Amazing that BP just keeps going after the failed amyloid plaque hypothesis, time after time, after time. Meanwhile, article after article in academic journals keeps adding to support for the Anavex approach via the Sigma-1 receptor and for the general hypothesis that Alzheimer's stems from a confluence of factors -- inflammation, oxidative stress, mitochrondrial dysfunction, calcium imbalance, etc.
Nothing else has even come close to the data Anavex has shown. The other high-profile attempts were just trying to help with symptoms: Biogen, Lilly, Prana, Roche, Axovant, etc. It's a graveyard. They all (except Prana) just keep beating their heads against the failed amyloid-plaque hypothesis.
With Anavex, we have significant improvement seen in all four trial measures: MMSE, ERP, Cogstate, and ADCS-ADL. Despite the trial not being powered for stat sig, 2-73 was so effective that it achieved stat sig anyway in several ERP and Cogstate measures. Then the dose-response PK/PD analysis showed a stat sig relationship between dosage level of 2-73 and degree of improvement in MMSE and ERP, debunking the arguments of placebo effect (would have been one heck of an unprecedented placebo effect!). Most impressive of all, the interim 12-wk data showed 11 of 14 patients improving their ADCS-ADL scores by a mean/median 3.21 points. No other drug has ever even come close to that kind of impact in the ADCS-ADL measure.
But I'm sure it was just an accident that patients and caregivers clamored for a two-year extension on 2-73 and that we are hearing about patients re-learning to play piano, paint, play golf, remembering how a granddaughter takes her coffee, how to get to the mall by themselves, and so on.
Nah, I'm sure all this is just a coincidence, right? I mean, why even bother developing drugs when the placebo effect is this effective? OK, so the placebo effect has never before achieved anything close to this kind of data in previous Alzheimer's trials, granted. But there's a first time for everything, right? Heck, maybe the placebo effect or a strong cup of coffee could even make me dunk like Michael Jordan. That'd be sweet.
Absolutely, lots to anticipate. I follow a lot of small bios and Anavex has really impressed me over the last year how quickly it's moving on all this, surpassing all my others (some of which it was pretty far behind two years ago).
Preach! I agree. We get data at AAIC in late July, the first major scientific conference for AD since Barcelona (where the company gave five-week data).
As we already know from interim ADCS-ADL data, it will be good. I'm holding my core forever -- wanna get that REGN-type payoff! Helping support a company that can actually do something against Alzheimer's is a pretty great incentive as well. The life you save may be your own, as F O'C would say.
Exactly. The last major scientific conference for Alzheimer's was Barcelona where week five data was released. The next major scientific conference for Alzheimer's is AAIC in late July, and that is where twelve week data will be released, not just efficacy data, but PK/PD data as well, which is the part that has taken so long to analyze: for week five, efficacy and PK/PD were released separately, with PK/PD coming out two months later. This time they are waiting for PK/PD data as well (and for the major platform that AAIC provides) so that there can be no credible complaints of placebo effect when the efficacy data is good, as we know it will be from the interim 12-week results for ADCS-ADL that were already released back in November.
I agree that he could have been clearer from the outset, and even now, that this time they would wait for PK/PD analysis before releasing efficacy data.
PK/PD data does still take months to crunch, though, even with modern state-of-the-art software (NONMEM being the gold standard). That is why five-week PK/PD data came out two months after the five-week safety and efficacy data, and why this twelve-week data release is taking so much longer, because this time they want to release efficacy and PK/PD data together.
Also, we already know from back in November that the 12-week data will be good, no matter when it comes. In that interim 12-wk data release, 11 of 14 patients improved their ADCS-ADL scores, with a mean/median (not sure which) improvement of over three points. That degree of improvement in ADCS-ADL has never before been seen in an Alzheimer's trial.
So no matter when the full release comes, even from that alone (in the unlikely event that the other measures somehow reverse their positive trend at wk 5), we already know the 12-wk data will be excellent.
AVXL management already has funding in place via the LPC deal. A good BP partnership would be better, but is not essential at this time. Anavex can do the Phase 2/3 trial with the LPC money if necessary.
I know you are long, but you are wrong that nobody talks about financing. The bashers in particular make sure we discuss financing plenty.
Anavex can run a Ph2/3 trial with the Lincoln Park deal if no acceptable BP partnership emerges at this time. What is laughable about that? The toxic financing that supposedly must be a part of any Lincoln Park deal is nowhere to be found in this deal (no warrants, etc). That is the advantage to hiring a top-notch law firm like K&L Gates and having good trial data (unlike most other small biotech companies that LPC deals with).
Given that the Ph2/3 will be enrolling about 300 patients rather than the 1000 that many associate with Ph3 trials, $50M (taken along with their present $12M or so, plus more from the remaining warrants) will be plenty to run the trial. Then if necessary they can do another deal with Lincoln Park.
Looks like an overview sort of conference to me and therefore I think Missling will give an overview rather than new data, but I'm open to surprises. We already know the data will be good when it comes (thanks to the interim 12-wk ADCS-ADL data already released), so I'm not too worried about when it comes. After all the cries of placebo effect last time, I get why they are waiting until the PK/PD data, showing correlation between 2-73 and efficacy, is ready this time, since the January release of five-week PK/PD data went overlooked after the big-spotlight November release of five-week safety and efficacy data.
The relevant, time-consuming complexity lies in the analysis performed via the NONMEM (and/or other) software, not in the data collected. While Part A complexity may make some difference, the NONMEM process takes months regardless of whether the data is from Part A or the more straightforward Part B.
Yes I initially overlooked that Week 1 of Part B would mark Week 6 of the trial overall, but then corrected myself. As we know, the company did undertake and report PK/PD analysis on the five-week results, but not until well after reporting week-five safety and efficacy data, at which time there was far less attention paid to the PK/PD data (which debunked the cries of placebo effect) than if it had all been released together. That is why the company is waiting until all the data are ready before releasing anything further for week 12 (which is actually week 17 of the trial as a whole). Of course we do have the interim ADCS-ADL data for week 12 already from the November data release.
Meant to say in last paragraph, because Anavex did NOT have week five PK/PD analysis ready. My bad.
Do more research, because PK/PD has lots to do with patient response. We have already seen this for 2-73 specifically in the company's January 11 PR, which reported that a PK/PD analysis of week five data (via linear regression analysis followed by bootstrap and Bayesian hierarchal analysis) showed statistically significant correlation between degree of improvement in MMSE and ERP scores and higher dosage of 2-73. The 30mg dose of 2-73 showed an 80% probability of boosting MMSE score by 2 points after just five weeks.
As Dr. Relkin puts it, "Evidence of a dose-response relationship is one of the factors taken into account by regulatory agencies when ultimately considering medications for approval."
One of the reasons you were not aware of the above is because Anavex did have the week five PK/PD analysis ready yet when it released week five data back in November 2015. By the time it did have the PK/PD data ready that debunked all the basher cries of placebo effect back in November, the spotlight was not nearly so bright. That is why this time Anavex will wait until week twelve PK/PD data is ready as well before it releases week twelve efficacy data.
Of course not, and I need to correct myself slightly, because week 5 data did go through PK/PD analysis, but it was released after the safety and efficacy data. That was the dose-response analysis that was reported recently and showed statistically significant correlation between level of 2-73 dosage and MMSE/ERP scores.