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TOCA
SLS - a lot of strange things in that PR, among them:
1) DSMB gives out results for a blinded trial, albeit single blinded, at interim despite not being stat sig overall
2) my guess is the non- picked subgroups (ie hormone treated and not TNBC) probably had an HR meaningfully above 1. If so this implies the HR seen in the subgroups is suspect.
3) The company announced complete enrollment of 300 people in Sept, but the PR was only for 275. Where did the other 25 go?
4) why does the relative risk reduction not equal 1-HR?
5) and just a reminder that this is a GALE drug and a GALE trial.
SGEN
TOCA
Ok - the bear case:
a) This was 6 CRs in a subgroup of the resection subgroup of phase 1 (which was, in total, 127 patients). And parts of that subgroup look *very* post hoc (e.g. no prior Avastin in rAA or rGBM). All told, based upon nothing more than that I would suggest that the ph3 results won't look anywhere near as good as the 20% they are claiming.
b) Survival after glioblastoma surgery is a significant function of how much tumor can be removed, and part of the subgroup is about tumor size - i.e. a very good surgeon and associated team can probably significantly boost survival.
b) The OS of the high dose vs low dose populations of this same subgroup are not particularly compelling.
c) They are silent on the other subgroups of the ph 1. Any PRs? My guess is not, or they would have said so.
My guess is that, as with many drugs, it works but works only weakly and/or in a subgroup that is difficult to find.
RTRX -
CCXI Renal Drug -
In renal failure there are 3 primary things that matter:
a) Proteinurea - this is by far the easiest to measure and to drug, but the prognostic values (as a drug efficacy biomarker) is extremely suspect. It is a measure of how much your kidneys are leaking.
b) GFR (or eGFR) - this is harder to change, but is often the primary way in which it is decided whether to start dialysis. It is also a measure of how much your kidneys are unable to pump out toxins (i.e. a measure of how miserable you feel).
c) Hyperkalemia - this is generally an acute reaction to insult. E.g. the ACEs and ARBs, which are SOC for renal drugs, create a spike in the population of hyperkalemia events. But note that because the decision on whether to start dialysis is very non-standardized, many patients start permanent (instead of temporary) dialysis at a hyperkalemia event.
As for FSGS (and CCXI) - multiple companies are now pursuing FSGS because it is the most proteinuric of the renal diseases and their drugs seem to 'treat' the proteinurea. But it far from clear that this provides long term clinical benefit since they may provide no benefit in GFR (as CCXI didn't in their DN RCT) or harm GFR.
IFRX - Thanks Jim. Will be interesting to see if they include Ada arm (50/50 IMO).
Question: Do you know why the complement sector of biotech seems to overwhelmingly focus on non-inflammatory diseases. E.g. IFRX initially focused on sepsis, others on GVHD, ... . This has struck me as odd since I've watched it - but there must be some reason for it, albeit perhaps just a historical one.
IFRX - have you seen a good description of their planned ph2? E.g. Against ada or placebo, and the number/size/treatment of the different arms? (The answers they gave in the Leerink cc imply that they will explore every other week dosing, but beyond that...?)
TIA
VKTX - thanks for the link to the definition of "Elevated Liver Enzymes" that they used in their trial. (It's clear from their material it wasn't the normal >3xULN, but hadn't yet found what they did use.) However I would suggest that there is still a significant risk since, as I noted before, the elevated bilirubin also shows up in the same dose cohorts.
That said, difficult to fully compare MDGL and VKTX since they aren't releasing fully comparable data. E.g. What is VKTX average liver enzyme change at each dose? Possible, although unlikely (because companies always tout good results), that average liver enzymes went down at lower doses.
VKTX
Limits of biotech/biopharma growth? This article made a big splash about a month ago, which puzzled me at the time since it provided unclear theses, some questionable assumptions, and poor extrapolation of data. Normally I would write a short post detailing the failings of the article, but since I think the topic is worthy of (clearer) discussion I waited until I had time available to do a more thorough job.
Article's thesis:
Here is the thesis that it initially propounds:
SRPT
SRPT
DBVT
Weirdest, or most annoying, biotech website I have ever seen.
Iwfal should like that article---the IONis connection.
I guess I'm just biased against..engineers...I should know..SB..Chem E. MIT...I can not think of anything I learned in Chem E that would help me in clinical research...What I have noticed is that MDs try to bring engineering concepts into medicine...
Me: Q: if the same AE shows up in 3/4 of trials, but is stat sig in none, do you dismiss it? A: absolutely not. It is probably real.
You: Why? If not stat sig, means results were random, could have occurred by chance - just because multiple trials (likely with huge differences in trial design and patient population) might show what appears to be a pattern, that does not mean the pattern is real. You could probably find other invalid patterns if you dug deep enough.
Figure 3. I'm waiting
"As for Jelis, you mean that trial where the treatment arm had more deaths than the placebo arm? (Did I get that right wink.)"
Nope...Sounds like you are using Pyrr for your source...
Awful, do you mean to say 90% of us using it off label should be experiencing bleeding? I must have rock gut then after taking Vascepa for the last 3+ years.
"As for Jelis, you mean that trial where the treatment arm had more deaths than the placebo arm? (Did I get that right wink.)"
Nope...Sounds like you are using Pyrr for your source...