Analysis of slides to date
This is my analysis of the slides tweeted by Edny Inui (@BMTEdny) from Anavex’s November 7th presentation of the A2-73 Phase 2a Part A top-level results and Part B interim results.
Conclusion: Today’s positive report confirms the results in the interim report of July 22, and A2-73 is still the most promising AD drug candidate. If the results hold up in the next trial, FDA approval is extremely likely.
Summary: Decades of brain degradation will not be completely reversed in a few weeks, but A2-73 appears to rapidly begin important improvements, much more than any alternative. A2-73 is still the best candidate to treat AD, and the outlook for eventual FDA approval is still very strong. This is what I hoped for and expected.
Possible Market Reaction: The news from today is even better than the news from July 22nd, but sometimes companies report good news and their price drops anyway, and there are evil people who appear to want A2-73 to fail, who are already trying to discredit these top-level trial results. Many people may still be scared due to the sharp drop this past week, and there are many people who do not perform due diligence and make investment decisions based on headlines. There are even morons who care what people like Martin Shkreli think.
Will intelligence win the day on Monday? I suspect so based on the parts of the presentation I have seen, but I think the PR on Monday morning may be a bigger factor than the presentation data for many investors. These new results show a very successful phase 2a Part A trial, and Part B interim results that are promising. This continues to make Anavex the top investment for Alzhiemer's in my assessment, and I still want every share I can get.
Notes:
Part A was 36 days, with 12 days of A2-73 administered, then 12 days off in a washout period, then 12 days on again. Results listed as Week 5 are at the end of Part A and covers all 32 patients, but only with 24 days of dosing, and only 12 days of steady, non-optimized dosing prior to end of Part A (5-week) assessments.
7 of 32 trial patients were not on donepezil or other AChEI; 25 of 32 trial patients were on donepezil or other AChEI; Therefore, 78% of the metrics are of patients already taking donepezil or equivalent, so improvement in these patients is an improvement over donepezil. Those numbers are not broken out in the tweeted slides, but this is only top-level data.
Some slides footnote "p = not significant. Trial was not designed to capture statistical significance of cognitive endpoints." This is NOT saying that stats were computed and found to be insignificant. This is only saying the statistical significance for subjective metrics is unknown at this time, due to this trial being open-label and impossible to determine for subjective measures, as is normal for phase 2 trials. Statistical significance (or lack thereof) of subjective metrics must be determined in a phase 3 double-blind, placebo-controlled trial. It appears Anavex is ready to begin phase 3 before the end of this year, according to one of Dr. Inui’s tweets, which fits with previous presentations that mentioned a 2nd IND before year end.
SECONDARY OUTCOME METRICS
Minor Metrics
1. Pharmacokinetic (PK) blood sampling, measuring absorption, distribution, etc.
2. HAM-D, only scored at baseline
3. RM/HIS10, only scored at baseline
Major Metrics at the end of Part A
(After only 12 days steady non-optimized dosing with A2-73)
1. EEG/ERP (at end of Part A)
This is an objective measurement of a brain wave.
“Anavex 2-73 Reverses Cognitive Deficits Measured by Standard ERP Methods at Week 5”
Again, this is after only 24 non-optimized doses, and only 12 sequential doses prior to the test.
• P300 Amplitude: Improved 80%
• Reaction Time (latency): Improved 66%
• Task Accuracy: Improved 85%
• False Alarms: Improved 104%
2. MMSE (Mini-Mental State Examination) (at end of Part A)
This is a 30 point questionnaire that is subjective when not in a double-blind, placebo-controlled trial.
The MMSE inclusion criteria for patients in this trial was 16-28.
Result: Improved 1.5 pts (approximately 20.5 to 22)
3. ISLT (International Shopping List Task) (at end of Part A)
This is a verbal learning assessment.
• ISLT accuracy: Improved .09
• ISLT time: Declined .22
4. Cogstate Brief Battery (CBB) (at end of Part A)
The unit of measure appears to be Dunlap’s d. My categorization of the scores is based on that.
• Detection Task (psychomotor speed): Improved .33 (moderate improvement)
• Identification Task (visual attention): Improved .44 (moderate improvement)
• One Card Learning Task (visual memory/learning): Improved .10 (minor improvement)
• One Back Task (working memory): Improved 1.10 (very large improvement)
Major Metric at Part B’s first milestone
ADCS-ADL (Alzheimer's Disease Cooperative Study - Activities of Daily Living)
These are interim Part B results at Week 12 (3 months), with 14 patients completing so far. This is a subjective assessment of how much help an Alzheimer's patient needs to eat, walk, bathe, get dressed, watch tv, etc. Like MMSE, it needs a phase 3 for statistical significance to be ascertained. It uses a 0-78 scale (although at least one source uses 0-30 scale). Results are compared to the baseline of Part B, not the baseline of Part A.
Result: 11 of 14 patients (78.6%) improved 3.21 pts, from approximately 64 to 66.2.
Final notes excerpted from slide 17
• This evidence provides sufficient confidence to start a larger randomized, double-blind Phase 2/3 study
• Additional data, including updates on Part B to be presented at future scientific meetings
