AI
Wednesday, August 18, 2021 10:42:28 AM
Where is the PDD Data?
It is likely Anavex anticipated full data to be finished by the end of 2nd quarter 2021; however, genomic sequencing probably surprised the company who’s now fashioning this intelligence into a robust data package for regulators. The company may have also deemed it valuable to wait to encompass 48-week OLE data as well.
There are at least five pieces of critical evidence to support this hypothesis:
- Anavex promised full data by end of second quarter - which has not fully transpired.
- Christopher Missling mentioned that the genomic data is being finalized and compiled only recently at the 3rd quarter 2021 conference call.
- The EU trial registry revealed Lewy Body as an ENROLLED subtype for the PDD OLE but NOT the original PDD trial.
- Slide 26 of the 6 Nov 2020 CTAD presentation reveals a detailed description of how Anavex is breaking the mold in precision medicine and mentions Lewy Body.
- At the 3rd quarter 2021 conference call, the planned preventative trial is alluded to be CNS-wide. This would include disorders like Alzheimer’s disease, PDD, and lesser-known CNS subtypes like Lewy Body.
To expand the discussion on slide 26, Anavex notes PDD as a “highly heterogeneous” disorder (like Alzheimer’s), indicating a wide range of root causes and great number of disease pathologies. Dr. Missling also mentioned this in one of their more recent conference calls, describing Blarcamesine’s wide-reaching therapeutic effect as exceptionally curious considering the varying degrees and pathologies of the disorder. He went on to summarize our data as curious considering multiple recent big-pharma failures in the PDD arena.
The “highly heterogeneous” nature of PDD and overwhelming cognitive/motor endpoint success makes the breakout of genomic data extremely important to future success in the PD and PDD trials, not to mention possible BTD with a data-rich package.
Slide 26 reveals exactly how Anavex is achieving this goal. They are identifying and breaking out sub-groups for key biomarkers/genes which are known to relate to PDD, Alzheimer’s disease, Lewy Body, and other extremely similar CNS disorders. It is evidenced in the EU OLE registrar that Anavex was able to determine at least part of their PDD cohort was mis-diagnosed, and actually have Lewy Body. Anavex is enjoying auxiliary cognitive/motor data towards the Lewy Body subtype in their PDD trial, which likely helped prompt the CNS-wide preventative trial. A 95% rollover rate for the AD 2b/3 trial, overwhelming PDD trial success, auxiliary Lewy Body subtype success (assumed), low-dose adult Rett success, and a slew of preventative preclinical trials in Blarcamesine and general S1R agonists can all be tied together to establish the grounds for a CNS-wide preventative in-human trial.
As Anavex integrates the RNA and DNA sequencing, they are actively finding meaningful patterns. Patterns which are revealing understanding of gene-dependent dose response, individualistic outcome response (sleep problem improvement vs. motor improvement vs. cognitive improvement, etc.), impact of Blarcamesine depending on existing medical regimen, and even response based on an individual’s environmental factors or historical indicators (someone who worked their life in a chemical factory vs. a salesmen or low/high income). Once completed, Anavex will be able to provide regulators a definitive analysis of which kinds of people respond the absolute best to the drug, which respond moderately, and who responds worst. We must remember that for the PDD trial, all patients performed better than SOC.
According to a cursory search, full genomic sequencing can take around 15 days per patient. In addition, KEM analysis provided by Ariana would need to be performed to automatically determine meaningful relationships in the data and quantify that for Anavex’s package. The comparative analysis would take additional time to collect and compile.
Summary: The way that Anavex has been processing data is cutting edge and unprecedented in the CNS space. This was initially what drove intrigue by the likes of Harald Hampel and other experts like Walter Kauffman. Anavex is likely polishing their package for regulators and in my opinion will see BTD. Even without a BTD grant, Anavex will have exponentially increased their chances of success in the upcoming 2b/3 PD and PDD trials, as well as the preventative CNS disorder trial. It is unknown currently whether Anavex is including OLE data in their final package. If so, items of particular interest are REM sleep improvement, further prevention or improvement, and gut microbiome analysis. In the PDD trial, 50% of dosed patients went from ‘disturbed sleep’ to ‘undisturbed sleep’ in 8 weeks. With such a short trial, it seems likely this number would increase somewhat as time continues.
To finalize the importance of what has been accomplished here, I leave you with a quote from Dr. Jaime Kulisevsky Bojarski, MD, PhD, Full Professor of Neurology & Vice-Dean Faculty of Medicine Autonomous University of Barcelona and Director of the Movement Disorders Unit, Department of Neurology, Saint Pau Hospital and Principal Investigator for the PDD trial, “As the first double-blind trial of Anavex 2-73 (Blarcamesine) in PDD, this proof-of-concept study provides extremely encouraging data. PDD can be debilitating with significant co-morbidities. New therapies are urgently needed to alleviate this suffering and disability. There has not been a mechanistically novel medicine (disease modifying) medication approved for PDD in over 20 years.”
https://www.anavex.com/wp-content/uploads/2020/11/CTAD-Anavex-PDD-001-Topline-data-Presentation-2020.pdf
It is likely Anavex anticipated full data to be finished by the end of 2nd quarter 2021; however, genomic sequencing probably surprised the company who’s now fashioning this intelligence into a robust data package for regulators. The company may have also deemed it valuable to wait to encompass 48-week OLE data as well.
There are at least five pieces of critical evidence to support this hypothesis:
- Anavex promised full data by end of second quarter - which has not fully transpired.
- Christopher Missling mentioned that the genomic data is being finalized and compiled only recently at the 3rd quarter 2021 conference call.
- The EU trial registry revealed Lewy Body as an ENROLLED subtype for the PDD OLE but NOT the original PDD trial.
- Slide 26 of the 6 Nov 2020 CTAD presentation reveals a detailed description of how Anavex is breaking the mold in precision medicine and mentions Lewy Body.
- At the 3rd quarter 2021 conference call, the planned preventative trial is alluded to be CNS-wide. This would include disorders like Alzheimer’s disease, PDD, and lesser-known CNS subtypes like Lewy Body.
To expand the discussion on slide 26, Anavex notes PDD as a “highly heterogeneous” disorder (like Alzheimer’s), indicating a wide range of root causes and great number of disease pathologies. Dr. Missling also mentioned this in one of their more recent conference calls, describing Blarcamesine’s wide-reaching therapeutic effect as exceptionally curious considering the varying degrees and pathologies of the disorder. He went on to summarize our data as curious considering multiple recent big-pharma failures in the PDD arena.
The “highly heterogeneous” nature of PDD and overwhelming cognitive/motor endpoint success makes the breakout of genomic data extremely important to future success in the PD and PDD trials, not to mention possible BTD with a data-rich package.
Slide 26 reveals exactly how Anavex is achieving this goal. They are identifying and breaking out sub-groups for key biomarkers/genes which are known to relate to PDD, Alzheimer’s disease, Lewy Body, and other extremely similar CNS disorders. It is evidenced in the EU OLE registrar that Anavex was able to determine at least part of their PDD cohort was mis-diagnosed, and actually have Lewy Body. Anavex is enjoying auxiliary cognitive/motor data towards the Lewy Body subtype in their PDD trial, which likely helped prompt the CNS-wide preventative trial. A 95% rollover rate for the AD 2b/3 trial, overwhelming PDD trial success, auxiliary Lewy Body subtype success (assumed), low-dose adult Rett success, and a slew of preventative preclinical trials in Blarcamesine and general S1R agonists can all be tied together to establish the grounds for a CNS-wide preventative in-human trial.
As Anavex integrates the RNA and DNA sequencing, they are actively finding meaningful patterns. Patterns which are revealing understanding of gene-dependent dose response, individualistic outcome response (sleep problem improvement vs. motor improvement vs. cognitive improvement, etc.), impact of Blarcamesine depending on existing medical regimen, and even response based on an individual’s environmental factors or historical indicators (someone who worked their life in a chemical factory vs. a salesmen or low/high income). Once completed, Anavex will be able to provide regulators a definitive analysis of which kinds of people respond the absolute best to the drug, which respond moderately, and who responds worst. We must remember that for the PDD trial, all patients performed better than SOC.
According to a cursory search, full genomic sequencing can take around 15 days per patient. In addition, KEM analysis provided by Ariana would need to be performed to automatically determine meaningful relationships in the data and quantify that for Anavex’s package. The comparative analysis would take additional time to collect and compile.
Summary: The way that Anavex has been processing data is cutting edge and unprecedented in the CNS space. This was initially what drove intrigue by the likes of Harald Hampel and other experts like Walter Kauffman. Anavex is likely polishing their package for regulators and in my opinion will see BTD. Even without a BTD grant, Anavex will have exponentially increased their chances of success in the upcoming 2b/3 PD and PDD trials, as well as the preventative CNS disorder trial. It is unknown currently whether Anavex is including OLE data in their final package. If so, items of particular interest are REM sleep improvement, further prevention or improvement, and gut microbiome analysis. In the PDD trial, 50% of dosed patients went from ‘disturbed sleep’ to ‘undisturbed sleep’ in 8 weeks. With such a short trial, it seems likely this number would increase somewhat as time continues.
To finalize the importance of what has been accomplished here, I leave you with a quote from Dr. Jaime Kulisevsky Bojarski, MD, PhD, Full Professor of Neurology & Vice-Dean Faculty of Medicine Autonomous University of Barcelona and Director of the Movement Disorders Unit, Department of Neurology, Saint Pau Hospital and Principal Investigator for the PDD trial, “As the first double-blind trial of Anavex 2-73 (Blarcamesine) in PDD, this proof-of-concept study provides extremely encouraging data. PDD can be debilitating with significant co-morbidities. New therapies are urgently needed to alleviate this suffering and disability. There has not been a mechanistically novel medicine (disease modifying) medication approved for PDD in over 20 years.”
https://www.anavex.com/wp-content/uploads/2020/11/CTAD-Anavex-PDD-001-Topline-data-Presentation-2020.pdf
