i am putting here my opinion regarding AUPH
1) first things first, SAFETY , incredibly huge endorsement for the use of the drug. we have 2 options here:
1.1) the 5 death in the Placebo were caused by worsening SLE disease and in this case this is huge for AUPH because we proved we were able to limit the disease worsening with VCS
1.2) the 5 deaths in Placebo were caused by AEs and in this case there is no points for us since it could have been the other way around if those patients were in the VCS arm ( it happened in AURA).
so Either way we have proved we are as safe as SoC and even we could have saved life if 1.1) is the case
2) Delta is 18.5% but the real delta should be around 25%. why:
If you look at the 24 week results you see that we had the same numbers as AURA at 24 weeks (32% VCS vs 19% Placebo) so the difference happened between week 24 and 52. what changed here can be explained through 2 scenarios:
2.1) A major criteria which is the increase of steroid dose prohibition, shifted from week 16-24 in AURA to 44-52 in AURORA , this means you can't adjust the steroid dose during these final weeks for patients showing a relapse ( it was one of my main concerns in my previous posts and i suspected that the 100% rate of those who stayed in CR between 24 and 48 weeks will not be met in AURORA).
BUT, in real treatment conditions this is not something that will happen , the 44-52 weeks criteria is only for the trial only , in real conditions a physician will adjust the steroid dose to put a relapsed patient back in a CR condition (as long as he has responded initially to the drug) so basically we really should see the AURA % which was 49%
2.2) the difference of 8% between week 24 and 52 instead of 16% as in AURA was due to patients who were in CR at 24 weeks but quit due to AEs (and this happened in AURION 2 out of 7 left due to pneumonia and high fever when they had CR). Again, in real life this is treatable, the patient will not quit a treatment for AEs if he is responding to the treatment, there are a lot of ways to treat him to put him back on track, so the real CR rate should also be 49%
all this to say that the real Delta is 25% as AURA because the most important parameter is CR at 24 weeks (same as AURA) and the total responders (70% same as AURA). those responders at some point will turn into CR.
so when you account for all those exceptions, you see that we are not far off from where AURA results were except that we have a better safety proof. the only thing that remains now is the long term Nephrotoxicity impact because this will define if VCS will be a chronic treatment ( valuation over $50)or a temporary one. so far, all the signs point that we don't have a long term Toxic effect (eGFR levels go back to baseline levels after trial finish) and even the side effects (lipid, glucose, high blood pressure) were not encountered ( the TG and cholesterol went down actually as per Neil in the CC).
a quick comparison to Roche drug, we are way better since our response is way faster ( Roche had the CR rate of 24% same as placebo at 24 weeks and we have 32.5%). our CR is attained in 7 weeks when it is in 12 weeks on average with placebo and Roche). the Speed of remission matters a lot to physicians so we are the best in this domain ,and by far imo.
Full disclosure, i am holding to all of my shares because this has just started, give experts some time to realize the full potential especially when they start publishing the data in conferences.
GL all
