An outstanding post by amstocks82 on IV late yesterday... A helpful chart didn't transfer during the copy / paste.
"Trial data and comparisons
Clinical trials data for Anavex Alzheimer's trial:
Current Primary Outcome Measures:
ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) [ Time Frame: 48 weeks ]
Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog)
Result:
ANAVEX®2-73 treatment slowed cognitive decline by 45% compared to placebo at 48 weeks.
Mean difference in ADAS-Cog score change of -1.85 points.
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ADCS-ADL (Activities of Daily Living) [ Time Frame: 48 weeks ]
Reduction in decline of the ability to perform daily activities assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Activities of Daily Living Scale (ADCS-ADL)
Result:
ANAVEX®2-73 treatment was 167% more likely have improve function compared to placebo, at clinically significant ADCS-ADL score change of +3.5 points or better at 48 weeks.
Clinically significant response categorization in function defined as ADCS-ADL ≥ +3.5-point change from baseline.
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Current Secondary Outcome
CDR-SB (Clinical Dementia Rating Scale Sum of Boxes) [ Time Frame: 48 weeks ]
Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared with placebo using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)
Result:
ANAVEX®2-73 treatment slowed clinical decline in cognition and function assessed by 27%.
compared to placebo, ANAVEX®2-73 treatment difference in mean score change of -0.42 points.
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Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 48 weeks ]
Assess the safety and tolerability of ANAVEX2-73 compared to placebo
Result:
Similar TEAE rates in Active and Placebo arms.
Adverse Events ≥7.5% were predominantly mild or moderate.
No clinically significant changes in vital signs, lab values and ECG parametersin Active and Placebo groups.
Dizziness consistent with CNS drug effects. Will be mitigated in the future by bedtime dosing.
Safety findings are consistent with the known safety profile of ANAVEX®2-73.
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Current Other Pre-specified Outcome Measures
No results announced yet for the following other measures.
Number of participants with change of brain volume assessed by MRI [ Time Frame: 48 weeks ]
To evaluate the effect of ANAVEX2-73 on structural and Arterial Spin Labeling (ASL) MRI scan assessments characteristic for AD pathophysiology compared to placebo over a 48-week treatment duration
Blood assessment [ Time Frame: 48 weeks ]
Blood assessment from baseline and compared to placebo at +48 weeks: Abeta40, Abeta42, T-tau, NFL, YKL-40, BACE1 concentration
CSF assessment [ Time Frame: 48 weeks ]
Changes in CSF parameters (Abeta40, Abeta42, T-tau, P-tau, NFL, YKL-40, neurogranin, BACE1 concentration) characteristic for AD pathophysiology from baseline and compared to placebo at +48 weeks treatment differences within subgroups will be performed
Number of participants with pre-specified genetic variants [ Time Frame: 48 weeks ]
AD relevant pre-specified genetic variants will be assessed. Statistical testing of treatment differences within subgroups will be performed
RSCAQ sleep score [ Time Frame: Weeks 0, 4, 12, 24, 36, and 48 ]
To evaluate whether ANAVEX2-73 improves sleep continuity as assessed on a serial basis (weeks 0, 4, 12, 24, 36, and 48) with a questionnaire that assess reported sleep continuity (RSCAQ)
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Additional information from the trial data released to date:
Overall, the ADAS-Cog group treated with Anavex 2-73 improved by -1.85 points over the untreated placebo group. Or another way to put it is that the placebo group declined over 48 weeks by 4.11 points and the Anavex 2-73 group declined by 2.26 points. But the surprising thing that they wrote is: "Among patients, who improved with ANAVEX®2-73 treatment, Mean ADAS-Cog score improvement -4.03 points."
This implies that the treatment group has many that don't respond very much. For the Parkinson's group, it was found that the 30 mg group didn't respond very much but the 50 mg group did.
What could cause a good percentage of the trial group to have 4.03 improvement over the placebo group but the average of the treatment group only improves over the placebo group by 1.85?
In this test, given that the groups are randomly selected (double blind), there are 1/3 started with the placebo, 1/3 with the 30 mg dose and 1/3 with the 50 mg dose. There are also ~20% of people who have a gene mutation that causes them to not respond as much from Anavex 2-73.
Assume that the Alzheimer's patients respond similarly as the PDD patients. Since 169 started with 30mg dose, with 20% having the gene mutation, 135 respond slightly better and 34 (the 20% with the mutation) respond less well. So, perhaps no noticeable response. In the 50 mg dose group, 135 respond well to the drug, 34 with the gene mutation don't respond as well but may have some effect. This would mean at the start, they have initially 338 in the treatment group but only 135 are high responders. (These numbers are initial before dropouts.) This means about 40% are in the group that are likely to be high responders due to the 50mg dose and not having the mutated gene that impacts effectiveness of Anavex2-73. But in that 135-person group of potential high responders, some may be impacted by other factors that reduce the effectiveness as seen by the scoring. I.e., elderly patient scores can be heavily impacted even by the time the testing is done. It works out that if 100 patients are high responders and improve by 4.03, and on average the others in the treatment group improve by 0.9, then the average comes out to around 1.85 improvement over the placebo group.
Why do these calculations? I'm trying to see if the results from the Alzheimer's trial line up with the PDD trial, RETT trial and prior Alzheimer's trial with respect to the effectiveness of the drug. My view has been that Anavex 2-73 is not actually an Alzheimer's drug in that it targets Alzheimer's disease. I think of it as a drug that increases overall cellular health. Some age-related diseases occur due to cellular health declining as part of the aging process. If cellular health is improved by a drug like Anavex 2-73, diseases like Alzheimer's or Parkinson's improve or perhaps in some cases go away.
What the above implies is that Anavex 2-73 is really a drug to help with all types of age related diseases and conditions where cellular health is reduced such as RETT syndrome or Fragile X. It also means that Anavex 2-73 can be given at the same time as many other drugs. This makes Anavex 2-73 a potential blockbuster of enormous potential."
