The Press Release state basic facts in points:
Q: Who are study participants? A: 20 patients in all cohorts.
Discussion: When you are an engineer they tell you to check the quality of large population of parts by drawing at random sample size of at least 30 parts from given batch. I worked for Dental X-ray equipment manufacturer who recommended smallest sample size for clinical test to be 30 patients. At 20 we are not exactly ready to validate the 80/20 break down in general population by Phase 2a study. Stay tune to Phase 2b/3.
Q: Who are ANAVEX 2-73 Responders? Here we have to turn to the part of PR given here:
A: ANAVEX 2-73 Responders are (by definition):
- Milder disease patients (baseline MMSE>=20)
- Average (?) MMSE +2.0 MMSE and +4.9 ADCS-ADL
Discussion: Point 1 makes of all those who were called ANAVEX 2-73 Responders i.e. included in the definition are all Responders in High Concentration Cohort but (at 57 weeks) but they are not limited to members of only High Concentration Cohort (1011 & 1009):
To further cull the herd I applied the conditions for average +2.0 MMSE and +4.9 ADCS-ADL and tried to pick and match the patients to these metrics. See CTAD Presentation from Nov. 2017. The final set was not a perfect match but close enough. It was 3 patients: 2010, 2006 & 1013. Their averages give +4.8 ADCS-ADL and +2.9 MMSE.
Further on 1013 deteriorates after 57 weeks going onto 109 weeks ( -4.0 MMSE & -16 ADCS-ADL), but 2010 & 2006 improve (+3.0 MMSE and +0.0 ADCS-ADL).
The sample size is too small to have definitive iron clad trend as one measure of improvement only partially confirms the results of other. That is why the 148 weeks data by the virtue of “demographics” alone (number of patients staying with the study or not deteriorating) can be revealing of expected future trend in Phase 2b/3. Vaguely, these probabilities for patients in natural course of the disease and predicted for Phase 2b/3 might be relevant and give insight but with the heterogeneity of humans the results from Phase 2a (148 weeks) and by extension Phase 2b/3 might differ to a degree.
Probabilities for a AD patient to find himself/herself in one of four classes on timeline of 6 year in natural course of disease.
Notice that on purely demographic terms at 3 years population with No Decline practically disappears. Let’s see what Phase 2a 148 weeks data tells us.
The same for modeled Phase 2b/3 based on the very “imperfect” date released till now by the company and assuming The High Concentration Cohort is representative of general population.
On a second thought….
A similar combination of patients approximating the parameters given for the ANAVEX 2-73 Responders can be made:
Patients: 2010, 2006 & 1014 (MMSE +2.2, ADCS-ADL +4.5). Patient 1014 is included in the Set A given above plot of MMSE scores for 109 weeks for High Concentration Cohort Responders.