Howdy. So a few thoughts. Viking clearly has their reasons for the doses they used. They have all kinds of data, the stuff I only dream about having. An important thing to consider is the plasma levels of the hip drug. The blood levels of the drug at the end of their 21 day trial were triple the levels they were initially seeing after dosing got going. My gut is telling me that this is a key factor in determining their dose range. This drug clearly accumulates in the body. Steroid molecules also stimulate secondary genetic pathways, and it's hard to argue 1:1 level to action effects when genetic signaling pathways are involved. The truth will come out soon enough if it was wise to go conservative on the dosing. This is a significantly longer trial, i.e. More time for the drug to accumulate. Who knows what the plasma levels will actually look like by day 90. Maybe they dosed conservatively to account for plasma accumulation. It could've been an error to jack the dose up too high, see huge accumulations with extended dosing period, and start to see some weird stuff. Based on the accumulation factor, I think they are doing it right. The plasma levels went up exponentially as the dose increased, so 2mg might not necessarily equal twice the concentrations of 1 mg. It's a shot in the dark. They are trying to get the sweet spot... high enough to show efficacy, not high enough to show side effects. There's literally no competition. Effect size doesn't have to be huge to get this in everyone's hands. It also needs to be mild enough to get it in everyone's hands though. Once you go too high in dosing and potentially show side effects, nobody will care that it occurred only at higher levels, it will be viewed equally as dangerous for all doses. And if the effect size isn't massive, it will stay on someone's shelf somewhere in that scenario. Bottom line, if they want this to be used in everyone that has a hip fracture, they have to minimize the risk of overdoing it. Keep in mind that it's a cool novelty to give people lower dose selective steroids after a hip... it's dr Frankenstein stuff to give bodybuilder doses of an anabolic pseudo-analog to grandma. They will get there. If they show good data and tolerability, the doses will eventually get jacked up in subsequent trials... but you gotta do that after everyone sees the safe little brother drug. The fact that he mentioned gastroenteritis as a side effect, when literally one person had it, makes me wonder if the piece is unbiased. It's an odd thing to mention in such a short article. But hey, it is mentioned in the trial report. I also smiled at the fact that he suspected they would be late to report, but hadn't realized they had already discussed the delay weeks ago. He doesn't appear to be actively following this, and he doesn't add anything new... it's a totally non scientific stock analysis. Another thought... they tested this drug in phase one in healthy 40/50 year old guys, people that already have higher muscle mass, steady jobs and routines... They weren't being put through strenuous physical therapy. They had nothing on the line healthwise to motivate them to boost strength. I expect these old hip patients to either sit in bed and wither, and maybe see some small muscle mass effect (they are using a wise approach with decades testing btw to find effect) or to hit the ground running and fight for their lives. I think that's why we are likely selectively recruiting. You just don't want the wither people, they clearly needed to find a model that selected them out. So if they are doing it right, it will probably be easier to see effect size and better results. There is more that can be implied along those lines, all of it good though.
Regarding his analysis of the lipid drug, he mentions that the reduction in triglycerides weren't statistically significant for the lower dose. That completely ignores the magnitude of reduction though. Tiny effect sizes in tiny populations with tiny p values... this is absolutely not the case. It just missed the p value cutoff, and likely only because of the trial size. They literally showed 75%+ triglyceride reduction at the highest dose, that's insane. The p value missed in the mid range on a nearly 40% triglyceride reduction. And he then gripes that they are using a 10 mg dose for the trials, and implies they aren't going to be analyzing triglycerides because he can't find it in the study brief on the FDA site. So he obviously did not listen to the conference call. If they didn't reduce the dose cutoff to 10 mg, who knows what on earth the new trial would have shown. It's one thing to reduce someone's triglycerides 80% if they have a severe hereditary disease associated with triglyceride accumulation. Reduce normal people with run of the mill high lipids, cutting their triglycerides by 80%... we have no idea what effect that would have on a common person metabolically. A lot of these pathways interact and have circuit breakers. Bodies do strange things sometimes to compensate. It's territory we don't need to be treading into. The study size for our phase two will easily meet p value if they powered it correctly, now that more patients are being studied. Again, it's the only sane way to be approaching the trial. I don't expect him to know that stuff, but I also don't expect him to be talking about p values and pretending to know what they translate to in terms of clinical significance, so I was disappointed in that regard.
Either way, in the world I was raised in, any press is good press. We are unknown. Even half hearted bash pieces, if negative, are still free advertising that we are out there. The more press we get before data, bad or not, the better positioned we will be to move on good data.
I also think he missed the mark on needing to dilute after results. He made no mention of their ATM arrangement, completely disregarded it. Yeah, dilution is possible... but it defies logic to see the company make it this far preserving insider ownership and utilizing less dilutive measures to operate, and to expect them to begin operating like every other crippled start up biotech.
He hit the mark though, with his target audience. If you know nothing about SARMs and lipids, you should stay out until they have data in hand. His advice to buy after news ignores the low float. My hope is that this will be a tough stock to chase on good news.
The article gave me a good excuse to review the old trials and data though! So not a total loss. I won't be losing any sleep over it though.
