Natixis Bleichroeder on aab-001 Phase 3 "NTB_Test" issue.
Natixis Bleichroeder, Corey Davis - Buy, $31
NTB Is Indeed To Be
-Conducted a call with Dr. Lon Schneider, a neurologist with expertise in Alzheimer's, to compare two Alzheimer's ratings scales: ADAS-cog and the NTB
-A major concern has been whether the NTB is a validated test, given that the FDA has never yet approved a drug with NTB as the primary endpoint
-Think the Street questions the validity and potential acceptance of the NTB as a true outcome measure for Alzheimer's trials, as it was constructed by Elan and Wyeth and is a crucial efficacy measure in the Bapineuzumab program (and potentially in all other Alzheimer's programs)
-Do not think there is any foul play such as to deceive the regulatory agency and medical community with an outcome measure that would favor the companies' clinical programs
-It's not unusual that a pioneer in the field - like Elan is in Alzheimer's - should try to advance the science and further improvements
-According to Dr. Schneider, the NTB is not a new and strange concoction; it is an off-the-shelf battery of tests that belong to the basic toolbox of elementary neuropsychology, and, as such, he believes experts already accept its legitimacy as a valid scale in Alzheimer's
-While he can not predict what the position of regulatory agencies (FDA and EMEA) will be, he has high confidence that they will accept it as legitimate
-Know that the FDA division head, Rusty Katz, is well informed about the scale and fully briefed on the protocol
-In Dr. Schneider's view, an advantage of the NTB is that it is more sensitive than the ADAS-cog in measuring functional changes in mild Alzheimer's patients, especially with respect to executive function
-The fact that the reported value for the NTB will be a small number should not be surprising, according to Schneider; this is typical of neuropsychological tests, as raw scores from these are converted to a z-score, a standard deviation unit
-As a crude approximation, a 0.2 to 0.3 change (placebo subtracted) on the NTB could represent a 2 to 3 point change on the ADAS-cog
-Have been trying to emphasize that, with only 30 patients per arm, even a large effect size might not show statistical significance due to the inherent variability and high standard deviations
-There is a reasonable chance that there will not be across the board statistical significance on either NTB or ADAS-cog in the Phase II given the small patient numbers, but this did not concern Dr. Schneider at all
-For the Bapineuzumab Phase II, he thinks clinical relevancy would be a better measure
-There could be statistical significance when all of the arms are combined, but this was not discussed on the call
-Schneider pointed out five ways that could indicate the disease-modifying effect of a compound:
1) Different and divergent slopes between the placebo and treated arms - this is the EU requirement, according to Elan. However, the U.S. officials do NOT require a difference in slope - only that the effect difference be statistically different out to 18 months
2) A high degree of correlation between the cognitive and functional endpoints
3) An improvement in biomarkers such as abeta and tau in the CSF
4) A determination in brain volume by MRI
5) A correlation of plaque diminution with PET scanning using the PIB marker
-Remain very optimistic for a positive outcome from the Phase II results but want to set expectations appropriately when it comes to statistical significance
"....on the biotech battle-field, you need some élan...."
