Spectrum Pharmaceutecals Inc (SPPI)

[antihama]

Hi spiderman, been away and just starting to get caught up regarding this abstract and the quarterly CC (Read the transcript quickly but would like to listen to the CC). Regarding this abstract, there's some interesting stuff and some strangeness to it. Definitely, Dr Socinski should have had this QC'd by Quality before releasing it. For instance

Patient pharmacokinetics demonstrated a dose-proportional increase in plasma (half-life of 7.9 hr at 16 mg QD) with and no accumulation.

Ignoring the 'with', a word that just seems to be out there by itself, a t1/2 of 7.9hr begs the Q wouldn't twice a day dosing be better. And they really don't know if there is "no accumulation". What they do know is that after doing a blood draw, and analyzing for pozi, it's not in the blood circulation. But the circulatory system is just one reservoir where pozi can accumulate. It's possible it can accumulate in other reservoirs such as the liver, kidney, etc and the only way to know that is from a dissection. They can get this from a pre-clinical animal ADME study but not from this trial. They could also do a very early in man trial of pozi w a radioactive isotope (such as tritium or carbon) where the patients pee, poop and breathing is captured and if they get near a 100% capture of radioactive material infer no accumulation but they need to explain it at the meeting. So maybe I'm being picayune about it but perhaps they should have said "no accumulation in the circulatory system". Maybe pozi is accumulating in another organ and is causing AEs?

And what does "ORR was achieved if the 95% CI>17% in the ITT Population" mean? Shouldn't it say the ORR was 15% (95% CI 13,17%) or something like that. So if they're saying "ORR was achieved if the 95% CI>17% in the ITT Population" are they saying that the ORR bar (or benchmark) was 17%? I'm not sure. I guess we'll need to listen to the upcoming CC to find out.

Impact of drug compliance/holidays coupled with its short half-life due to AEs may have reduced efficacy

The short half-life is due to AEs? Huh? Come again. Maybe they need to hire better PK scientists. It's not the short half life that is causing AEs but a high Cmax (ie maximum concentration) that would cause the AEs. Shish! That's basic pharmacokinetics. However, what I think they are trying to say is that a reduced dose at more than once a day would be much more effective. It's disappointing they are finding this out now. I don't know how MDACC was able to keep patients on trial longer. They still need to explain why MDACC was able to keep patients on their trial longer (we assume) than in the Z20 trial.

Lastly, the following statement is interesting

Studies to optimize dose and schedule for ongoing and future studies are in progress

I've expressed previously that I don't think Z20 cohort 2 will be SS. And I've expressed hope that cohorts 3 and 4 may be positive due to possibly keeping patients on trial longer where pozi can work its uninterrupted magic because they are healthier and less impacted by AEs (total speculation). We know they still are recruiting patients for cohorts 3 and 4 (mostly 4) so maybe they can implement some of the learnings w the remaining patients by making them understand that the longer you stay on trial the better the outcome.