (who the heck knows). Mostly posting out of respect to longs, and to let all my countrymen know that money hasn’t changed my passion for this company and what we may someday (soon) show the world.
Cheers brothers. I’m moving to Denver next week and have been more than preoccupied with moving etc etc. If data is what I suspect it may be, perhaps... by 2019, a celebration may be in order. Take care all, wishing everyone the very best in life
AI
